KR20170097603A - Centralized framework for storing, processing and utilizing proprietary genetic data - Google Patents

Abstract

A system and method for performing a medical test is disclosed. The systems and methods allow the creation and use of medical tests. The system and method may provide for use of proprietary information in medical tests from a number of proprietary rights holders. The system and method allow for the protection of information of reason while allowing the user to receive test results. Also disclosed are systems and methods that facilitate detection of structural variations in gene sequences that can not be readily detected when genetic information is sequenced using short reading data. Systems and methods use covariant parameters to identify covariant parameters with structural variations that can not be easily detected and to determine the presence of structural variations.

Description

≪ Desc / Clms Page number 1 > PROCESSING AND UTILIZING PROPRIETARY GENETIC DATA FOR CENTRALIZED FRAMEWORK FOR STORING,

This disclosure relates to a method and system that facilitates the use of proprietary biomarkers among users and facilitates payment for intellectual property usage among users of systems and methods. The methods and systems of the present invention also provide genetic data that can be safely retrieved and interpreted to produce the results of a genetic test without the need to transmit a large genome file over the Internet.

Diagnostic tests employing the use of biomarkers are often protected by intellectual property rights in the form of generic patent claims or trade secrets when a method or patent is considered a qualifying subject. Often, identifying the presence of a particular biomarker does not necessarily require obtaining data or equipment from an intellectual property owner associated with the biomarker. For example, the presence or absence of a particular genomic mutation can be accomplished through the use of a multipurpose sequencing device or a gene chip.

As cost barriers become lower, the number of laboratory and clinical settings that can access equipment to determine genetic information and other biomarkers is increasing. Some companies and researchers have done research to determine the effects of some of these structural variations with unknown effects. This research requires a large amount of data and a large amount of money to implement. Researchers often do not want to reveal their test results, but instead will want to keep the crucial impact of genetic variation as confidential as the information on the reason. Although there are many data sharing services, many researchers choose not to submit data of this reason to data sharing services. As a result, only the individual or group conducting the study has the information necessary to determine the physiological effect of the mutation. In order to determine whether these mutations are present in the patient's germline DNA or somatic cell DNA of the tumor, the patient must submit the genetic test directly to the information owner. This makes genetic testing more diverse and data inefficient. Also, there is currently no way for a patient to perform a single gene sequencing and perform all relevant genetic tests on a single genome, resulting in increased likelihood of error.

Licenses for the use of intellectual property rights traditionally result from direct negotiations between the rights holder and one or more users or licensees. However, when many potential users or licensees exist in connection therewith, the transaction costs become enormous. This is particularly the case when potential users or licensees sometimes perform diagnostic tests related to certain intellectual property rights. Diagnostic services can also perform tests that produce a wide range of information, such as whole genome (WGS) or exome sequencing (WES) or genome-wide SNP analysis using gene chips, and are useful for diagnostic purposes A wide range of potential cause markers may be disclosed. However, the individual or organization performing the diagnostic service does not know how the generated information can be used by other parties or which intellectual property rights may be involved. A further problem is that a given diagnostic test may require the evaluation of a biomarker that may be covered by a number of patents or trade secrets belonging to a number of other rights holders. Obtaining a comprehensive profile of the biomarkers associated with a particular condition can involve a number of other entity-owned patents, which can result in significant transaction costs for directly licensing the relevant intellectual property rights.

The need to negotiate and manage a large number of licensing agreements hinders potential users or licensees from respecting the intellectual property rights of patent holders. Alternatively, the need to manage a large number of licensing agreements may hinder the use, development and / or verification of biomarker-based diagnostic techniques in situations where it is difficult to determine all rights holders that may be involved. This challenge has been recognized as creating "patent bushes" in which the commercial activity or legal compliance of an area is hampered by "thickets" of patents controlled by several different entities.

Since private genetic information can be intercepted by others, transmission of genetic data over the Internet poses a security problem. In addition, the entire genome, or even a portion of the genome, is a very large file that requires a large amount of bandwidth and memory for transmission and storage. Thus, there is a need for a system that can retrieve and interpret gene data to generate genetic test results without having to transmit large genome files over the Internet.

Finally, scanning, interrogating, and storing patient gene data can be performed with next-generation sequencing, or exome, technology, coupled with electronic health records and associated decision support tools. However, the absence of a single "point of truth" for gene data stored, queried, interpreted and accessed on demand reduces accuracy and increases medical errors. Without a standard personal genetic data source, several laboratories can perform sequence queries on a patient's gene sequence and conclude different results with potentially dangerous results. While it is important to distribute the patient's genomic profile to providers, ordering data electronically through various enterprise-based systems is inherently a safety, security and liability issue. Regulatory monitoring is being strengthened and can be expected to increase. In addition, intellectual property owners may not be aware of and / or be compensated for the use of their patents and know-how in distributed systems.

Thus, there is a need for genetic testing that utilizes in-silico testing to speed up genetic testing and reduce costs while providing diverse genetic tests from a single sample. There is a further need for a system that can detect such mutations through parameterization of other mutations or markers in a co-variant gene sequence with large insertions or deletions. Therefore, there is a need for a system capable of detecting mutations or other biomarkers present in somatic cell cancer cell DNA. There is a need for a system that can simplify sample and data analysis to improve the accuracy of mutation detection in somatic cell cancer DNA. There is also a need for a system that can identify some or all of the identified important mutations that may be present in tumor cells, in which the tumor cell DNA is sequenced using next generation sequencing techniques.

Therefore, there is a need for a single system that allows the holder of the proprietary medical information to perform tests on the patient's genetic information or other medical information without having to disclose the proprietary information to the third party. There is a need for a system that allows the proprietary medical information owner to upload this information for medical testing purposes without fear of having to disclose it to the public as a whole.

A system is provided that facilitates the use of proprietary biomarkers in genetic testing, and analyzes and notifies the results of genetic tests. The system may include a control server coupled to the remote application, wherein the remote application is configured to obtain a result of the genetic test. The control server may also be connected to a record database of reasons, including a record of the biomarkers of reason and rights holders of the biomarkers of reason. A gene data storage server containing genetic information for one or more patients can communicate with a remote application. The remote application may be configured to send and receive data to perform genetic testing. The control server may be configured to send and receive data to account for payment from the payer party to the rights holder. The control server may also be configured to account for payment from the payer party to the owner of the gene data storage server. The system may include a black box containing information of the reason for being encrypted to perform the genetic test.

The remote application can be located with the cloud's genetic data storage server. The remote application may be configured to receive data from the gene data storage server and perform genetic testing. Alternatively, a third party scanning application can perform genetic testing. A request for a genetic test may be initiated by the control server, or initiated by a third party scanning application. The control server may describe the payment to the third party and / or the rights holder from the party of the payer, or to the rights holder from the third party. The third party scanning application may be located with the gene data storage server.

The data storage server and the gene data interpretation server may be selected from any one of a server, a cloud, or a web hosted data store. The remote client and control server may be selected from any one of a server, a cloud, or a web hosted application. The connection may be selected from any one or more of TCP, UDP, VPN, SQL, socket or OS messaging or other known connection technologies, but is not limited thereto. Those skilled in the art will also appreciate that any current, future equivalent protocol suitable for transmitting secure and non-secure information between two co-located or non-co-located software instances is contemplated by the present invention.

Methods are provided to obtain genetic tests and to account for payments to rights holders. The method may include obtaining gene utilization information from the payer party. The method also includes a record database of reasons, and the record database of this reason may include a record of the proprietary biomarker and the rights holder of the biomarker of reason. The biomarker required for genetic testing can be determined and the payment to the rights holder can be described. The genetic test may be performed by a remote application, or may be performed by a third party scanning application.

The gene utilization information may include a prescription for genetic testing, a biomarker to be searched during genetic testing, and / or a portion of the genome to be scanned during genetic testing.

A license for the use of a proprietary biomarker may be obtained before or after a request for a genetic test is generated. Such an application may be sent to the scanning party to perform the test. The system and method may account for the payment of royalties or licensing fees associated with biomarkers.

The system may also include a known biomarker to determine a test for a new biomarker based on the results obtained from the test. Patients who are tested for a particular disease can be subdivided into subgroups and the genetic information of each subgroup of patients is searched to determine correlations at various genetic sites for the disease.

In certain embodiments of the present invention, a method includes receiving a request over the Internet to identify structural variations on a gene sequence stored on a genetic server; Querying for a gene sequence - the gene sequence is obtained from short reading data; Using one or more parameters that are covariate with structural variations to identify structural variations; And returning results over the Internet. The method can detect structural mutations that increase the risk of any one or more of cancer, cardiovascular disease, neurodegenerative disease, mood disorder, or any Mendelian genetic disease.

In certain embodiments, the parameters that are covalent with the structural variation can be deletion, replication, copy number variation, insertion, inversion, and translocation.

In certain embodiments of the invention, the structural variation can be selected from the group consisting of insertions, deletions, mutations, translocations, and replication number variations. In certain embodiments, the structural variation may comprise at least 100 base pairs. In certain embodiments, the structural variation may comprise at least 1000 base pairs.

In certain embodiments of the invention, a request to identify a structural variation may be received from the patient's electronic health record or electronic medical record.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a schematic diagram of a system for facilitating the use of proprietary biomarkers among users and facilitating payment for the use of intellectual property rights among users of the system.
Figure 2 illustrates the functionality of the user interface of the system.
Figure 3 shows a flow chart for querying the system for the presence of a biomarker of interest in a patient record.
Figure 4 illustrates an exemplary relational database structure for a system to facilitate use of proprietary biomarkers among users and facilitate payment for intellectual property usage among users of the system.
5 illustrates an exemplary hardware implementation for implementing the methods described herein.
Figure 6 illustrates an exemplary large-scale hardware implementation for implementing the methods described herein.
Figure 7 shows an overview of the system for providing biomarker test results.
Figure 8 illustrates a gene testing and notification system in accordance with one embodiment of the present invention.
Figure 9 illustrates the interaction of a server and a database in accordance with an embodiment of the present invention.
Figure 10 illustrates the interaction of a database with a server including a third party request application.
Figure 11 shows a gene test and notification system comprising a plurality of gene data storage servers and a plurality of test request sources.
Figure 12 shows a gene test and notification system with multiple gene data storage servers and a third party request application.
Figure 13 shows a biomarker accounting system for a genetic test and a proprietary third party requesting and performing genetic testing.
Figure 14 shows a biomarker accounting system for gene testing and thinking where the control system initiates a request for a genetic test and a third party performs a genetic test.
Figure 15 shows a biomarker accounting system for gene testing and thinking where the control system initiates a request for genetic testing and the same system performs genetic testing.
16 shows a medical test system using information of reason.
Figure 17 shows a non-limiting example of encryption of a gene sequence.
Figure 18 shows a method of using an encoded gene sequence in a genetic test by encoding a patient gene sequence.
19 illustrates a method of using an encoded gene sequence in a genetic test by decrypting the gene sequence for comparison.
Figure 20 illustrates an implementation of a medical test system configured to test using information of reason.
Figure 21 illustrates an implementation of a medical test system configured to perform a number of tests using information of reason.
Figure 22 illustrates a non-limiting embodiment illustrating the payment based on a medical test using information of reason.
Figure 23 illustrates an embodiment for performing genetic testing using a standalone software application.
Figure 24 shows an embodiment using an encrypted medical test.
Figure 25 illustrates an embodiment using an encrypted medical test by an external biomarker server.
Figure 26 illustrates the use of a genetic testing system in which a third party performs gene sequencing and biomarker studies.
Figure 27 illustrates the use of a genetic test system in which different parties perform gene sequencing and biomarker studies.
Figure 28 illustrates the use of a genetic test system for a patient who has already been sequenced with the genome.
Figure 29 shows a flow diagram of a method for generating a biomarker script and performing a scan of the genome.
30 shows a screen shot of an exemplary prescription generation interface.
Figure 31 shows a screen shot of an exemplary interface while patient information is acquired and scanned.
Figure 32 shows a screen shot of an exemplary result of a scan for a patient without a defined gene mutation.
Figure 33 shows exemplary results provided for a scan of a patient having a portion of a defined gene mutation.
Figure 34 shows an example of a gene mutation that can cause disease.
Figure 35 shows an example of a method for determining a parameter that is covalent with a large gene mutation.
36 is a flowchart showing a process of acquiring genetic information from a somatic cell cancer cell and querying it.
Figure 37 shows an overview of a system for obtaining, querying, and describing payment corresponding to a genetic test.
Figure 38 shows a system for obtaining a prescription for genetic testing from an electronic medical record and returning the results to an electronic medical record.

Justice

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the relevant arts.

The articles "a" and "an" refer to one or more than one (i.e., at least one) of the grammatical object of the article in this specification. By way of example, "an element" means one element or more than one element.

The term "administrator" or "administrator user" refers to one or more individuals or parties responsible for maintaining the health and availability of the systems and methods described herein.

The term "authority" refers to having the right to access certain information stored in the system or database.

The term "biomarker" refers to a characteristic in which a quantitative or qualitative characteristic is used to determine the biological condition or the presence or risk of a disease or condition, or a response to a treatment or drug. Biomarkers include, but are not limited to, genomic information directed by a sequence or presence of one or more nucleotide bases in a DNA molecule. Other non-limiting examples of biomarkers include single nucleotide polymorphisms (SNPs), replication number variations, insertions and deletions, haplotypes, genetic mutations, genetic linkage disequilibrium, Metabolic information, proteomic information, lipidomic information, and combinations thereof.

A "biomarker script" is a set of computer readable instructions that cause the system to scan a gene sequence for the presence of one or more particular biomarkers.

A "black box" refers to any combination of one or more of a computer, a server, a processor, an application or software that can prevent an unauthorized user from verifying information protected by a black box. Protected information may include algorithms, databases, data elements, data attributes, data features, data structures, and the like. Blackboxes can encrypt protected information to maintain the proprietary nature of information such as trade secrets.

The term "clinical parameter", "clinical data" or "clinical information" refers to physiological parameters or demographic parameters.

The term "cloud" refers to any shared pool of networks or servers.

The term "collocated" refers to two or more servers, databases, computers, software applications, or any other computing module in the same location. The same location can mean being located in the cloud behind the same server, virtual instance or computer, a single intranet or the same firewall. The term "co-located" may refer to two or more modules configured to transfer data between two or more modules without transmitting data over the Internet. The term "co-located" may also refer to two or more modules in which one of the modules is configured to be embedded in another module.

"Companion diagnostics" or "CoDx" is intended to indicate the intended use of a particular drug or drug sequence for a targeted patient group or subgroup, .

The term " comprising "includes, but is not limited to, anything following the word" comprising. &Quot; Thus, the use of this term indicates that a listed element is necessary or essential, and that other elements may be optional and may or may not be present.

The term " consisting of "includes and is limited to whatever follows the phrase" done ". Thus, this phrase indicates that a restricted element is necessary or necessary and that no other element can exist.

The phrase " consisting essentially of "includes any element listed after the phrase and is limited to other elements that do not interfere with or contribute to the initiation-specific activity or action of the listed element do. Thus, the above phrases may or may not exist depending on whether the listed elements are necessary or necessary and other elements are optional and affect the activity or action of the listed elements.

The term "control server", "control application" or "CS" refers to a server or application that is configured to communicate with another server, database, or application and to send and receive information from another server, database, or application.

The term "co-variant" refers to at least two parameters, wherein a particular variation of one of the parameters represents an increased probability of a particular variation of another parameter.

The term "diagnostic test" refers to any process performed on a biological sample that generates information referred to as "diagnostic information" for the sample. "Diagnostic information" may include, but is not limited to, genomic, proteomic, and lipidomic information related to standard blood tests for determining biological samples and blood chemistry.

The term "diagnostic information" or "original diagnostic information" refers to information generated from a laboratory or other test that includes biomarker information, and information about the biomarker may be tagged, There is no need to be.

The terms "demographic parameter", "demographic data" or "demographic information" are used to predict or determine the health status or risk of an individual's disease or condition that is not necessarily an individual's physical examination Quot; information " Non-limiting examples include, but are not limited to, history of personal or individual relatives, diet, exercise, lifestyle such as smoking drinking patterns or sexual activity, past medical procedures or medical devices such as pacemakers or stents, .

The term "database" refers to any organization of data or information that can be queried.

The term "diagnosis" or "Dx " refers to a test intended to determine a disease affecting a patient.

"Electronic health records" and "electronic medical records" are digitized versions of official health records for individuals.

The phrase "equivalent to a known diagnostic test" means that the biomarker script determines the presence of the same genetic mutation as in a known diagnostic test. In the case of a PCR-based test, this means that the biomarker script scans the genome for the same mutation for which the PCR-based test provides the probe. For enzyme-based tests, this means that the biomarker script scans the genome for a mutation of the gene that results in an enzyme level determined in a known test.

