TWI856681B - Deep learning-based automatic detection and identification system and method for chromosomes in karyotype diagrams - Google Patents
Deep learning-based automatic detection and identification system and method for chromosomes in karyotype diagrams Download PDFInfo
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Abstract
本發明係提供一種基於深度學習之核型圖染色體自動偵測辨識方法及系統,其係能夠機器學習建立一染色體自動偵測辨識模型,進而能夠直接針對染色體原圖進行其內染色體之特徵擷取及分類,以有效地減少臨床人員花費於影像判斷上之時間。The present invention provides a method and system for automatic detection and identification of chromosomes in a karyotype image based on deep learning, which can establish