A "gene data interpretation server" or "GDIS" is a server or database containing instructions for interpreting genes or other biological data.

A "gene data storage server" or "GDSS" is a server or database containing genes or other biological data related to one or more patients.

"Genetic information" refers to any kind of data associated with one or more nucleotides. The nucleotide may comprise a point mutation, a whole genome sequence, or a whole exome sequence, or a moiety such as a target sequence at a particular location.

"Gene exploitation information" refers to the information needed to perform genetic testing. As used herein, gene utilization information may refer to a prescription for a genetic test, a biomarker to be retrieved during a genetic test, a related algorithm, and / or a portion of the genome to be scanned during a genetic test.

"Genetic testing" refers to any one of a neonatal screening diagnostic test, a carrier test, and a prenatal test. Genetic testing can identify suspected diagnoses, predict future disease potential, detect the presence of carrier status in uninfected individuals, and predict response to treatment or medication. Genetic testing can include identifying gene mutations, including, but not limited to, single nucleotide polymorphisms, copy number variations, insertions, deletions, and other known mutations. Genetic testing can include algorithms, decision trees, and statistical analysis.

"Germline DNA" refers to the intracellular DNA that is transferred to the next generation of cells.

The term "field" refers to the category of information entered into the database, and the field includes data of the same quality or type among the records.

The term "information " refers to any algorithm, script, association, or any other data that can be stored by a computer.

 A "prescription for testing" is a request by any party to retrieve or analyze biological information.

The term " record " refers to a data set present in a database associated with the same subject, such as a patient or biomarker.

A "remote client", "remote client application", "remote application", or "RCA" is an application that resides on a computer that can be virtually or physically separated using VMware. The remote application may be a personal area network, or a PAN, a local area network, or a LAN, a large urban network, or a MAN, a wide area network, or a WAN, or a storage area network, or a SAN, an enterprise private network, or any other general purpose network, such as an EPN, a virtual private network, or a VPN. The remote application sends and receives commands to interpret the data. Data may be genetic variation data, algorithms and the like that interpret gene data in accordance with instructions. Optionally, the remote application may be located with the gene data storage server as defined herein.

The term "risk factor " refers to a change in the probability that a patient will cause a disease based on a particular factor or factors. Risk factors can be expressed in multiples such as 1.2X, where the probability of a patient with a particular disease-causing factor is 1.2 times higher than the probability of a patient without a disease-causing factor.

"Short read data" refers to a portion of the genome of about 10 to about 100 basepairs.

A "structural variant" is a specific part of the genetic code, and some proportion of the population will have a different base pair sequence than the other part in that part. Structural variations include, but are not limited to, insertion of a base pair into a genetic code, deletion of a base pair from a genetic code, relocation of a base pair in a genetic code, replication of a portion of a genetic code, translocation of one or more base pairs, Or a mutation of one or more base pairs within a portion of the genetic code.

A "third party requesting application" is an application located with the gene data storage server and the remote client, allowing a test request to be made directly to the remote client.

The terms "diagnostic service provider", "diagnostic service provider user", and "diagnostic service provider user" refer to a party or organization performing a test or other laboratory task to generate information about the presence of a biomarker in a patient .

The term "payment " refers to the creation of a record detailing the obligations a user of a system or method described herein should pay to another user of the system or method described herein. The actual receipt of financial funds is not required to complete the "payment". Rather, financial funds can be escrowed by an administrator or other party that receives funds from a worker and holds it for the benefit of another user. Alternatively, the payment may be completed by updating the log, the database, or by sending a notice that the payment must be made to the other party from one party and later a transfer of financial funds may occur. However, "payment" may also occur when transferring financial funds from one user to another.

The term "physiological parameter "," physiological data "or" physiological information "refers to measurement of physiological function that is not necessarily limited to the quantitative or qualitative characteristics of a chemical and biomarker. Non-limiting examples include sex, age, height, weight, blood pressure, atrial or ventricular pressure, heart rate, pulse, blood chemistry, glomerular filtration rate (GFR), EKG data, PET data, MRI data, And other data representing the data.

The term "privacy rule " refers to a set of rules implemented to control the level of access or authority to information stored in a system or database.

The term "proprietary biomarker" refers to a biomarker associated with a particular intellectual property right, which provides a material composition for detecting a biomarker as well as a specific method for using, detecting or inducing information from the biomarker A patent application.

"Historical reasoning database" refers to data stored in a database owned by an intellectual property owner. A description of a reason may refer to a patent or trade secret.

"Restricting "," Restricting information "and like terms refer to restricting access to information stored in the system described herein or accessible to a particular user using the methods described herein.

The term "rights holder" or "rights holder user" refers to a user or a party who is the owner of an intellectual property right. For example, the systems and methods described herein provide accounting or payment for use of a subject within the intellectual property realm. "Rights" may include pending and granted patents and trade secrets, know-how and any other form of recognized intellectual property rights.

The term "payer party" or "payer party user" refers to an insurer or other party that is responsible for at least partial payment to other users of the systems and methods described herein. In addition to the insurance company, the payer parties may include patients who benefit from diagnostic services.

The term "patient" or "patient user" refers to an individual, person, or animal from which diagnostic information about the biomarker is collected.

The term "doctor" or "physician" means any biomarker identified for the purpose of performing a medical evaluation using the system or method described herein, or any license issued by a governmental authority, Refers to an individual using the system or method described herein for access.

The term "user " refers to any party or agent of the party transmitting or receiving information from the system described herein or by the methods described herein.

The term " table "refers to the organization of data within a database.

The term "foreign key" refers to a parameter acting as a restriction on data that can be entered on a database table.

The term "proteomic" refers to an amount, identity, primary structure (sequence of amino acid residues), pi (isoelectric point), or any other qualitative information associated with a protein present in a biological sample It refers to information about something.

The term " lipidomic " refers to information relating to any of the quantity, identity, chemical structure, oxidation state or any other qualitative information associated with the lipid present in the biological sample.

The term "patient identification information " refers to any data that contributes to the person ' s personal identity.

The term " relational database " refers to a database that can be queried to match data by common characteristics found in the data set.

The term "server" means any structure capable of storing digital information. As used herein, a "server" may also refer to a database, application, intranet, virtual instance, or other digital structure.

A privacy facilitating system for sending payments to rights holders

The systems and methods disclosed herein provide for linking patient and / or sample centered molecules, genes, or other biomarker data to information of reason useful for medical diagnosis or risk assessment. The described system can search multiple databases, indexes, catalogs, or databases in various languages to find patented or proprietary gene biomarkers and related information, populate and maintain the system database (s). Genetic biomarkers can include polymorphisms, chain imbalances of alleles at multiple loci, and mutations in genomic or mitochondrial DNA. The system may receive input from a third party database or a database from which a third party database can automatically upload genetic information for new reasons. The system database (s) includes proprietary genetic information and / or biomarkers, including owner information, clinical, diagnostic and therapeutic data. The system database (s) may additionally include an error log and / or an audit log for recording data inconsistencies in the system database (s). Those skilled in the art will readily recognize that the data structure for maintaining the database is not particularly limited, and can use, for example, a relational database management system or an object-oriented database management system. This application claims the benefit of US Provisional Patent Application No. 13 / 371,422, filed February 11, 2012, US Patent Application No. 14 / 452,979, filed August 6, 2014, US Patent Application No. 11 / And U.S. Patent Application Serial No. 14 / 511,293, filed October 10, 2014, the entire contents of which are incorporated herein by reference.

This study is for an integrated grant intended specifically for HBOC (Hereditary Breast and Ovarian Cancer) for all clinical genetic testing purposes. The framework, YouGene-Connect ™ (YG-C), is implemented on a cloud-based platform that centralizes the silico gene test to reliably detect genetic characteristics using a clinical-grade database. If a particular detection technique, mutation, and variant classification is reasoned, this neutral platform enables the use of gene-related IP rights that are important to foster and implement innovation. This demand has been exacerbated by recent Supreme Court rulings depriving patent patents of intellectual property (see Myriad, Prometheus). For protection, the mature domain is an algorithm that uses large-scale sequencing (NGS) derived sequence data to identify large insertions or deletions (INDELs) or structural variations (SVs). Establish scientific advantages and feasibility of acquiring digital genome sequences using machine learning techniques, implement result technology in a centralized clinical-grade database, and publish test results in electronic medical records (EMR) for clinical use. The SBIR Stage 1 Funds. The first case of HBOC is intended to investigate because the disease is well studied and includes many SVs that are difficult to reliably identify using current NGS technology.

Since its first submission in December 2014, the market has been explicitly referring to our framework. Illumina publicly announced a $ 100 million investment in Helix, a consumer-centric "neutral" platform that stores DNA and provides the same centralized silico acquisition in terms of functionally as YG-C. 30% of the revenue share was released. Illumina also announced LabCorp and Mayo Clinic as Helix's first app developers, using models similar to Apple's App Store. Illumina supports our plan to develop a web-enabled and cloud-based genetic testing platform to safely store and test patient DNA data for clinical use, as shown in the accompanying letter of evidence. The market also identified the value of a clinical-grade database for storing biomarkers of interest. Quest Diagnostics and INSERM recently co-founded BRCA Share ™, a data-sharing initiative that provides commercial access to BRCA1 and BRCA2 gene data on a subscription basis.

The system also includes a component for storing patient information in the system patient record database (s). A physician user or other user may enter patient clinical data, including history, attributes, physiological parameters, demographic parameters and / or laboratory test results, into the appropriate fields of the database. The system patient database (s) also include information about gene biomarkers or other biomarkers associated with a particular patient. In some cases, biomarker information of a patient, such as, for example, single nucleotide polymorphism (SNP) information, will not be known at the time of examination or diagnosis by a physician. Thus, in certain embodiments, a physician or other user may later enter the biomarker information of the patient into the system patient database (s). In view of the increase in personalized care, patients are increasingly encouraged to actively participate in the collection and management of personal health records. Thus, in the particular embodiment described herein, a patient-centered model is used to determine the use of the biomarker information of reason, so that the determination of the need to pay to the stakeholder is made by the rights holder of the particular biomarker May be triggered at the patient level rather than as a result of licensing contracts or other relationships between diagnostic laboratories or physicians.

In another embodiment, the diagnostic laboratory or physician may determine the patient biomarker and perform the tests necessary to upload the information directly to the system patient record database (s). The system then correlates the patient ' s clinical and / or biomarker information with the information in the system database (s) and / or accesses one or more public or private domain databases to generate a match for any proprietary biomarker information can do. It is also possible to compare the clinical and / or demographic information of a patient with other patient records in the patient record database (s) to identify a common SNP or other biomarker for diagnostic and therapeutic purposes, It can be determined whether or not an attribute exists. Information may then be communicated to the physician indicating that the individual shares properties with a population of individuals having a common SNP or other biomarker. Thus, the method provides genetic information that can be read for private use, and a means of using the means and information to identify the patient with the biomarker. In addition, it may be done in an automated manner to notify the insurance company or the party of the payer and to pay to the interested parties of the information of reason.

A system for implementation of the invention disclosed herein will be described with reference to FIG. In FIG. 1, a system 100 is provided having a trusted server 101 (internal dotted rectangle) for controlling access to one or more databases and for controlling payment transfers between users. Those skilled in the art will appreciate that trusted server 101 may be any configuration of one or more processors 103 (rectangles), data storage devices (rounded rectangles) and servers for performing the functions described herein will be. The system 100 may host various user interfaces (pentagrams) and functional facilities (hexagons). The trusted server 101 and in particular the one or more processors 103 are connected to the historical database 110 and the patient history database 105 in accordance with the privacy rules controlling access to the information contained in the historical database 110 and the patient history database 105, And access to information stored in the patient record database < RTI ID = 0.0 > 105. < / RTI >

The patient record database 105 includes individual patient records that include patient identification information and diagnostic information, wherein each patient record is associated with a particular individual patient. The individual patient identification information may include fields such as sex and name, birth data, physician information, address, social security or other identification number, or any other information that may potentially provide an indication of the patient ' . Those skilled in the art will appreciate that the patient record database 105 is not limited to any particular device or hardware.

The reason recording database 110 includes a record of the biomarkers of reason, information about the rights holder of the biomarker, and information about the use of the biomarker to diagnose a specific disease or condition or to indicate a risk for a particular disease or condition. Data or rules. In addition to the biomarker, the reason recording 110 database may optionally include demographic or clinical information that can be used to assess the risk to a particular disease or condition. Many biomarkers increase predictive power when used in combination with certain demographic and / or physiological parameters. For example, the presence of a particular SNP may be determined in combination with certain demographic and / or physiological parameters or information, such as age, sex, weight, height, blood pressure, EJG characteristics, or any previous history, such as a vascular stent, Can represent an increased risk for a disease or condition. Alternatively, the presence of a particular SNP may indicate a particular therapeutic regimen, such as drug administration or use of a medical device. In particular, the presence of SNPs may indicate the insertion of an implantable cardioverter defibrillator device (ICD). In some cases, rightsholder claims can only be extended with the use of one or more biomarkers in combination with specific demographic and / or physiological parameters. In such cases, the rights holder's intellectual property rights may only be relevant if there is a biomarker in the patient's record in relation to certain demographic and / or physiological parameters.

The function of the system 100 is that access to information in the patient record database 105 is limited. With regard to the information in the reason recording database 110, the intellectual property rights, particularly the scope and owner of the patent rights, are generally known. As such, access to information in the reason recording database 110 need not be limited in certain embodiments. In particular, access to patient identification information is limited to protect the patient ' s privacy. In some embodiments, access to patient identification information is granted only to the patient's physician and, optionally, to the payer party responsible for the patient, by privacy rules. Demographic and clinical information and access to biomarkers can be granted for comparison between groups as described above.

Medical information is deemed to be personal by many individuals, and disclosure of medical information, which can often be associated with a particular individual, is often considered to violate trust or violate personal privacy in accordance with social norms. In addition to the social sensitivity of medical information, doctors and other health care providers may have ethical or legal obligations to protect the privacy of patient medical information. In addition, the presence of certain biomarkers, particularly genetic information, can be used to differentiate particular patients. For example, knowledge of certain genetic information can be used by employers to discriminate in employment or to deny coverage by health insurers. The potential illegal nature of such discrimination does not preclude its occurrence.

The medical information is entered into the individual record of the patient record database 105 via the pseudo-user interface 115 or the diagnostic service provider interface 120. As shown in FIG. 1, pseudo user interface 115 communicates with trusted server 101. In a particular embodiment, pseudo-user interface 115 is located on an Internet web server where pseudo user interface 115 can be accessed using a standard HTML web browser. The pseudo user interface 115 may be a special executable program running on a processor remote from the trusted server 101 or the processor 103 and the communication with the trusted server 101 may be via the Internet or another network Lt; / RTI >

The pseudo-user interface 115 is accessible by a user with an authentication credential to identify the user to the pseudo-user 115. The physician user 115 is a medical provider or an individual overseen by a medical provider approved by the patient to enter or fill in information associated with a particular patient record in the patient record database 105. [ The physician user 115 may enter information in a patient record, including patient identification information and demographic information, manually or in an automated manner via electronic data provided by a separate electronic recording system maintained by the pseudo-user Function. Physician users can set up security rules so that physicians can access information contained in an authorized patient record, but do not have access to identifying information about unauthorized patient records.

The authority of the physician user for a particular patient record in the patient record database can be established automatically when establishing a new patient record. That is, if possessing the identified patient information used to establish the patient record, it is assumed that the physician user has authority over the patient. Alternatively, for example, if a patient transduces a healthcare provider, the authority of the physician user may be verified or authenticated by a physician user who has already accessed the system. Alternatively, a patient user interface 125 may optionally be provided so that the patient can specify the authority of a particular physician user. In certain embodiments, the patient user interface 125 does not have access to change the contents of the patient record in the patient record database 105, thus preventing a simple user from inadvertently changing the contents of the patient record.

Optionally, the trusted server 101 may also be accessed via the diagnostic service provider interface user 120. Biomarkers are physical properties that are often determined by laboratory tests that require sophisticated equipment. Thus, specialized diagnostic laboratories or diagnostic services can be used to perform diagnostic tests directly and generate diagnostic information. Diagnostic information may be communicated to the physician, and the physician may update the diagnostic information contained in the patient record via the physician user interface (115). Alternatively, the diagnostic service provider user interface 120 may be provided to allow the test laboratory or diagnostic service to directly update the diagnostic information of the patient record in the patient record database 105. [ The diagnostic service user interface may be accessible via an HTML viewer or a special executable program in a manner similar to the pseudo-user interface 115.

Since the physician generally needs access to all patient identification information and diagnostic information included in the patient record, the privacy rules operating on the trusted server 101 are stored in the patient record database 105 Lt; RTI ID = 0.0 > access < / RTI > In contrast, the diagnostic service provider typically does not need to have any significant access to patient information. As such, the privacy rules can be set such that the diagnostic service provider can upload diagnostic information to the patient history database 105 using the diagnostic service provider user interface 120. [ In certain embodiments, the diagnostic service provider does not need or need to be notified of basic patient identification information, such as name and date of birth. Rather, a unique and / or one-time reference number for a particular diagnostic test may be provided to the diagnostic service provider, and the trusted server 101 may correlate the reference number with a particular patient record to be updated.

Additional users of the system include a payor party user and a rights holder user who access the trusted server 101 via the payor party interface 130 and the rights holder interface 135, respectively. The function of the system 100 is to allow the transfer of payments from the payer party to the rights holder when the biomarker information of the incident is accessed via the pseudo-user interface 115. The process by which a physician uses system 100 to access proprietary biomarker information will be described in greater detail below.

Diagnostic tests for biomarkers and medical services, including advice based on the presence of physician care and biomarkers, are often covered by health insurance, where the patients receiving services are not responsible for 100% of the required payments. In some embodiments, the payer party user is a health insurer or other third party payer who is responsible for the particular patient represented by the patient record in the patient record database 105. In addition, the patient himself may also be responsible for all or part of the payment for accessing biomarkers of a particular cause while the physician is being treated. As such, the payer party may further include the patient in addition to or in place of the insurer.

The privacy rules operating on the trusted server 101 may be configured to only have access to the information necessary for the payor party user to approve the payment or to verify the obligation to review the validity of the payment already sent. In some embodiments, the payer party user does not need to access the nature of the diagnostic query or test actually performed, but rather needs to access only the assurance that the service performed is of the type normally approved by the particular health plan have. As such, the patient record in the patient record database 105 may include details of the identity of the payer party to that patient, along with the details of the coverage of the medical coverage provided by the payer party. The payer party user may elect to be notified that the insured patient has been assessed based on the biomarker for the reason covered by the insurance as set out in the Privacy Rules, You can request the identity of the patient, but you can choose to process the payment without knowing the exact identity of the biomarker. As such, the system 100 can ensure a high degree of patient privacy for sensitive medical information.

Generally, the payer party and the insurer access the nature of the medical diagnostic tests performed on the insured, and such medical diagnostic tests are billed to the insurer. Here, the diagnostic service provider may directly bill the payer party or the insurer directly for services performed according to customary practice. For example, a diagnostic service provider may charge a payer party or insurer for genome-wide SNP analysis or for performing blood protein analysis using a gene chip or similar test; The nature of such a diagnostic test may be communicated directly to the payer party or insurer. However, as will be described in more detail below, the system 100 allows a pseudo-user to access information about a particular biomarker measured by such a test. The payer party user or insurer may have knowledge that a genome wide SNP assay has been performed for a particular insured patient, but the physician may be required to pay for knowledge that specifically identifies the biomarker associated with heart disease, cancer or other specific disease or condition Access to the user of that party can be blocked using the system's privacy rules. Alternatively, payments to and from the diagnostic service provider user may be made through the system 100 as needed to protect the confidential patient information.

Similarly, rights holder users generally do not require access to the identity of the patient or physician who has accessed the information associated with the biomarker of a particular cause. As such, the privacy rules can be configured so that the rights holder user interface 135 can access information about the frequency of use of the biomarkers of their cause and confirm receipt of the appropriate payment. However, the name of the physician and the insurer as well as the identification information of the patient may also be blocked by the system 100 as needed.

Those skilled in the art will readily appreciate that the privacy rules described above may be varied from the above description as required by a particular user. For example, the user of the payer party may request a higher information rating to approve or review the payment for use of the biomarker for a particular reason, and the privacy rule may include identification information included in the patient history database 105 and / May be modified to change the access level for the diagnostic information. The system 100 facilitates the transfer of the anonymity of the right to use the biomarker of interest and the transfer of the anonymous payout to the rights holder of the biomarker of such reason. The present invention specifically contemplates the use of any set of privacy rules that meet the above criteria.

The system 100 includes a selective notification server 100 that is operative to send an email or other notification containing the availability of new information from the system to any user or to send notification that new information is available when accessing the appropriate interface (140). Such a notification may be made using e-mail or similar notification, or may be indicated by a prompt when the user logs in to the system 100 after the new information becomes available.

Referring to FIG. 2, access to the patient record database 105 and privileges granted to different categories of users will be discussed. The pseudo-user interface 115 includes: i) an ability to log into the system 100; ii) the ability to modify the patient record database 105 for an authorized patient record that includes patient identification information and diagnostic information; iii) the ability to submit queries to the system 100; And iv) the ability to receive results records from the query by email or by logging into the system 100. The diagnostic service provider interface 120 includes: i) an ability to log into the system; ii) the ability to update patient records in the patient record database 105 through the use of reference ID numbers and / or pseudo ID numbers with diagnostic information; iii) Ability to view previous uploads; iv) ability to review previous updates to patient records; And v) optionally, encryption or other means for hiding diagnostic information from a technician performing the transmission of data to the system 100.

Rightsholder user interface 135 includes: i) the ability to log into the system; ii) the ability to review the history of use or matching of biomarkers for reasons related to rights holder users; And iii) review the claims, payments and accounting history for the use or matching of the biomarkers of reason. The payer party user interface 130 includes: i) the ability to log into the system 100; ii) the ability to review the account balance of insured patients; iii) the ability to approve, confirm or acknowledge the need to pay rights holder users; iv) ability to review financial transaction history; And v) providing the diagnostic service provider with the ability to selectively approve the payment. The patient user interface 125 includes: i) the ability to log into the system; And ii) the ability to provide other users with access to patient-specific information.

The Phase I study evaluated current methods of detecting SV and CNVs from NGS data of cancer; Developing machine learning algorithms to bring CNV detection to clinical-grade accuracy; And will focus on validating and scaling these methods to demonstrate clinical utility. When implemented in YG-C, the algorithm of the present invention has the potential to shorten the treatment time by initiating testing using personal dielectric properties that are difficult to identify SVs. In addition, the patient's genome can be stored in the YG-C and the patient can be immediately recalled and rediscovered for new biomarkers without having to return for sequencing. The approach of the present invention eliminates manufacturing, shipping and disposal costs associated with disposable, single-purpose test kits. Finally, our integrated framework is suitable for all clinical genetic tests and is therefore used as a template for future silico tests. This development is generally applicable to all types of gene mutations as well as to those involved in cancer.

The goals and objectives of the SBIR program are consistent with the present invention's attempt to establish a framework for an innovative approach to standardizing genetic testing for cancer and other non-cancerous conditions.

Query the system

As described in connection with FIG. 1, the system 100 includes a trusted server 101 that functions to interact with a user and to implement access control rules to control access to the patient record database 105. The pseudo user interface 115 and optionally the diagnostic service interface 120 are used to populate the patient record of the patient record database 105 with diagnostic information. Diagnostic information may include large amounts of data that need to be analyzed to determine the presence of the biomarker information of interest. For example, diagnostic information may include genomic-wide genetic information that requires parsing to identify the presence of specific alleles, SNPs, or mutations.

In certain embodiments, the diagnostic information is accessed only for a specific query from a physician initiated via the pseudo-user interface 115. Thus, only the biomarker information used by the physician to assess the risk to a particular disease or condition of interest is assigned to the physician user, and there is a potential need to be paid to the rights holder by such access. For example, if genome-wide information is taken on the patient and is present in diagnostic information in the patient record, many potential SNPs or other biomarkers may potentially exist in the obtained diagnostic information. However, in most scenarios it is impractical to require payment for SNPs of all causes that may exist in an individual patient's genome determined through genome-wide diagnostic information. In addition, rights holders' intellectual property rights can only be extended during diagnostic testing, not just for detection, but for specific uses of SNPs of particular cause. In addition, intellectual property rights can only be extended to a plurality of biomarkers and / or clinical parameters present in one patient to indicate a risk for a particular disease or condition.

As such, the pseudo-user can access diagnostic information in the patient record by querying the system 100 with at least one search criterion. The search criteria may be a search for a particular biomarker and / or biomarker correlated to a particular disease or condition. A search algorithm and method for parsing through genetic information are known. Other biomarker data, such as lipidomic and proteomic data, can also be retrieved in response to a query.

The reason recording database 110 may contain, in addition to the identity of a specific biomarker, information about a particular disease or condition associated with the particular biomarker. Often, these specific diseases or conditions are specified in patents or other intellectual property grants to which the relevant rights holder is dependent. A specific disease or condition may be assigned a unique code for use within the system 100 to avoid the uncertainty of the keyword search.

As a non-limiting example, a physician may request a full or partial genomic evaluation of a patient, wherein the generated diagnostic information is loaded into the patient record of the patient record database 105. The physician may then submit a query to the system 100 via the physician user interface 115 to retrieve SNPs associated with a risk for heart disease. In certain embodiments, trusted server 101 or other processor may iteratively search for genetic information included in diagnostic information for proprietary biomarker SNPs and / or other SNPs associated with cardiac disease. Known search engines and parser algorithms such as BLAST, BioJava (http://www.biojava.org/wiki/Main Page) or BioParser (http://bioinformatics.tgen.org/brunit software / bioparser /) Can be used to retrieve diagnostic information about the relevant biomarkers. The sub-database table or result record may be populated into the relevant patient record of the patient record database 105 with information extracted using a parser algorithm, which parses the original diagnostic data only once to extract the biomarkers associated with the query It will eliminate the need.

Identifying the biomarker of interest in response to a physician query may thereby enable the use of one or more rightsholders' intellectual property rights and then initiate a process of transferring, describing, or escrowing the payment to the rights holder. The trusted server 101 updates the payment log or database 150 to determine a monetary amount for the use of the biomarker of interest at the time of a successful query by a physician user returning the biomarker of interest in response to the query Deposit to the appropriate rights holder. There may be a payment agency 160 to process payment to the rights holder user from the payer party user. The payment may be automatic or may only be made after approval by the payer party user using the payer party user interface 130. [ In certain embodiments, the system 100 does not complete the actual fund transfer between bank accounts. Rather, the payment is completed for the purposes of the present invention and the appended claims when the payment log or the balance of the database 150 is updated to reflect the obligation of the payer party user to transfer the funds. The funds may be periodically remitted to the administrator of the system 100 by the payer party or to the other party as an escrow where the manager can remit funds to the appropriate rights holder and pay the amount specified in the log or database 150 Remittance takes place. In another embodiment, the payment institution 160 may be programmed with the banking information of the associated user and may be stored in a computer-readable storage medium, such as an automated clearing house (ACH) or other electronic means, Payments may be initiated periodically between the payer party user and the rights holder user in a manner that ensures anonymity. The funds may be transferred first through a bank account setup for system administration to protect the identity of the payer party, which may expose patient identification information.

If more than one Rightsholder User owns the right to biomarker information for the reason for which they were returned from the query in the results record, the payment of the user of the payer party using the agreed calculation shall be made between the rights holders of the proprietary biomarker information And can be automatically divided by using the system 100. For example, a first rights holder may have a patent claim for a first SNP biomarker that is indicative of a cardiac disease risk, and a second rights holder user may have a patent claim for a second SNP biomarker that represents a cardiac disease risk You can own a range. The system 100 and the payment institution 160 can automatically and simultaneously notify the first and second rights holder users of the biomarkers found in one patient and then the pre- Can be done to allocate. In this manner, the individual patient costs can be distributed across all patients using the system 100, so that using the system and method of the present invention, the rights holder user will not be aware of particular patient identification information (e.g., blinded).

An additional feature of system 100 is that the use of proprietary biomarkers may be due to a particular patient. That is, the patient record may be annotated, for example, to indicate that the use of a particular biomarker has been accessed and paid in the past by the result recording. In certain embodiments, the patient may go to another physician to obtain a second opinion and / or the same or different diagnostic tests associated with biomarkers already paid in the past may be performed. Patients may be granted a limited license that allows for future use of biomarkers for reasons of past access. Thus, the patient can receive a second opinion and / or additional diagnostic test without additional payment.

For example, patient records may be updated to reflect past biomarkers and previously paid amounts of reason for access. When a future query is made that generates a result record that includes a previously accessed biomarker, the system may be configured to allow further use of the biomarker for the reason without additional payment. In certain embodiments, the length of time that future use of biomarkers of previously accessed reason can be made can be limited to the set time. The patient record may be annotated to indicate the date that the biomarker was first accessed to allow the calculation of expiration of the license for future use, where the amount of time of the right to use the biomarker is recorded in the historical database 110 Can be displayed.

The system may also correlate patient demographic and physiological information with information accessed from one or more public or private domain databases, such as within the system and / or a SNP consortium, and may be genetic, proteomic, and / Lt; RTI ID = 0.0 > test < / RTI > In a further embodiment, the invention also relates to displaying an identified correlation to help determine the statistical significance of the identified correlation. It is also possible that the patient's diagnostic, clinical and physiological information is compared to other patient records in the database to provide a common attribute to the population identified by the system of the present invention as sharing a common biomarker for use in diagnosis and treatment It can be determined whether or not it exists. The information can then be communicated to the physician to indicate that the individual shares properties with a population of individuals having a common biomarker. Such information may be included in the record as a result of generating a physician query.

Referring to FIG. 3, an exemplary process for querying system 100 for a biomarker of interest and remitting payment to a rights holder user in an unknown manner will be described. At step 310, the physician requests that the original diagnostic data generated by the diagnostic test perform a specific diagnostic test that may include the biomarker of interest. At step 320, the original diagnostic data is uploaded to the system 100 for addition to a particular patient record in the patient record database 105. The original diagnostic data can be uploaded by the diagnostic service provider, and the patient record is identified by a reference number that maintains the anonymity of the patient. In another embodiment, step 320 may occur prior to step 310, and previously uploaded data may be invoked from system 100.

At step 330, the physician queries the system to find a particular biomarker in the original diagnostic data and / or to find or predict a risk for a particular disease or condition. The patient ' s records database is accessed by the system 100 and the original diagnostic data is parsed to identify the biomarkers of interest having characteristics consistent with the query. At step 340, a result record is generated that includes the biomarker returned by the query, and optionally a notification of the payor party user who is responsible for the physician and / or patient, or the rights holder user associated with the biomarker of the proprietary biomarker do. The patient record may be updated by the contents of the result record or query. At step 350, the payment log or database is updated to reflect the need for payment between the payer party user and the rights holder user in an unknown manner.

Database structure

Figure 4 illustrates a non-limiting example of a database structure that may be used in connection with the methods and systems described herein. One of ordinary skill in the art will readily recognize that other database structures and organizations may be equally used to implement the methods and systems described herein. Figure 4 shows the structure of a relational database that can be accessed using a structured query language (SQL) and can retrieve the obtained query.

Figure 4 shows a relational database with multiple tables having rows and columns associated with the categories described in the header. As shown in tables 410-445 of FIG. 4, exemplary attributes for each table are listed. The first attribute of each table 410-445 may be used as a key to associate information in the table with other related tables using SQL. More specifically, the first attribute of each table may serve as a candidate key that is not duplicated in any one table. The organization of Tables 410-445 will now be described.

Table 410 includes patient identification information. The attributes may include a patient identification number, a patient's name, contact information, a doctor's name and / or a physician user identification number, and an insurance company information and / or a payment user identification number. Those skilled in the art will readily recognize that other attributes may be included in the patient identification table 410. [ As described, the protection of the information contained in the patient identification table 410 is tightly controlled to protect the patient ' s privacy. As such, sensitive information about the patient's identity can be separated in the table 410 to prevent unauthorized disclosure of such information.

Data and information associated with a particular patient that may have less stringent control for access may be stored in a table separate from the table 410. As shown in FIG. 4, a diagnostic data table 415 may be provided. In addition to including a patient identification number attribute, the table 415 may include additional attributes associated with various diagnostic tests performed on the patient associated with the patient identification number. Examples of attributes that may be provided on the diagnostic data table 415 include the presence or absence of specific SNPs, WGS, WES, or target genetic information, proteomic and / or lipidomic information, Results. Similarly, table 420 may include information about the medical history of a particular patient. In addition to including a patient identification number attribute, table 420 may include additional attributes such as previous diagnosis, current prescription, height, weight, age, and other attributes typically included in the medical record. Specific attributes of tables 415 and 420 may be indicated by reference numerals rather than word strings to facilitate querying of the system.

Tables 415 and 420 may be restricted through use of the foreign key shown as FK1 in Fig. The foreign key FK1 may be used to ensure that a patient identification number attribute on the tables 415, 420 occurs and has a valid entry in the patient identification table 410. [ The foreign key FK1 may also be used as a constraint condition to ensure that the patient identification numbers contained in the other table occur in a table that shares the relationship, as shown in FIG. For example, foreign (FK1) may restrict the system or any user from entering information into the diagnostic data table 415 with a patient identification number that does not appear as an attribute in the patient identification table 410.

As described, the systems described herein provide various user interfaces for interacting with the system, including entering information into the system and submitting queries. The user table 425 may have attributes including a user identification number, a user name, a user type, and a login credential. The user type (e.g., pseudo-user, rights holder user, etc.) can be used by the system to present a suitable user interface to the user logging on to the system. The user table 425 includes what privilege a given user of a patient identification number has and includes a privilege table 430 defining access rights within the privacy rules that operate on the system in connection with access to the patient identification table 410 ). ≪ / RTI > The foreign key F2 may be implemented to restrict the privilege table 430 to include only the user identification number attribute that appears in the user table 425. [

The biomarker table 435 may also be associated with a user table 420. The biomarker table 435 includes a combination of biomarkers and other information indicative of intellectual property owned by a particular rights owner user. In general, the user identification number attribute on the table 435 is associated with the rights holder user. The diagnostic reference number may be provided as an attribute indicative of an individual diagnostic test indicating the intellectual property rights of the rights holder user.

For example, certain combinations of biomarkers may indicate increased risk for cancer. By way of example, a rights holder may be the owner of a claim claiming that the presence of a G nucleotide of SNP1, and a C nucleotide of SNP2, and a body weight in excess of 200 pounds of man represents an increased risk of certain types of cancer , And SNP1 and SNP2 represent specific genomic loci in the genome. Biomarkers SNP1 and SNP2 and clinical parameters relating to weight and sex may be organized in the same row of the biomarker table 435 associated with a unique diagnostic reference number attribute. Figure 4 illustrates a non-limiting example of a biomarker that includes SNPs, WGS, proteomic and / or lipidomic information, physiological parameters and demographic parameters that may be associated with specific intellectual property rights. The rows of the table 435 may also include charge information associated with the use of diagnostic tests indicated by the corresponding rows of the table 435.

As described above, the system may be queried to identify patients with a particular biomarker or combination of biomarkers and / or clinical parameters that are indicative of an increased or reduced risk for a particular disease and condition. The search engine associated with the system may retrieve a match between the specific intellectual property rights stored in the history table 420 and the biomarker table 435 having the information stored in the diagnostic data table 415. [ As described, the system may be queried, for example, to determine if a particular patient has any biomarkers and / or clinical parameters associated with an increased risk for cancer. The system then determines the presence or absence of any combination of biomarkers and / or clinical parameters associated with the annotated diagnostic reference number to correlate the risk to cancer with the information stored in the diagnostic data table 415 and / We will systematically search for occurrences.

Any matching from the query may be recorded in the result recording table 440 as shown in FIG. The result recording table 440 may list the patient identification number for the patient with at least one match to the diagnostic reference number. The foreign key FK3 may be used to limit the result recording table 440 to include only the diagnostic reference number that appears in the biomarker table 435. [ The payment log table 445 may be provided to record the activities of the payment institution 160. The payment log table 445 may include a patient identification number and a diagnostic reference number indicating a match from the query as in the result record table 440. [ The foreign key FK4 may be provided to limit the payment log table 445 to include only the entry for the combination of the patient identification number attribute and the diagnostic reference number attribute occurring in the result recording table 440. [ Payment log 445 may include additional information regarding the status of the notification for the user regarding payment and any pending payment status between any users of the system.

hardware

Figure 1 illustrates the functionality of the systems and methods disclosed herein. The above-described functions may be implemented on any hardware system suitable for executing the functions described above. However, a non-limiting example of a hardware system for implementing the present invention is shown in Figs. 5 and 6. Fig.

FIG. 5 shows a hardware implementation that may be deployed on a single server 501, where a single server may be a laptop or desktop computer. The server 501 functions as the trusted server 101 described in Fig. The user 505 of the server 501 can communicate with the server 501. [ The communication may be via the Internet or other network means; An Internet connection is not required to practice the present invention. In a particular embodiment, the user 505 may communicate with the server 501 using a widely available HTML viewer.

The user 505 first communicates with the security module 510 implemented on the server 501. [ The security module 510 may be a form-based authentication in which the user is verified using a username and password combination. The username and password combination will identify the physician 510 as a physician user, a diagnostic test provider, a patient user, a payer party user or a rights holder user and implement the appropriate interface and associated privacy rules to control access to information. Alternatively, access to the server 501 may be granted based on the user uploading the secure file containing the encrypted identification information.

The server 501 implements a web server that includes a user interface (UI) 525 presented to the user 505. UI 525 is not limited to any particular software, standard, or language. In a particular embodiment, the UI 525 may be based on a JavaScript library that includes a robust JavaScript Library Toolkit that supports the HTML5, CSS3.0, and Web 2.0 standards. The UI 525 may thus be a graphical interface that can be intuitively manipulated by the user 505. As described above, one or more parser algorithm tools or search engines 530 may be implemented on the server 501 for parsing gene data. In one embodiment, the parser algorithm tool 530 can be BioJava (http://www.biojava.org/wiki/Main Page), which has the advantage that it can be easily implemented as a JAVA based web server. In another embodiment, the parser algorithm tool 530 may be a BioParser (http://bioinformatics.tgen.org/brunit/software/bioparser). Because BioParser is written in PERL, a wrapper is required to implement a BioParser with a JAVA-based web server, for example JPL or JNI. 1, the notification server 140 sends a notification to the included JAVA mail client 535 to send a notification to the user 505, even if the user 505 is not logged on to the server 501 Can be implemented. The mail client 535 may also implement a payment institution 160 that may be notified of the obligation to perform the payment in a manner unknown to the payer party user and / or rights holder.

The patient record database 105, the reason recording database 110, and the payment log or database 150 may be received on the storage device 540. The database stored on storage device 540 is not limited to any particular structure. In some embodiments, the patient record database 105, the reason recording database 110, and the payment log or database 150 may be evaluated using a structured query language (SQL) used to maintain the relational database and / Queryable. In one embodiment, the database uses a relational database management system, such as Oracle 8i ^TM product (version 8.1.7), by Oracle. In another embodiment of the database, an object-oriented database management system architecture is used.

Figure 6 illustrates a hardware implementation that uses multiple processors for large-scale implementations. The functionality of the one or more processors 103 described in FIG. 1 provides the computing power to implement the UI, the parser algorithm and the security module 610 in the same manner as described in FIG. 5, Is performed by one or more processing units (603). A load balancer 612 is also present for managing the workflow in an implementation in which there is more than one processing unit 601. [ The load balancer 612 divides the work load multiprocessing unit 601. If a fault occurs in one of the processing units 601, the load balancer 612 may automatically route the request from the user 605 until the fault is corrected.

The processing unit 601 may access a storage area network (SAN) that contains a patient record database 105, a reason recording database 110, and a payment log or database 150. A separate mail server 635, which includes dedicated processor capabilities, may be present to generate a large amount of outgoing email. The payment institution 160 may be implemented using one or more processing units 603.

An overview of the system for providing biomarker test results is shown in FIG. The control server 751 may be connected to the remote client 752 (760). In some embodiments, control server 751 may be on a server, virtual instance, intranet, or cloud separate from remote client 752. In another embodiment, the control server 751 may be located in the same server, intranet, or cloud as the remote client 752. To avoid having to send large data genetic files to be transferred over the Internet and / or across firewalls, a remote client 752 may be co-located on the same server, intranet, or cloud 758 as the genetic data store server 753 It is important that it can be located. The gene data storage server 753 includes genetic or other biological data of the patient. The control server 751 may also be coupled to the gene data interpretation server 755 (761). The gene data analysis server 755 includes a biomarker script that enables interpretation of genetic or other biological data stored on the genetic information storage server 753. In some embodiments, the listener 754 may optionally be used to create a dedicated server process with the gene data interpretation server 755. [ The listener 754 and the genetic data interpretation server 755 may optionally be co-located on the same server, intranet or cloud as the control server 751 or they may be located separately from the control server 751 in a separate server, Lt; / RTI >

A request for a genetic test or other biological test may be made 762 by the healthcare provider or other user 756 to the control server 751. In some embodiments, the request may be made through the patient's electronic health record or electronic medical record. In some embodiments, the request may be made directly to the remote client 752 via the third party request application 757. [ The request may be sent to control server 751. The control server can obtain the necessary biomarker script from the gene data analysis server 755 and transmit the biomarker script to the remote client 752. [ The remote client can execute the biomarker script on the data stored in the gene data storage server 753. [ The results of the biomarker script may be sent back to the control server 751 and the control server may send the results 763 to the user 756. [

The query system of the present invention according to one embodiment is illustrated in FIG. A user of the system, such as the hospital 703, the laboratory 704, the government agency 705, or any other authorized user, may access the YouGene portal 700 located on the opposite side of the firewall 706. In some embodiments, a request for a test may come directly from the patient's electronic health record or electronic medical record. In another embodiment, the request for testing may come through health information exchange. A user may access the portal via the Internet 702, for example, using a web browser such as Firefox, Internet Explorer or any other web browser. Communication between the user and the portal can be established using SSL, HTTP, HTTPS, SOAP, or any other method known to those skilled in the art. The user may be authenticated and authorized through the service authentication manager 715, LDAP 716, or any other authentication mechanism. The signal may be transmitted via load balancer 707 and switch 708 to reach portal 700. [ When the user logs in, the user will access the information based on the user type according to the business rule set 709. The ability to access the information may be controlled via the content manager 710.

A query of the gene or other information may be sent to the database 714 via the application server 711. In some embodiments, database 714 may be owned and operated by a private company. In another embodiment, the database 714 may be owned and operated by a third party. The search engine 712 may query the database upon request. The notification engine 713 may compile the results from the query. The result may be transmitted to the user via the file transfer system 701. The security and effectiveness of the entire system can be monitored by the monitoring system 717 and the management console 718. [ Communication between the servers may be established by any means known in the art, including TCP / IP. Communication with the database may be established through any means known in the art, including JDBC.

The system described herein has efficiency based on data enforcement, consistent / integrated UI, standardized security such as authentication and authorization, and security enforcement of roles based on access control. In some embodiments, standardized business event notifications may also be provided when new or updated or related information becomes available.

The modules and functions of the system are shown in FIG. The control server (CS) 816 may be hosted on the Web, in the cloud, on the server, or in any other location. CS 816 may exchange information between one or more databases located on the same or different servers.

In one embodiment, the remote client application (RCA) 815 owned by the first company may also be a web, cloud, intranet or server hosted application. The RCA 815 may associate with the CS 816. There can be multiple RCAs in the same RCA or in a separate cloud, intranet, or server. In some embodiments, RCA 815 may be a temporary application on a remote cloud, intranet, or server. In another embodiment, RCA 815 may be permanent.

Gene Data Storage Server (GDSS) 810 may be a web, cloud, intranet or server data repository that is owned and operated by a second company behind a firewall. In some embodiments, the GDSS 810 may be operated and maintained by the first company. In another embodiment, the GDSS 810 may be operated by a third party, e.g., a second company. The GDSS 810 may include one or more digital test records. In some embodiments, the digital test record may comprise a genetic test record. In another embodiment, the digital test record may include other biological test data such as protein or enzyme information. The GDSS 810 may communicate with the RCA 815 located together and may respond to requests from the RCA 815 and provide test results. Significantly, the GDSS 810 is on the same server, virtual instance, intranet, behind the same firewall as the RCA 815, or in the same cloud environment 821. This eliminates the need to transmit sensitive and large-volume digital test results over the Internet. In some embodiments, RCA 815 may be embedded as part of GDSS 810. [ In another embodiment, the RCA 815 may operate outside the GDSS 810, as long as the RCA 815 is located with the GDSS 810. [

An example of a Gene Data Storage Server (GDSS) is the Illumina® sequencing and array-based solution system, for example, BaseSpace. Other currently known gene data storage servers may include Curoverse, GA Biobank, or any other known biological repository. The GDSS system generally provides sequencing and storage of gene data. However, any storage system, biobank, data repository, bioregistration or data exchange site capable of storing genetic data in WGS, WES or any other known and appropriate output is contemplated by the present invention. In some embodiments, the gene data storage server may be any HIPAA compatible server capable of storing genetic data.

The Gene Data Analysis Server (GDIS) 817 may be a web, cloud, virtual instance, intranet, or server-based data repository. The GDIS 817 may be operated by a first company or a third party. The GDIS 817 may include one or more biomarker scripts, and a clinical interpretation is made based on the results generated for the biomarker script.

The digital patient information storage server (PISS) 818 may be a web, cloud, intranet or server hosted data store. In some embodiments, the PISS 818 may be operated by a first company. In another embodiment, the PISS 818 may be operated by a third party. The PISS 818 may include one or more patient records. The PISS 818 can communicate with the CS 816 and can be operated to update, edit or delete patient information.

One or more listeners can be used in any data store to create a dedicated server process for each user, thereby improving efficiency and reducing memory limitations. In some embodiments, the data may be communicated using JSON or other communication protocol.

CS 816 may be hosted in a separate cloud environment, intranet, or server 822, separate from RCA 815. However, in some embodiments, the CS 816 may reside in the same cloud environment, intranet, or server as the RCA 815. In some embodiments, CS 816 and RCA 815 may be located in a single intranet. GDIS 817 and PISS 818 are shown in Figure 9 as being in a single cloud, intranet, or server 823. In another embodiment, GDIS 817 and PISS 818 may reside in separate clouds or servers. In some embodiments, GDIS 817 and PISS 818 may be in the same cloud, server, or intranet as CS 816.

After all the software is installed, a communication portal 801 can be established between the CS 816 and the RCA 815. A second communication portal 802 may be established between the CS 816 and the PISS 818. A third communication portal 803 may be established between the CS 816 and the GDIS 817. A fourth communication portal 814 may be established between the RCA 815 and the GDSS 810. [ The communications portals 801, 802, 803, and 814 are suitable for transmitting secure and non-secure information between TCP, UDP, VPN, socket, OS messaging, or between two instances of software located or not co- And may be established and maintained through any combination of equivalent techniques.

In certain embodiments, a library, DLL, extension, or API may be an operator, such as Illumina Basespace, or an API that can be integrated into the GDSS owner software that allows the GDSS owner to integrate external code to perform scans within that module Can be recorded in a gene data storage server (GDSS) such as any local hosting server. In this manner, the GDSS may remain isolated and protected, but receives commands via the remote client described herein. In particular, the embedded software, DLL or API acts as a remote client and communicates with the control server, but can be embedded in other applications.

For example, a recipe for testing the biomarker 804 may be obtained from the patient's electronic health record or electronic medical record, or from the health care provider 820, by the CS 816. In some embodiments, the health service provider may generate the prescription directly through the electronic health record and send the prescription directly to the CS 816. Non-limiting examples of services that directly generate prescriptions through electronic medical records include Allscripts® or Surescripts®. However, any electronic prescription service is also contemplated by the present invention. In another embodiment, the prescription 804 may be transmitted by the health service provider to the CS 816 via a user interface (not shown).

In certain embodiments, an environment may be provided for running open source and / or commercial tools (e.g., Galaxy, GATK, etc.). The environment can provide deep provenance and reproducibility over all connections and provide a means to flexibly configure data and ensure data integrity. In certain embodiments, the present invention contemplates a means for performing distributed batch processing operations that provides secure sharing of data sets. The present invention also contemplates providing a common set of APIs that enable application and pipeline portability across systems. The present invention can be platform and system agnostic. In each example, the present invention is capable of handling storage and organization of large data sets (e.g., BAM, FASTQ, VCF, etc.) and storing metadata about files for a very wide variety of organizational schemas can do. The present invention also eliminates the need for stakeholders such as gene data stores, prescriber or control application owners to receive access to virtual machines (VMs) on an individual or public cloud, thereby eliminating the need to manage separate physical servers Environment. In any embodiment, any service described herein, including prescriptions, connections and scripts, may be accessed via APIs.

For example, prescription 804 may be communicated to CS 816. Digital test identification information 805 may be retrieved from PISS 818 and communicated to CS 816. The digital test identification information may include the information necessary to locate one or more digital test records from the GDSS 810. [ The digital test identification information may be transmitted 806 to the RCA 815 for the purpose of locating one or more digital test records from the GDSS 810. The digital test record may be retrieved and sent back to the RCA 815 (807). The digital biomarker script may be retrieved 808 from the GDIS 817 and sent to the CS 816. The CS 816 may send the digital biomarker script 809 to the RCA 815. The script may be responsible for providing the RCA 815 with instructions necessary for the interpretation of genetic or other biological data according to the biomarker test prescription 804.

In certain embodiments, the biomarker test prescription 804 may include any one or more of a biomarker identifier, a patient identifier, a pseudonym identifier, a payer identifier, a test data identifier, and a test data location identifier, Multiple GDSSs and RCAs are used as described herein.

The RCA 815 may execute the instructions of the biomarker script operating on the digital test record. The result of the script may be returned to the CS 816 (811). The results of the script may be communicated to the prescriber 819 (812). In some embodiments, the results may be communicated electronically (812). In another embodiment, the results may be communicated to the prescriber 819 via all possible means of communication (812). The results of the script may also be stored in the PISS 818 (813).

In this way, the genetic information of a patient can be queried, analyzed, and transmitted without having to transmit the patient's actual genome through the Internet. In another embodiment, the PISS 818 is unnecessary. Certain patient information may be obtained directly from the prescriber 820 and transmitted to the CS 816.

10, a request for a test result is sent from the same server, virtual instance, intranet, or cloud 923 as the RCA 918 to the third party request application 922 via the third party request application 922. In an alternative embodiment, This can be done directly by the requestor of the parties. The third party requestor may connect directly to the RCA 918. This embodiment may allow requests and test results to be executed and returned without having to send information over the Internet. In an optional embodiment, third party request application 922 and RCA 918 may be co-located. A communication portal 915 may be established between the third party request application 922 and the RCA 918. Communication portal 914 may be established between RCA 918 and GDSS 910 and communication portal 901 may be established between RCA 918 and CS 919 and communication portal 903 may be established between RCA 918 and CS 919, CS 919 and GDIS 920 and communication portal 902 may optionally be established between CS 919 and PISS 921. [ In operation, the system operates similarly to the system of FIG. A request for test results 904 is sent from the third party requesting application 922 to the RCA 918. In some embodiments, a third party requesting application may be embedded in the GDSS 910 as described herein. RCA 918 communicates a request for patient information 916 to CS 919. The digital test identification information 905 corresponding to the request may be retrieved from the PISS 921 and communicated to the CS 919. The digital test identification information may be sent 906 to the RCA 918 for the purpose of locating one or more digital test records from the GDSS 910. The digital test record may be retrieved and sent back to the RCA 918 (907). Requests for the digital biomarker script 917 may be sent from the RCA 918 to the CS 919. The digital biomarker script may be retrieved from GDIS 920 (908) and sent to CS 919. The CS 919 may send the digital biomarker script 909 to the RCA 918. The script may be responsible for providing commands to the RCA 918.

The RCA 918 may execute instructions in the biomarker script, which operate on the digital test record. The result of the script may be returned 911 to the CS 919 and the result may be sent 912 to the third party requesting application 922. In some embodiments, the results of the script may also be archived in the PISS 921 (913).

Significantly, the RCA 918 may be located in the same server, virtual instance, intranet, or the same cloud 923 as the GDSS 910. The CS 919 may be located in a separate server, virtual instance, intranet, or cloud 924 from the RCA 918. GDIS 920 and PISS 921 are shown on a single server, intranet, or cloud 925. In some embodiments, GDIS 920 and PISS 921 may reside on separate servers, intranets, or the cloud. In another embodiment, one or both of GDIS 920 and PISS 921 may be located on the same cloud, virtual instance, intranet, or server 924 as CS 919.

This system is not limited to one prescription source or one digital test database. A plurality of databases and request sources can be accommodated as shown in FIG. The CS 1001 includes a first RCA 1002 located with the first GDSS 1003, a second RCA 1004 located with the second GDSS 1005, a second RCA 1004 located with the third GDSS 1007, 3 RCA 1006, a fourth RCA 1008 co-located with a fourth GDSS 1009 and a fifth RCA 1010 co-located with a fifth GDSS 1011. Any number of RCAs, each corresponding to an individual GDSS, are contemplated by the present invention.

Similarly, the CS 1001 may receive prescriptions from multiple sources. The first provider or requester 1012 may provide an electronic medical record or electronic health record 1014 that can communicate the biomarker test prescription 1016 via the subject-host machine interface 1013 or through the interface application 1015. [ A biomarker test prescription 1016 may be provided. The second provider or requestor 1017 may provide an electronic medical record or electronic health record 1019 that can communicate the biomarker test prescription 1021 via the subject-host machine interface 1018 or via the interface application 1020. [ A biomarker test prescription 1021 may be provided. The third provider or requester 1022 may provide an electronic medical record or electronic health record 1024 that may communicate the biomarker test prescription 1026 via the subject-host machine interface 1023 or via the interface application 1025. [ A biomarker test prescription 1026 may be provided. Again, any number of providers or requestors are contemplated by the present invention. In an embodiment, as shown in FIG. 11, the biomarker test prescription may include a test data location identifier that can point to a particular RCA and GDSS so that the CS can communicate.

In an embodiment where the third party request is initiated from the same server, intranet or cloud as the RCA, as shown in Figure 12, the system is not limited to a single GDSS and RCA. The CS 1101 includes a first RCA 1117 located with the first GDSS 1118, a second RCA 1119 located with the second GDSS 1120, Lt; RTI ID = 0.0 > RCA 1121 < / RTI > Any number of RCAs located together with the GDSS are contemplated by the present invention. The first provider or requester 1102 may initiate testing via an electronic health record or electronic medical record 1104 that may act as a third party request application 1103 or through the interface application 1105. [ The biomarker test recipe 1106 may communicate directly with the first RCA 1117. The RCA 1117 may communicate with the CS 1101 and the GDSS 1118 as described above to perform the test and notification procedures. The second provider or requester 1107 may initiate the test through the electronic health record or electronic medical record 1109 that may act as the third party request application 1108 or through the interface application 1110. [ The biomarker test recipe 1111 may be communicated directly to a second RCA 1119 that can communicate with the GDSS 1120 and the CS 1101 that are co-located to perform the biomarker test. The third provider or requester 1112 may initiate the test through the electronic health record or electronic medical record 1114 that may act through the third party request application 1113 or through the interface application 1115. [ The biomarker test recipe 1116 may communicate directly with the third RCA 1121, which may communicate with the GDSS 1122 and the CS 1101 that are co-located to perform the biomarker test.

It is understood that any number of providers or requesters may initiate testing via a single RCA. It will also be appreciated that any number of RCAs located together with the GDSS may be considered by the present invention.

In certain embodiments, the gene scanning function described herein can be combined with the biomarker function of the subject matter. One embodiment of an implementation of the combined system is shown in FIG. The third party requestor may initiate and perform genetic testing, and the control server of the present invention may act to facilitate the transfer of the biomarker rights of interest. The third party requestor 1205 may initiate a genetic test from the GDSS 1206. [ The third party scanning application 1205 may transmit the gene utilization data 1212 to the remote application 1204 to ensure that the license for the proprietary biomarker or test information is properly obtained. The gene utilization data may include information about the test to be performed and the biomarker to be searched. Remote application 1204 may send this gene utilization data 1215 to control server 1201. The control server 1201 may include information on proprietary biomarkers or ownership of test information and license agreements. The control server 1201 may transmit the gene utilization information to the biomarker or the test owner 1202 for the reason. As described herein, for a given genetic test, more than one rights holder may be involved. As such, the control server 1201 may transmit the gene utilization information to any and all rights holders 1202. It is shown in FIG. 13 as three different parties, but it will be understood that any number of parties may have rights associated with any test. Rights holder 1202 may transfer license 1216 to the owner of control server 1201. The control server 1201 may retransmit the gene utilization information 1219 to the third party 1203 for payment. 13, the third party scan application 1205 is owned by a third party that is not the owner of the control system. The license obtained by the rights holder may also be transferred 1218 to the third party 1203 as discussed herein. The third party 1203 may make a payment of the license fee 1208 to the owner of the control server 1201. Control server 1201 may also communicate royalty payment 1217 to rights holder 1202. [ As described herein, the scanning application may be located with the GDSS 1206 on the cloud or server 1207. To protect privacy, the GDSS 1206 and co-located applications may be protected behind a firewall 1220. The modules described in Figure 13 permit the accounting and transfer of rights of reason necessary for genetic testing by the central control system and payment for such rights.

It will be appreciated that the timing or sequence of steps described in FIG. 13 may vary. For example, if the test result is not positive, it may not be necessary to obtain a license for the reasoning test. As such, royalty payments 1217, licensing fees 1208, and license transactions 1216 and 1218 may occur after all genetic information scanning. In another embodiment, the transfer of results 1219 may be delayed 1208 until after the license fee is paid.

In some embodiments, control server 1201 may act as a licensing warehouse as described herein. Control server 1201 may obtain a license for genetic testing of the reason from various genetic IP owners 1202. [ The control server 1201 can then transfer these licenses to the third party test requester 1203 as needed. The license may be obtained independently of the genetic test request, or may be obtained whenever a test of a particular cause is requested. In some embodiments, the control server 1201 may periodically or continuously search databases, indexes, catalogs in various languages for patented or proprietary gene biomarkers and related information as discussed herein. You may obtain a license for the use of this biomarker or test, whether or not there has been a request.

Another embodiment is shown in Fig. Requests for genetic testing may be initiated by the control system 1301. [ Such a request includes a request from an electronic health record or an electronic medical record and may come from an external source 1307. [ Requestor 1307 may send a genetic test request 1317 to control server 1301. The control server 1301 may send the request to the remote application 1304. In some embodiments, the test may be executed by the third party scan application 1305. [ In such an embodiment, the remote application 1304 may send the genetic request 1309 to the third party scan application 1305. [ The third party scan application 1305 may make a request 1310 to the GDSS 1306 for the genetic information of a particular patient. The GDSS may send the gene data 1311 back to the third party scan application 1305 where the scan can be performed. The results of the scan may be sent 1312 back to the remote application 1304 as well as the gene usage data 1313 needed to coordinate the licensing agreement. The remote application 1304 can send the gene utilization information 1314 as well as the result of the test 1315 back to the control server 1301. [ The result of the test may be sent to the original requester 1307 (1316). Similar to the embodiment shown in FIG. 13, the control server 1301 of FIG. 14 may determine the rights holder 1302 of the biomarker or test for the incident and the information about the test 1323 to the rights holder 1302, Lt; / RTI > The license is obtained 1322 from the rights holder and transferred 1321 with the third party 1303 that performed the genetic test, along with the gene usage information 1320 about the performed test. 14, the third party scan application 1305 is owned by a third party that is not the owner of the control system. The requestor or a separate payer party may make a payment to the control server 1301 (1318). This payment may include a test fee 1319 that may be transferred to the third party 1303 that performed the test. The payment from the requestor may also include a licensing fee that can be paid by the control server 1301 as royalties 1324 to the rights holder 1302. [ As discussed herein, to protect privacy, the scanning application 1305 may be co-located on the cloud or server 1325 with a GDSS 1306 behind a firewall or other security 1326. [ In some embodiments, both payment, licensing, and other functions of the system may occur on the opposite side of the firewall 1326.

As discussed herein, the sequence of events illustrated in FIG. 14 may vary. For example, payment of licensing fees and royalties may occur prior to genetic testing. In some embodiments, the control server may obtain a license for a genetic test or biomarker for a reason before any request involving information of reason is made. In some embodiments, the payment from the requestor may be made by a separate transaction, such as a payment primarily covering the license fee, and a payment for the second genetic test. It will be appreciated that some of the depicted steps may be omitted. For example, a genetic test fee may be negotiated and described directly between the requester and the third party without using the control server.

As discussed herein, gene scanning need not be performed by a third party. As shown in Figure 15, the remote application 1404 communicating with the control server 1401 can directly perform genetic testing without a third party scanning application. Requestor 1406 may send a genetic test request 1407 to control server 1401. The control server may be located with the GDSS 1405 on the cloud or server 1419 behind the firewall 1420. The control server may send the request 1408 to the remote application 1404. The remote application may request the GDSS 1405 for the patient's gene data 1409. [ The GDSS may send the genetic information 1410 back to the remote application 1404 for scanning. After scanning the data, the test results may be sent to the control server 1401 (1411). The gene utilization information 1412 can also be sent to the control server 1401. The control server 1401 may transmit the gene utilization data 1413 to the proprietary biomarker used or the rights holder 1402 of the test. A license for using the information of reason may be obtained 1414. The results of the genetic test may be sent to requester 1406 (1415). The requestor or payor party 1406 may make payment 1421 via the control server 1401. This payment may include payment for usage of the gene data storage server 1416 which may be transferred to the rights holder 1402 (1416) and which may be transferred to the owner of the GDSS 1403 (1417). In the system described in FIG. 15, it is understood that the GDSS 1403 is owned by a third party other than the owner of the control server. If necessary, gene utilization information may be sent 1418 to the owner of the GDSS 1403 to account for the cost.

In some embodiments, the system may be configured to determine a new biomarker for a genetic disease. Since multiple genetic tests can be performed multiple times, the system can automatically determine if a new biomarker is present. For example, the system may be configured to automatically begin to search for new biomarkers for a particular disease associated with a known biomarker whenever the number of tests for a known biomarker exceeds a predetermined number. In some embodiments, the predetermined number may be 500. In another embodiment, a predetermined number of tests for a given biomarker may be any of 200-500, 400-600, 500-1000, or more, before the system can automatically retrieve the new biomarker .

Many patient gene data can be stored in the system as described above. Along with the test results, genetic tests performed on each patient can also be stored. The results, and the gene data stored in the system, can be used to search for new biomarkers.

For example, in one non-limiting embodiment, once the 500 tests for a particular biomarker associated with a particular disease are performed, the system can retrieve a new biomarker for the same disease. The system can separate patients tested for disease into subgroups and search only those patients tested to find a particular biomarker because these patients are known candidates for disease.

By searching only the subgroups of patients tested for a particular biomarker associated with the disease, the search speed is much faster and more reliable. If you do not divide the population into specific subgroups, there is a lot of relevance that the system can return false positives. To prevent false positive returns, a very low p-value required by the Bonferonni Criteria is required, which may not be achievable. By using only the subgroups tested for a particular disease, the requirement is relaxed. For example, if there are 100 diseases tested, the p-value may be 100 times larger if subgroups are used than if no subgroups are used.

In some embodiments, a test for a new biomarker may be repeated each time a new test for a particular disease is ordered. This can be done to ensure the reliability of biomarkers found in the initial search, or to continue searching for new biomarkers. As each new test creates a larger subgroup of patients for retrieval, the search for new biomarkers becomes more reliable.

Without the system described herein, every time a new test is ordered and the biomarker search is repeated, all new patients will have to be compared to all patients in the subgroup. If 50 new tests are ordered for a particular biomarker or disease and there are 500 previous tests for the same biomarker or disease, then 50 new response tests will need to be performed, and each of the more than 500 patients will have millions Lt; / RTI > nucleotides. Testing will be very difficult. However, the system can be configured to determine the base pairs present at each genetic location for each patient, and determines the number of A base, C base, T base, and G base for each position. When a new test is ordered, the system can determine a new patient base pair at each position and add the base pair to the appropriate tally. For each new test, only one of the counts of each position needs to be updated. The updated tally may then be used to determine a correlation with a possible new biomarker. By aggregating base pairs in this manner, the system can increase the rate of retrieving new biomarkers by a factor equal to the total number of patients ordered. For example, if 500 patients have been tested for a particular disease, the search for new biomarkers may be 500 times faster using the system described herein. Instead of each correlation test being run for each of the 500 patients, only one test needs to be performed using the tally at each location.

In certain embodiments, each function for determining a new biomarker can occur in any module of the system. For example, the control server may create and update a patient list for each subgroup tested for a particular biomarker or disease; The gene data storage server can maintain and update the tally of base pairs at each location for each subgroup and the remote application can determine the correlation between the new biomarker and the disease. In another embodiment, the control server, the remote application, or the gene data storage server may each perform each of the tasks described. The position of each task is not important to the invention.

In some embodiments of the invention, the reason recording database can be configured so that the owner of the information of interest can enter this information in the reason recording database without disclosing this information to any other party. The system may allow the proprietary information owner to upload the proprietary information and the system may automatically encrypt the information to prevent other parties from accessing the uploaded information. In certain embodiments of the invention, encryption may be made so that even an operator of the entire system does not have access to information of reason. This system allows the owner of the proprietary information to perform a medical test on the information of the patient information storage server or the gene data storage server without having to disclose the proprietary information to the system or any party. In contrast to the known methods of using proprietary information in medical tests that require new gene sequencing each time a patient requests a test from another proprietary information owner, the system described herein provides a single gene The sequence can be obtained, and the owner of the information for all reason can execute the gene test using the single gene sequence.

Figure 16 illustrates a system configured to allow genetic or other medical testing for a patient using information of reason. A test laboratory 1501, such as an independent genetic testing service or any other patient clinical information source, may upload patient genetic information or other medical information to the patient information server 1502 as described herein. The information may be uploaded to the patient information server 1502 via a web portal 1515, an application, or by any method known in the art. The patient or clinician 1509 may then order a test on the information of the patient information server 1502, including a test that requires information of reason. In certain embodiments, the test request may be sent directly through the user interface associated with the system, or the request may be made through the patient's electronic health record or electronic medical record.

The proprietary information owner 1507 may upload the information needed to perform the test to the biomarker research data server 1504. [ The information may be entered via the web portal 1512 or other application. The application 1512 can automatically encrypt the uploaded information as shown in Figure 16 to ensure that no other party has access to this information. For example, a test for the SNP shown as 1510 may be encrypted as shown at 1511. [ Those skilled in the art will appreciate that other variations besides SNPs can be encoded in a similar manner. In certain embodiments, the system may include the option of allowing the proprietary information owner to inform the physician, patient, or payer party of the existence of a test of a particular cause that may be stored in the proprietary information marketplace 1503 have. This information may be sent to the physician or patient via the web portal 1518. [ The test results may be sent to the physician or patient via the application 1519.

In certain embodiments of the invention, testing may be performed by a program located on the biomarker research data server 1504. [ The program can automatically decrypt the information of the reason and can scan information in the patient data server 1502 for a particular patient using the information of reason. Since decryption and scanning are performed automatically by the system, no party need access to the information in the proprietary biomarker research data server 1504. That is, the biomarker research data server 1504 may serve as a black box, and the reason information is uploaded to the black box, used for medical tests, and not disclosed outside the black box.

In some embodiments of the invention, the encrypted information in the biomarker research data server 1504 may be in any form. In some embodiments of the invention, the encrypted information in the biomarker research data server is a list of specific locations in the gene sequence and a specific base pair within that position or positions corresponding to a particular result, . ≪ / RTI > In certain embodiments of the invention, the information in the biomarker research server 1510 may be a series of logical instructions for the system to perform. For example, the system can be ordered to determine the presence of a particular gene mutation in the patient ' s genome. If a mutation is present, then the system may be instructed to determine the presence of the second mutation, or to search the patient information database for specific medical information such as admission or symptoms. The system only outputs certain results from the test if all the logic steps are met.

In certain embodiments of the invention, the output of the test may take any form. In certain embodiments of the present invention, the output may be better suited to the particular patient as a result of the presence of the particular disease or condition, a risk factor corresponding to the probability that the patient will develop a particular disease or condition, or a genetic or other medical information of the patient. It may be the optimal course of treatment, such as the particular route of action of the drug to act on.

If the patient or physician 1509 orders a test of reason for information in the patient data server, the test price may be sent to the payor party 1506 via the web portal or application 1517. The payor party 1506 may pay through an application or portal 1516, which may be described by the biomarker escrow server 1505. [ The fee charged for using the reasoning test may be transmitted to the proprietary information owner 1507 via the application 1513 as described herein. The physician, the patient or the payer party do not need to view or access information of reason. The system can provide output to the user, but the user can not determine how to generate the output. Although shown as a different party in FIG. 16, those skilled in the art will appreciate that the patient may act as the payor party 1509.

In certain embodiments, the system may monitor and maintain control over payment, test use, available tests, or any other information via control server 1508 operating through a web portal or application 1514. [ In some embodiments, the system owner can receive any necessary payment and obtain any necessary data via the control server 1508. [ Those skilled in the art will understand that the owner of the system can set up the system so that it does not have access to unencrypted genetic test information.

Although the patient data server, the biomarker research data server, the biomarker marketplace server, and the biomarker escrow server are shown as separate servers in FIG. 16, those skilled in the art will appreciate that any two or more of these functions Lt; RTI ID = 0.0 > of < / RTI > Since the reasoned information is encrypted before entering the biomarker research data server, the party using the system can not access this information.

Although patient and causal information is generally described in terms of genetic information, those skilled in the art will appreciate that the system need not be limited to genetic information. In certain embodiments of the invention, the patient data may include any medical data of the patient, including medical history, demographic data, family history, and insurance information, Lt; / RTI > The condition or optimal treatment process represented by any patient information may be considered as information of concern by any party linking any patient information to the particular disease or optimal treatment process.

The encryption method used to encrypt the information of reason may be any encryption method known in the art. Non-limiting examples of encryption techniques that may be used include AES, Blowfish, CAST, GOST 28147-89, RC-6, Serpent and Twofish. Those skilled in the art will appreciate that there are other encryption methods that can protect the information of the reason for uploading to the system and are within the scope of the present invention.

Figure 17 illustrates an embodiment illustrating a process for encrypting a genetic test for use in the present invention. The proprietary information owner may enter a gene sequence (1601) corresponding to the results for the patient, including the location of a particular variant in the genome. The system may automatically encode the gene sequence and location information as a listing 1602. The encrypted sequence may then be transmitted to the proprietary data server 1603 as described herein. In certain embodiments of the invention, the encryption may be unidirectional encryption. The gene sequence and location data may be encrypted with an encrypted data string, but the encrypted data string can not be used to reproduce the original gene sequence. In certain embodiments of the invention, any method of the encoded gene sequence may be used. In certain embodiments of the present invention, loci of certain base pairs may be mixed during encryption to make decryption more difficult.

Figure 18 illustrates one embodiment of determining the presence or absence of a gene sequence in a patient ' s genome using an encrypted test. The encrypted genetic test 1702 may be retrieved from the proprietary data server 1701 and sent to the comparator 1703. The genetic information of the patient can be transmitted from the patient data server 1705 and the same encryption method as that used to encrypt the original genetic test is performed and generates a similar encrypted sequence 1704. The encrypted patient gene data may also be transmitted to the comparator 1703. The comparator 1703 may compare the two encrypted sequences to determine if the sequences match or whether the search logic of the genetic test is present in the patient sequence. In certain embodiments, the comparison may be performed by a scanning operation performed on the described system, and the comparator 1703 may be omitted.

Figure 19 shows a second method for determining the presence or absence of a gene sequence in a patient ' s genome using an encrypted test. In an embodiment of the invention using bi-directional encryption techniques, the encrypted genetic test 1802 stored in the proprietary data server 1801 may be decrypted when the patient or physician orders a test. The original gene sequence 1803 may be reconstructed upon transmission to the comparator 1804. The genetic information of the patient can be transmitted from the patient data server 1805 to the comparator 1804. The comparator 1804 may compare the two sequences to determine whether the two sequences match, or whether the search logic of the genetic test produces a match. Since the decryption is performed automatically by the system, no party can access the unencrypted genetic test 1802 while preserving the private nature of the information.

Those skilled in the art will appreciate that genetic testing need not be for a single part of the genome. Several parts of the same genome may be required to determine the effect of a genetic variation on a patient's health or treatment. In certain embodiments of the invention, using the same or different encryption techniques, a plurality of gene segments constituting a single test may be encrypted together, or multiple gene segments may be separately encrypted. Those skilled in the art will also appreciate that genetic testing may include logical instructions such as if, then instructions. This command can also be encrypted. The comparator determines if the first portion of the genome matches the test and then repeats the process to the second portion of the genome. In certain embodiments of the invention, a test may include any number of steps including 2, 3, 4, 5, or more steps to determine the result.

Although shown as separate components in Figs. 18 and 19, the comparator need not be a separate component. In certain embodiments of the invention, the comparator may be a patient data server, a biomarker server of interest, or a program designed to run on any other part of the system.

In some embodiments of the invention, the interface between the proprietary information owner and the system may be in the form of a web portal. The proprietary information owner can log in to the system and upload the proprietary information, and the system will automatically encrypt the information before placing it on the biomarker research server. The proprietary information owner may use the same web portal to track the use of the proprietary information and to pay for the use of the proprietary information or to collect royalties. In some embodiments of the present invention, the proprietary information owner may access information of the reason stored in the system. The proprietary information owner may be provided with a specific key for decrypting the information to add new information, update existing information, or remove information from the system. In certain embodiments of the present invention, the proprietary information owner may provide an option to allow one or more other parties access to proprietary information for purposes of, for example, obtaining FDA approval for testing or publicly disclosing information Lt; / RTI >

Although the genetic test system described herein has been described in terms of DNA information, such as germ cells or somatic DNA, the system is not limited to DNA information. Next-generation sequencing can be used to sequence RNA molecules that have been previously shown to reveal previously unknown transcripts and splicing isoforms and provide quantitative measurements of alternatively spliced isoforms. have. RNA sequencing extends the possibilities of research into the analysis of gene isoforms, translocation, nucleotide variation, and post-transcriptional base deformation. In certain embodiments of the invention, RNA information from the patient and proprietary or non-specific RNA testing information may be used in the described system.

In certain embodiments, RNA sequencing can be performed by generating cDNA molecules that are reversibly transcribed from the original RNA using known sequencing techniques. The relative abundance of individual transcripts, splice variants, isoforms, new transcripts and chimeric transcripts can be determined from mapped RNA sequences. Using RNA sequencing, qualitative data relating to the identity of mutations, transcription sites, expressed transcripts, and exon / intron boundaries can be used to identify differences in expression, selective splicing, selective TSS, and alternatives between two or more patients or treatments Lt; RTI ID = 0.0 > polyadenylation. ≪ / RTI > Each of these types of information may represent one or more genetic characteristics of a patient and may be included in the genetic test system described herein.

20 illustrates an example of how the system described herein can be implemented. The sample may be sent to sequencing laboratory 1901 to perform sequencing of the dielectric sample with sequencer 1902. The resulting sequence may be uploaded to the system 1907 via the bioinformatics pipeline 1908 using the application 1903 as described herein. As shown in FIG. 20, the sequence may be uploaded in the form of a FASTQ sequence, but one of ordinary skill in the art will appreciate that the gene sequence may be uploaded in any form known in the art.

A person or physician (1910) may request genetic testing for a genetic sample. As shown in FIG. 20, the request may be made as a prescription via the electronic medical record 1912 via the electronic medical record interface 1911, but the request may also be sent to the individual or physician via any method known in the art. Lt; / RTI > The request may be sent to the described system 1907 to perform a genetic test.

The proprietary rights holder 1904 may upload the information necessary to perform the genetic test from the proprietary database 1905 or any other source as described herein. The information of the reason may be encrypted using any known encryption method 1906 and uploaded to the system 1907. The encrypted information may be maintained in a "black box" 1908, as described herein, in order to preserve the nature of the information's nature. The system 1907 may perform a predefined test and return the results to the patient or physician 1910. As shown in FIG. 20, the results may be sent directly to the patient's electronic medical record 1912.

As shown in FIG. 21, the system described herein provides the ability to perform a number of tests on a patient. A number of databases 1905 containing the information necessary to perform the genetic tests can be uploaded to the system 1907, respectively, with a black box 1909 providing protection of the information of interest. In certain embodiments, multiple databases may come from a single proprietary information owner 1904 or from a number of proprietary information owners. The hospital or individual 1910 can generate multiple requests for patient gene testing with every request made through the single system 1907 described herein. As described, a plurality of genetic test requests may take the form of a prescription via interface 1911 from the patient's electronic medical record 1912. A single sample may be sequenced by laboratory 1901 and uploaded to system 1907. Any number of genetic tests using proprietary information can be performed using a single gene sequence. Because multiple tests can be performed on a single sequenced sample, the uploaded patient sequence is used as a single "information source" that performs genetic testing to reduce errors due to multiple sequences for the same patient.

Figure 22 illustrates a non-limiting example of a payment that may be described by the described system. Patient 1910 may pay for each genetic test performed, as indicated by arrow 1913. The sequencing laboratory 1901 may be paid for sequencing of the genetic sample as indicated by arrow 1915. [ The proprietary rights holder 1904 may be paid for the use of the proprietary information, as indicated by arrow 1914. In certain embodiments, as indicated by arrow 1916, sequenced data may be provided to the purported rights holder 1904 or researcher to determine a new possible genetic test.

In certain embodiments, testing of patient data may be performed by a standalone application as shown in FIG. The remote client or control server 2003 may receive a request to perform a medical test on the patient whose records are located in the patient record database 2001, The remote client or control server 2003 may invoke a standalone application 2002 that includes an instruction to perform a medical test, as indicated by the arrow 2005. In an optional embodiment, the stand-alone application 2002 may include all the instructions, scripts, or individual steps required to execute a set of medical tests or medical tests, such as genetic testing, without having to refer to a database such as GDIS have. In some embodiments, the standalone application 2002 may include only a portion of the instructions, scripts, or individual steps needed to perform a medical test or a collection of medical tests, and may receive additional information from a database (not shown in FIG. 23) You can request a command to complete a genetic test or test.

In an optional embodiment, the stand alone application 2002 may access the patient record database 2001 as indicated by arrow 2006 to obtain the patient record necessary to perform the requested test, such as the patient's gene sequence. The required patient record may be sent to the standalone application 2002 as indicated by arrow 2007. [ The standalone application 2002 can execute medical commands to execute medical tests. In certain embodiments, the stand alone application 2002 may generate test results as test notification documents or test result data. The test results may be sent to the remote client or control server 2003 as indicated by arrow 2008. [ In certain embodiments, the standalone application 2002 may additionally or alternatively transmit test results to a third party software or user (not shown). The test results may be sent to the original requestor by the remote client or control server 2003 as shown by the arrow 2010.

In certain embodiments, the RCA may be a standalone application as described herein, and may include instructions, scripts, or individual steps to execute a set of genetic tests or genetic tests without reference to a database. In certain embodiments, a remote client may include several instructions; Scripts, or genetic tests, or a set of genetic tests, and may require additional information or instructions from the database to complete genetic tests or tests. In certain embodiments, a remote client as a standalone application may generate a test notification document, or may be provided to other applications or users as test result data. In certain embodiments, the system may include a collection of precompiled or uncompiled software applications that can be invoked by an automated system, such as a user or RCA, to achieve one or more genetic tests.

24 illustrates a non-limiting embodiment of the use of an encrypted test by the described system. A third party test owner 2101, such as a proprietor of rights, may generate a new unencrypted test entry 2102 that may contain the information for the reason and an instruction to perform the medical test. Unencrypted test entry 2102 may be entered into the system via an API, web portal, script, or uploaded text file, as indicated by arrow 2106. The unencrypted test 2102 can be encrypted upon input to generate an encrypted test entry 2103 so that only the test creator can access the proprietary instructions as shown by arrow 2107. [ The encrypted test entry 2103 may be stored in the biomarker server 2105 as described herein. The encrypted test entry 2103 may be retrieved for each test by a remote client (not shown) as described herein, and may be used to perform a medical test by a remote client as shown by arrow 2108 .

In certain embodiments, the biomarker server may be located outside the system, as shown in FIG. The third party test owner 2201 may generate a new unencrypted test entry 2202, as indicated by arrow 2207. [ The unencrypted test entry 2202 may include instructions necessary to perform a medical test and interpret the results. The unencrypted test entry 2202 may be stored in the biomarker server 2203 as indicated by arrow 2208. [ In some embodiments, the unencrypted test entry 2202 may be encrypted before storing the test entry in the biomarker database 2203. In an optional embodiment, the unencrypted test entry may be encrypted and stored as an encrypted test entry 2205 after being stored in the biomarker server 2203.

When a medical test is requested, the encrypted test entry 2204 may be requested by the remote client or control server 2206 from the biomarker server 2203, as indicated by arrow 2209. [ The test may be requested by the remote client 2206 for each test and may be requested via an API, web portal, script or text file 2204. The encrypted test entry 2205 may be retrieved for each test through an API, web portal, script or text file 2204 and stored in a patient information database (not shown) by a remote client or control server 2206 Can be decoded and used to perform tests on the < / RTI >

The biomarker test system for the reasons described herein provides many advantages to all parties, some of which are shown in Figures 26-28. FIG. 26 shows a process in which a third party performs genetic research and gene sequencing. As shown in Fig. 26, a patient 2301 that has not yet undergone genome sequencing can cause its genome to be sequenced by a third party sequencer 2303. The patient ' s genome may be sequenced and stored in a proprietary biomarker test system 2305 as described herein. If desired, a physician or medical institution 2302 may request one or more genetic tests from the test system 2305, and a payment is made for each test. In certain embodiments, the doctor or medical institution 2302 may be associated with a third party sequencer 2303, but no association is required. A third party acting as a researcher or proprietary rights holder 2304 may store a genetic test of one or more causes in the system 2305 which may be encrypted to protect the information as described herein have. System 2305 may use genetic information to perform genetic testing and return results to physician 2302. [ To a third party for genetic sequencing performed by the third party laboratory service 2303 and for licensing fees or royalties for testing use of the reason from the third party research service 2304. [ The described system makes it possible for third parties to ensure that the information of reason is protected, while the information of reason can be used for genetic testing. Also, depending on the contract with the patient, the third party research service 2304 may obtain additional gene sequences from the patient 2301 to perform additional genetic studies.

As shown in FIG. 27, although gene sequencing is performed by the rights holder and other parties of the cause, the system creates several advantages. As shown in FIG. 27, the patient 2401 may have a genetic test performed by a fourth party laboratory 2403 that is not affiliated with a third party researcher 2405. The gene sequence of the patient may be stored in the patient data server as part of the test system 2404 for the reason described herein. The third party researcher or rights holder 2405 may upload the genetic test to the system 2404 as described herein. Physician 2402 or an individual may order a test through the described system 2404 as described herein, including testing a cause developed by a third party researcher or rights holder 2405. The sequencing laboratory 2403 may be paid for the sequencing service, while the rights holder 2405 may be paid royalties or licensing fees for the use of the proprietary test. The use of the single test system 2404 described herein allows a third party to access a customer of a different sequencing lab to provide additional royalty income without using existing assets. The sequencing laboratory and the physician to which it belongs have access to use third party genetic testing without the authority to reverse engineer the test.

Figure 28 illustrates the advantages of the described system for the patient 2501 that has already been sequenced and entered into the test system 2503. The physician may order a genetic test from the described system 2503, including the use of genetic testing for reasons previously entered into the system by a third party researcher or rights holder 2504. [ Thus, even if the genome has already been sequenced, the third party rights holder 2504 may obtain additional royalty income without using existing assets such as a genome sequencer. A system and method for encoding a script for querying a genetic sequence of a patient is shown in Fig. In particular, a method for generating a new biomarker script is shown in box 2601 of FIG.

In order to create a new biomarker script 2601, a new biomarker entry may be created 2604 in the biomarker script database 2602. In the biomarker script database 2602, SNPs linked to the biomarkers and related mutation lists can be generated (2605). An analysis list linked to the new biomarker may be generated in the biomarker script database 2602 (2606). The list of SNPs and related mutations may include information such as mutation values and where to look for sequences for mutations. The interpretation list may contain information such as risk factors based on each mutation and confidence interval for the combination of SNP mutations found. Biomarkers can combine mutations with various SNPs within or within the same gene to calculate a single risk value based on a combination of factors.

The biomarker script of the present invention provides advantages over tests that determine results based on protein or enzyme. Unlike protein or enzyme levels that can vary over time, the patient's genome is static. As a result, the patient's genome needs to be scanned only once. In contrast, tests measuring protein or enzyme levels may need to be repeated several times to account for changes in protein or enzyme levels. In addition, once the gene scan is complete, future biomarkers can be searched using the same gene scan.

In certain embodiments, the biomarker script may be equivalent to any known enzyme or PCR based diagnostic test kit. In the case of PCR-based test kits, this can be done using probes used by diagnostic test kits known as a list of SNPs in the biomarker script. In the case of enzyme tests, equivalence can be achieved by determining the identity of the expression quantitative trait loci (eQTL) corresponding to a particular enzyme or enzyme. eQTLs are regions of the genome that allow specific enzymes to be expressed. Enzyme-based testing can determine genetic disorders by measuring levels of enzymes in the patient's blood. The biomarker script of the present invention may instead search for a base mutation in the patient ' s genome that results in enzyme level discrepancies. In another embodiment, the biomarker script may be different from known diagnostic test kits.

Examples of SNPs and mutation lists associated with a particular biomarker for breast cancer are shown in Table 1. Each mutation shown in Table 1 corresponds to a specific position in the genome where the mutation is associated with an increased risk of breast cancer. A mutation is defined by the location of a mutation in a gene sequence, and the base at that position corresponds to an increased risk of disease. A list including positions, mutations, and matching criteria may be generated in the biomarker script database 2602.

An example of an interpretation list for the BRCA gene is shown in Table 2. The interpretation list can determine an increase in the risk of a particular disease, such as breast cancer, based on the mutations found in the patient's gene sequence. The risk factors in Table 2 are expressed in multiples that indicate increased risk from patients with mutations in the gene. Low and high confidence intervals represent 95% confidence levels of risk factors. Patients without definitively mutated SNPs have risk factor 1. Patients with one or more of the listed SNPs have a lifetime risk of high cancer risk. A list of unique interpretations for each available diagnostic test may be generated in the biomarker script database 2602.

In some embodiments, the list of SNPs in the biomarker script and analysis list may be the same as that provided by known or commercially available test kits. An example of a test kit such as Myraid Genetics' MammoPrint is available. The same SNPs retrieved by the test kit may be part of the SNP list of the present invention. The same interpretation provided by the test kit can be part of the interpretation list of the present invention. In this way, the encrypted biomarker script is identical to a known test kit.

Once the biomarker entry is generated as SNPs and an interpretation list, the system scans the sequence for the biomarker, as shown in box 2603 of FIG. At the start of scan 2607, a prescription for a particular gene sequence to be scanned is generated 2608. Based on the prescription, the system may retrieve a particular gene sequence from the gene sequence database 2609. [ The genetic sequence database may be a remote database separate from the biomarker script database 2602 in some embodiments. In other implementations, the gene sequence database may be local to the biomarker script database 2602. In some embodiments, either the gene sequence database or the biomarker script database 2602 may be embedded within another.

The biomarker information may be retrieved from the biomarker script database 2602 (2610). A list of SNPs and related mutations may be retrieved from the biomarker script database 2602 (2611). Using the list of SNPs, the system can scan the gene sequence and find the location of one of the SNPs (2612). The system can determine if a SNP is found in the gene sequence file 2613. [ Once the SNP is found in the gene sequence file, the system can then compare the base pairs at a particular position in the sequence to the mutation definition of the mutation list 2614. The system determines if a mutation is detected at the particular location 2615 and, if so, increases the positive mutation counter 2616. The system then determines if there are any other SNPs associated with the biomarker 2617. If there are any more SNPs associated with the biomarker, the system again determines if the next SNP in the gene sequence file 2613 is found. If no mutations are detected, or if no SNPs are found in the gene sequence file, the system may skip to step 2617 without increasing the positive mutation counter and determine whether there are any other SNPs associated with the biomarker Can be determined.

Once all of the SNPs associated with the biomarker are retrieved from the gene sequence, the system can retrieve the analysis list 2618 from the biomarker script database 2602. The system may retrieve the positive mutation counter value determined in step 2616 and find the corresponding risk value in the interpretation list 2619. [ The result may be returned 2620, and the process is terminated 2621. In certain embodiments, the results may include one or both of the risk factors and mutations detected in each SNP.

The physician can use the secure login described above to create a prescription. A screen shot step of creating a prescription is shown in Fig. The physician may enter a pseudo ID 2701 that allows the physician to access information in a specific sequence. The physician may also enter a patient ID 2702 that identifies the particular sequence to be tested. And a biomarker ID 2703 for determining a biomarker script to be used by the system. Finally, the doctor may enter whether this is a new or tumor specificity scan 2704. This tells the system whether a particular tumor is being scanned, which can determine which SNPs are specific. In some embodiments, the prescription may be automatically generated from the patient's electronic medical record. This may be done to automatically generate a prescription in the system using a third party application interface.

After the doctor has created the prescription, the system can automatically find the patient's gene sequence and the biomarker script needed. Upon retrieval of the sequence and biomarker script, the system may automatically scan the patient's sequence as described in FIG. A screen shot of the system during the search and scan process is shown in FIG. This screen may inform the physician that the requested patient sequence is present in the database as a file and the test is being executed or will be executed. Depending on the capacity of the system, the scanning process can be completed within 2 seconds.

Figure 32 shows a screen shot of the result output after performing a scan. Test results may be provided to the prescribing physician or to the patient. The output also includes the total risk factor 2801 and the 95% confidence interval 2802. In some embodiments, the output may also include a reference to be retrieved 2803, search results 2804 at these locations, mutation 2805, genotype found 2806, and criteria 1007 counted as a mutation. have. It is to be understood that not all of the information provided in Figure 32 need be included, and that any output that provides the results of a genetic test is within the scope of the present invention.

As can be seen in Fig. 32, the specific sample gene sequence did not show any positive reaction to any of the mutations shown in Table 1. Thus, the breast cancer risk factor of the patient based on the test is by definition IX.

An example of the output provided to a patient who is positive for some mutations is shown in FIG. As can be seen, the patient was positive at rs16942 (2901), rs766173 (2902) and rsl44848 (2903). Because three positive mutations were found, the system notified the risk factors in Table 2 for three mutations and returned that the patient's breast cancer risk factor was 1.75X and the 95% confidence interval was between 1.09X and 2.80X .

The next-generation sequencing technology has reduced the cost and time required to obtain the subject's gene sequence. These techniques generally use short readout data to determine the subject's gene sequence. Next-generation sequencing techniques typically use short sequences between 10 and 100 base pairs. Due to the short reading sequence used in next generation sequencing, the technique can not reliably detect large mutations in the gene sequence.

Structural modifications of gene sequences can adversely affect the subject's health. Figure 34 shows the type of mutation that can lead to an increased risk of disease. The deletion of the base pair is indicated by 3001. The original sequence 3006 included a base pair T 3008 in the sequence. The mutated sequence 3007 does not include a base pair 3008. Insertion of a base pair is indicated by 3002. The original sequence 3009 can be transformed into a mutated sequence 3010 by insertion 3011 of base pairs. The mutation of the base pair is indicated by 3003. The original sequence 3012 includes a base pair T (3014). The mutated sequence has a base pair G (3015) at this position. These mutations lead to base pairs in gene sequences that are different from the typical base pairs at the same position. The number of copies is represented by 3004. The original sequence 3016 repeats the base pair ACTA 3018 twice. The mutated sequence 3017 repeats the base pair 3018 four times. Replication number variation can be caused by structural rearrangements of the genome such as deletion, replication, inversion, and translocation. Low replication iteration is particularly sensitive to these genomic rearrangements resulting in replication number variation. Factors such as size, orientation, percent similarity, and distance between copies affect the susceptibility of low copy repetition to genome rearrangements that result in copy number variation.

The translocation is indicated by 3005. A portion 3023 of the sequence 3019 is switched by a corresponding portion 3024 of the complementary sequence 3020. The result is a mutated sequence 3021, 3022, and the portions 3023, 3024 are translated into a complementary sequence. The reversal is indicated by 3029. The original sequence 3025 has a base pair denoted 3027 as an ATC. The mutated portion of the sequence 3026 has this portion reversed as the CTA 3028. Those skilled in the art will appreciate that any of the mutations described herein may comprise a sequence that is larger than that shown in FIG. Insertion, deletion, copy number variation and translocation can include sequences of hundreds or thousands of base pairs in length.

Table 3 shows an abbreviated list of some large structural variations known to cause disease. Those skilled in the art will appreciate that this is not a complete list. Any embodiment of the present invention is directed to the detection of any structural variation, including those known to cause cancer, neurodegenerative disease, cardiovascular disease, mood disorders, or any other Mendelian genetic disease that can be diagnosed from germline DNA .

Since next generation sequencing can not reliably detect a variation of a gene sequence that is significantly larger than the read length used for sequencing, additional techniques are needed to determine if there is a large structural variation in the decoded sequence using short read data.

Certain gene structural variations are inherited along with other covalent parameters. That is, large insertions or deletions tend to be inherited along with other structural variations that can be more easily detected with next generation sequencing techniques. Thus, the presence of a covalent parameter can be used as a predictor of a large structural variation. These covariant parameters can be more easily detected in sequenced genomes by next generation sequencing techniques. It is therefore possible to predict the presence of large structural variations that can not be easily detected in sequenced genomes by next generation sequencing techniques based on covalent parameters that can be more easily detected. These covariant parameters can provide a useful method of detecting larger variations even when preparing the original sequence using small read data. Covariant parameters may be insertion, deletion, duplication, replication number variation, inversion and translocation of any arbitrary size.

As described herein, certain parameters can be covalent with large structural variations that can cause disease. There are several techniques that can be used to determine these parameters. One non-limiting technique that can be used to determine covariant parameters with large structural variations is machine learning. Machine learning is a technique in which a computer determines a pattern in a complex system. For example, traditional genetic sequencing techniques can be used to sequence all or part of multiple genomes to determine if there is a large structural variation. The computer can be programmed to scan these genomes to determine if there are other parameters in the genome that are positive for large structural variations that do not exist in the genome that are negative for large structural variations. After identifying parameters that are present only in genomes that are positive for a particular large structural mutation, or that are present in as many unequal numbers of genomes that are positive for large structural mutations, the computer has learned covariant parameters Can be mentioned. Those skilled in the art will appreciate that other methods of determining covalent parameters can be used.

Figure 35 illustrates steps that may be taken to identify covariant parameters. As described herein, the machine learning 3101 can be used as an identification source for the parameter 3104 to be cauterized. In certain embodiments, a document search 3102 may be performed to identify a parameter 3104 that has been determined to be covariant with a large structural variation. In addition, a study of reason (3103) may be performed to further identify the covariate parameter (3104). The study of reason (1603) may include searching for a patent or patent application or any other public or private data source. Once the crotch parameter 3104 is identified, the system can be configured to query the genetic sequence to retrieve these parameters, thereby identifying large structural variations in the sequenced gene sequence with short read data.

After identifying a parameter that can be covalent with a large structural variation, a second genome set, with or without a large structural variation, may be queried for the identified covariate parameter. This is important for testing the predicted value of the identified parameter. If the system properly identifies whether each second genome set includes a large structural variation, then the identified parameter can be used to predict the presence of a large variation. Those skilled in the art will appreciate that there are other techniques that can be used to identify covalent parameters with large structural variations. Any technique for determining covalent parameters is contemplated by the present invention.

If a covalent parameter is identified with a large structural variation that can not be easily detected by a next generation sequencing technique using short reading data, a new genetic test for this large structural variation can be generated. New genetic tests will retrieve parameters that can be detected with next generation sequencing technology using short read data, so new tests can be performed on genomes sequenced with short read data. This allows fast, inexpensive and reliable genetic testing for a variety of diseases.

The query of the gene sequence for the covalent parameter can be performed as described herein. In certain embodiments, any of the query, storage, or payment functions of the described systems may be used to determine the presence of large structural variations using covariant parameters. An algorithm using the identified covariate parameters can be added to the query module described herein to determine the presence of large structural variations in the sequenced genome using short read data.

The system described herein enables the centralization of silico tests for standardized and consistent high quality testing without the need for the use of disposable kit based assays. In addition, the systems and methods described herein enable the development of computational methods for analyzing short read sequence data obtained from next generation sequencing techniques for difficult-to-identify mutations.

Example 1

Here, an example of how to determine covariance parameters that are covalent with the BRCA gene mutation is provided. Many DNA samples of triple negative breast cancer can be obtained in the laboratory. Assuming a combined occurrence frequency of BRCA mutations in the sample is 30%, the probability of obtaining at least one sample with BRCA mutation will be at least 99.9% if at least 30 samples are obtained. Additional DNA sample sets may be reserved for later testing. Samples may be de-identified and may be accompanied by co-variate information such as sex, diet, body mass index and race, as well as complete diagnostic and therapeutic history. A significant number of existing BRCA mutations should be 6 kb exon 13 founder mutation duplication.

Commercially available BRCA analytical tests such as Myriad BART (BRAC Analysis Large Reerrangement test) may be performed for each sample. In addition, samples can be sequenced using any sequencing platform, such as Illumina's sequencing platform. Sequencing can target regions of chromosome 13 and 17 that are encoded for the BRCA gene, including a region of 10 kb adjacent to the gene.

As a result of the BART test, a large set of genomic variations present in the sample can be identified. The test results may be a set of original images, processed sequence files, mapped sequences, and invoked variations. The processed sequence file can be analyzed to identify the genomic features of the BART test with one-to-one correspondence with next-generation sequencing heterogeneous calls. The analysis can be done by executing a sequence file processed through a set of sorting and invocation tools such as GATK or Tuxedo. Those skilled in the art will appreciate that the same methodology may be used to identify any structural insertions that represent insertion, deletion, mutation, translocation, or any genetic disease.

The system described herein is not limited to analysis of germline DNA. In certain embodiments, the systems and methods described can be used for the analysis of somatic cell cancer cell DNA. As described herein, mutations present in somatic cell cancer cell DNA can have dramatic effects on efficacy for cancer treatment. The systems and methods described herein can be used in mutagenesis calls for somatic cell tumor cell DNA. In certain embodiments, the system can use any cell sample to test for mutations. The system may utilize primary or metastatic tumor tissue. In addition, the system can use tumor tissue or circulating tumor cells. In certain embodiments, the system can utilize samples characterized by microneedle aspiration biopsy, tumor heterogeneity over a wide range of necrosis, mutation and other genetic abnormalities, and a much lower proportion of tumor DNA than viable tumor tissue. Because the next-generation sequencing technology is highly sensitive, NGS sequencing can be used with samples where only a small proportion of the total DNA extracted from the sample is mutated. However, as described herein, the NGS sequencing technique can not easily detect many larger structural variations. As such, the methods and systems described herein can be used for mutation calls in somatic cell tumor cell DNA sequenced using short read data, by identifying and using covariate parameters as described herein.

An example of a procedure for testing somatic cell cancer DNA is shown in Fig. The healthcare provider may be able to biopsy the cancerous tumor in step 3201. Tumor DNA may be sequenced at step 3202 or at any DNA sequencing facility. A tumor DNA sequence and any other biological information may be added to the patient record database as described herein at step 3203. [ In step 3204, the tumor cell DNA sequence may be queried for a relevant mutation or other biomarker as described herein for patient germline DNA. The required payment to the rights holder, server owner, and application owner for any reason from the payer party may be processed and described at step 3205. [ A clinical report may be generated by the system as described herein at step 3206 to determine the presence of any relevant mutations or other biomarkers of the tumor cell DNA sample.

The systems and methods described herein may be used for diagnosis or for accompanying diagnosis. As an example of a companion diagnostic genetic test, BRCA1 and BRCA2 assays are currently being used in ovarian cancer patients to determine patients who can be treated with Lynparza ™ (olaparib). Certain mutations in the patient's germline DNA or somatic cell tumor cell DNA can inform the physician of the cause of the current or future symptoms affecting the patient. Querying tumor cell DNA samples may be particularly useful for the purpose of accompanying diagnosis. As described herein, certain mutations present in tumor cells can have a significant effect on the efficacy of a particular therapy. By determining what mutations are present in the tumor cells, the physician can better tailor treatment for individual patients.

In any embodiment, regardless of the source of the genetic information, the system may operate as shown in FIG. The test and diagnostic system 3301 may communicate with the physician 3304, the laboratory 3302, the insurer 3305 and the rights holder 3306. In certain embodiments, doctor 3304 may prescribe genetic test 3307 for patient 3302, including whole genome sequencing, germ cell DNA testing or somatic cell tumor cell DNA testing. The patient may have a DNA sample 3308 sequenced by a hospital or laboratory 3302. [ The sequenced data may be forwarded to system 3301 (3309). The physician 3304 may inform the system of the specific genetic test to be performed (3310). Actual prescriptions for a particular test 3310 may be sent directly by the physician 3304, or in some embodiments, via the patient's electronic medical record. The system may perform genetic tests 3318 using the algorithms described herein to generate test results 3319. [ The test results may be sent to the physician 3304 either directly or through the patient's electronic medical record (3311). The physician may use the results to treat patient 3303 more efficiently (3312).

To facilitate payment, the system 3301 may communicate the test 3313 to be performed to the insurer or payer party 3305. Any necessary fees for use of the biomarkers in question in the test may be transferred from the insurance company 3305 to the system 3301 (3314). The system may obtain information about the biomarker 3317 of interest from the rights holder 3306. [ As described herein, a given test or series of tests may include two or more rights holders. As such, the system can obtain the necessary information from any number of rights holders 3306. [ Based on the test, the system may notify the insurer 3305 of the costs associated with the genetic test execution 3315, including licensing costs or any service charges. The system may collect such a fee 3316 from the insurance company 3305. [ The system may also notify rights holder 3306 of any reasoned information used in test 3320 and may describe any required licensing fees 3321. [ Any service charge for system use may also be described (3322).

38 shows a simplified flow diagram of one embodiment of the present invention using electronic health records or electronic medical records. A prescription for test 3401 may be sent to the patient's electronic health record or electronic health record 3402. [ The application 3403 may obtain the necessary information from the patient's electronic record 3402 to perform the genetic test. The system can then process the prescription 3404 to determine the patient involved in the required genetic testing and testing. The second application 3406 may send the necessary information from the processed prescription to the genome scanning application 3407. [ Genomic scanning application 3407 may obtain genetic information directly via a database or application 3408. [ The results of the genetic test can be sent back to the processing system for analysis and visualization (3409). The interpreted result may be sent back to the patient's electronic health record or electronic medical record 3402 via application 3403. [ Where the results may be presented to the patient or physician via electronic or electronic medical records (3410).

In certain embodiments of the invention, the transmission of data and patient information can comply with all applicable standards for patient ' s privacy and security. In particular, because prescribing and outcome notifications for genetic testing can be performed entirely within electronic medical records, the system provides an efficient mechanism for transferring information in a manner that complies with HIPPA or Health Level Seven (HL7) standards.

The systems and methods described herein can provide a single point for genetic information that can be stored, queried and accessed as required by a patient or physician. Using a single point or a single database for raw genetic information does not require large genomic data to be sent electronically over the Internet, making possible a much faster and more efficient genome scanning process. Requests to scan the genome for specific structural changes can be received via the API as described herein. The API processes the request and allows the described system to scan the database's genome and return the results. In certain embodiments, the scan request and the results may be transmitted through the patient's electronic health record or electronic medical record. The patient's genetic data may remain in the database without the need to transmit data over the Internet.

In addition, even without a single central repository of gene data, the laboratory can perform sequence queries on different patient gene sequences and conclude other results. The systems and methods described herein also enable patient gene sequences and diagnostic scan records to be consistently available, discoverable, and understandable. To achieve this goal, electronic medical records should include a smooth gene prescription function supported by a structured data format resulting from automated clinical decisions, machine-processing and HL7 and ONC standardization efforts.

The systems and methods described herein permit the development and support of electronic gene test orders between the electronic medical records and the system of the present invention. The systems and methods described herein also allow genetic test delivery within electronic medical records. Applications described for the interface between physician, test and licensing may allow for smooth interoperability between the system, hospital system, insurer, and clinician of the present invention in accordance with all applicable standards such as HL7, FHIR or any other standard .

In particular, the present invention provides a federal, state, and federal agency that can develop an institution, an electronic health record vendor, a laboratory, a standards development agency, a health information exchange and a laboratory ordering interface, develop implementation guidance, Or information transfer between the main organs can be facilitated. Because the system described herein can serve as a single point for gene storage and testing, the present invention is uniquely positioned for the development of standards and custom interfaces.

The software implementing the process may be coded in any language known in the art. This includes ASP, APS.NET, Java, JavaScript, C, C ++, C #, .NET, Objective C, F #, F # .NET, Basic, VB.NET, Go, Python, Perl, Hack, PHP, But are not limited to, Erlang, XHP, Scala, Ruby, J2EE, SQL, CGI, HTTP, or XML.

It will be apparent to those skilled in the art that various combinations and / or modifications and variations can be made in the system in accordance with a particular operating request. Also, features shown or described as part of one embodiment may be used in other embodiments to obtain another embodiment.

100: System
101: Trusted server
103: Processor
105: patient record database
110: Historical database of reason

Claims (53)

As a system,
A control server in communication with a remote application providing a result of the genetic test;
A record database of the reason for communicating with the control server and including a record of the rights holder of the biomarker and / or the biomarker of the cause; And
A genetic data storage server < RTI ID = 0.0 >
Lt; / RTI >
The remote application sends and receives data to perform the genetic test,
Wherein the control server sends and receives data to account for payment to the rights holder from the payer party. The method according to claim 1,
Further comprising a black box containing information of an encrypted reason for carrying out a genetic test, wherein the remote application is located with a genetic data storage server. The method according to claim 1,
Wherein the control server is configured to account for the payment to the owner of the gene data storage server for storage of the gene data. The method according to claim 1,
The remote application communicating with the scanning application, the scanning application configured to perform the genetic test, and the control server configured to account for the payment to the owner of the scanning application based on the genetic test. The method according to claim 1,
Wherein the control server is configured to receive a request for a genetic test from a third party. The method according to claim 1,
Wherein the control system is configured to determine a requested genetic test for more than one patient, and wherein the control system is configured to generate a subgroup of patients, wherein the subgroup of patients are patients for which the same genetic test is requested. The method according to claim 6,
Wherein the gene data storage server or remote application is configured to determine an association between genetic information and genetic information at a particular genetic location for more than one patient. 8. The method of claim 7,
Wherein the gene data storage server or remote application generates a tally of base pairs for each of more than one patient at one or more genetic locations and wherein the tally comprises a number of patients each having a base pair at at least one genetic location . 9. The method of claim 8,
Wherein each time a new test is ordered for a genetic disease, the system updates the base pair tally with a base pair for the new patient. 10. The method of claim 9,
Each time a new test is ordered for an inherited disease, the genetic data storage server or remote application determines the association between the genetic information and the genetic information at each of one or more genetic locations for one or more patients. As a system,
And a control server in communication with a black box containing an encrypted medical database from a first user,
The control server communicates with at least one remote application,
Wherein the remote application communicates with at least one patient record database containing data relating to the one or more patients,
Wherein the remote application is configured to query the patient record database based on information in the encrypted medical database to provide an output of the query. 12. The method of claim 11,
Wherein the encrypted medical database can not be decrypted by any other user. 12. The method of claim 11,
Wherein the control server and the patient record database are not co-located. 12. The method of claim 11,
Wherein the encrypted database comprises information about genetic mutations and / or biomarkers. 12. The method of claim 11,
Wherein the encrypted database contains information about a history. 12. The method of claim 11,
Wherein the system is configured to receive a set of allowed users from the first user and to allow decryption of the database by the set of allowed users. 12. The method of claim 11,
Wherein the system is configured to receive a request for a medical test by the requesting party using information in an encrypted database and wherein information in the encrypted database is not provided to the requesting party. 12. The method of claim 11,
Wherein the system is configured to allow the first user to update data in the encrypted database. 12. The method of claim 11,
Wherein the patient record database comprises at least one patient ' s genetic information. 12. The method of claim 11,
Wherein the control server is configured to electronically receive a plurality of encrypted medical databases from one or more users. 21. The method of claim 20,
Further comprising a research data server for reasoning, wherein each encrypted medical database is stored in a research data server for a reason. 12. The method of claim 11,
Further comprising an encryption program configured to encrypt the medical database before the server in question has received the encrypted medical database. 12. The method of claim 11,
The system further comprising a prescription application that communicates with a remote application, wherein the prescription application is configured to receive a prescription for a medical test, and the prescription application is configured to transmit a prescription to a remote application. 24. The method of claim 23,
Wherein the prescription for a medical test comprises information necessary for identifying a record in a patient record database corresponding to a patient whose medical test is prescribed. As a system for performing genetic testing,
A biomarker script database,
The biomarker script database includes at least one biomarker entry corresponding to the biomarker, the biomarker entry includes an analysis list corresponding to the gene mutation list and the gene mutation definition list corresponding to the biomarker, Includes risk factors based on variant definitions,
Wherein the biomarker script database is configured to communicate with a patient record database comprising patient identification information for at least one patient, and a portion of the genome or genome for at least one patient. 26. The method of claim 25,
Determining the identity and number of genetic mutations present in the genome corresponding to the biomarker and identifying a portion of the genome or genome based on the biomarker script in order to provide risk factors associated with the mutations present in the genome based on the analysis list Further comprising a black box having an application configured to search for a genetic test. 27. The method of claim 26,
A biomarker script is a system for performing genetic tests that are equivalent to known diagnostic tests. 26. The method of claim 25,
A system for performing a genetic test, the system further comprising a privacy agency capable of establishing rules to control user access to any records generated by any privacy facilitating system or by any database accessible by a privacy facilitating system. 26. The method of claim 25,
Wherein the system further comprises a history database containing information about rights holders for one or more proprietary biomarkers, the system being configured to retrieve the historical history database and to determine if the biomarker is a biomarker of interest A system for performing a test. 30. The method of claim 29,
And a payment institution that is configured to explain the payment from the payer party to the rights holder if the biomarker is a biomarker of a particular nature. 27. The method of claim 26,
Wherein the system is configured to obtain a prescription for a genetic test and the application configured to search for a portion of the genome or genome is configured to receive a prescription for genetic testing and perform a search based on the prescription for genetic testing / RTI > 32. The method of claim 31,
Wherein the system is configured to receive a prescription for genetic testing from an electronic health record. 26. The method of claim 25,
Wherein the patient record database is remote from the biomarker script database. As a method for performing a genetic test,
Creating a biomarker entry in the biomarker script database;
Encoding a single nucleotide polymorphisms and a mutation definition list corresponding to a biomarker entry in a biomarker script database, the single nucleotide polymorphism and mutation definition list being associated with a biomarker entry;
Encoding an interpretation list in a biomarker database, wherein the interpretation list is associated with a biomarker entry and the interpretation list provides a risk factor for the disease based on a mutation in a single nucleotide polymorphism and a mutation definition list;
Scanning a portion of the genome or genome of the patient to determine the presence of the mutation definition; And
Providing a risk factor corresponding to the determination of the presence of a mutation definition
/ RTI > wherein the method comprises the steps of: 35. The method of claim 34,
Accessing a patient record in a patient record database, wherein the patient record database is configured to communicate with a biomarker script database, wherein the patient record comprises a portion of the patient's genome or genome and patient identification information; And
Limiting the information contained in the patient record database such that one or more information fields are not available to one or more users of the genetic test system
RTI ID = 0.0 > 1, < / RTI > 35. The method of claim 34,
Accessing a record database of reasons including a record of the proprietor's biomarker and the proprietor of the proprietary biomarker;
Using a biomarker script to scan a patient record database and a history record database to determine the presence of a biomarker of a cause in the patient record of the patient record database, and generating a result set comprising at least one result record;
Selectively updating a patient record database to include identification of a biomarker of interest;
Automatically transferring the information obtained from the query to one or more of the rights holder user and the payer party user associated with the biomarker for the reason used in the query of the patient record database; And
Step describing the payment or escrow between the rights holder user and the payer party user of the biomarker for the reason used in the scan
RTI ID = 0.0 > 1, < / RTI > 35. The method of claim 34,
A biomarker script is a method for performing a genetic test that is equivalent to a known diagnostic test. 35. The method of claim 34,
Wherein the information in the patient record is filled by a diagnostic service provider or by a physician. 35. The method of claim 34,
Wherein the information delivered to the rights holder user does not include patient identification information in the patient record that includes the biomarker of interest in the diagnostic information. 35. The method of claim 34,
The step of scanning the patient ' s genome or a portion of the genome to determine the presence of the mutation definition,
Obtaining a prescription for the patient's genome or a portion of the genome; the prescription includes a patient identifier, a gene sequence identifier, and a biomarker identifier;
Searching for a single nucleotide polymorphism and mutation definition list in the biomarker script database corresponding to the biomarker identifier;
Scanning the patient ' s genome or a portion of the genome for each mutation definition; And
Determining the number of mutations present in the genome or part of the genome
≪ / RTI > 35. The method of claim 34,
Wherein the analysis list provides a risk factor based on a plurality of mutations found corresponding to the mutation definition. 35. The method of claim 34,
Further comprising the step of counting the number of mutations found in the genome or part of the genome corresponding to the mutation definition. 35. The method of claim 34,
Providing a list of each mutation found in the genome or part of the genome corresponding to the mutation definition. 44. The method of claim 43,
Wherein the step of obtaining a prescription for a genome or a portion of a genome comprises obtaining a prescription through an electronic medical record of a patient. As a system for performing genetic testing,
A biomarker script database,
The biomarker script database includes at least one biomarker entry corresponding to the biomarker, the biomarker entry includes an analysis list corresponding to the biomarker and a variation definition list corresponding to the biomarker, and the analysis list includes a single nucleotide Including risk factors based on polymorphisms and mutation definitions,
Wherein the biomarker script database is configured to communicate with a patient record database comprising patient identification information for at least one patient, and a portion of the genome or genome for at least one patient. 46. The method of claim 45,
Determining the identity and number of genetic mutations present in the genome corresponding to the biomarker and identifying a portion of the genome or genome based on the biomarker script in order to provide risk factors associated with the mutations present in the genome based on the analysis list Wherein the system further comprises an application configured to search for a genetic test. 47. The method of claim 46,
A biomarker script is a system for performing genetic tests that are equivalent to known diagnostic tests. 46. The method of claim 45,
Further comprising a privacy authority capable of setting a rule that controls user access to any record created by the privacy promotion system or any database accessible by the privacy promotion system. 46. The method of claim 45,
Wherein the system further comprises a history database containing information about rights holders for one or more proprietary biomarkers, the system being configured to retrieve the historical history database and to determine if the biomarker is a biomarker of interest A system for performing a test. 50. The method of claim 49,
And a payment institution that is configured to explain the payment from the payer party to the rights holder if the biomarker is a biomarker of a particular nature. 47. The method of claim 46,
Wherein the system is configured to obtain a prescription for a genetic test and the application configured to search for a portion of the genome or genome is configured to receive a prescription for genetic testing and perform a search based on the prescription for genetic testing / RTI > 52. The method of claim 51,
Wherein the system is configured to receive a prescription for genetic testing from an electronic health record. 46. The method of claim 45,
Wherein the patient record database is remote from the biomarker script database.

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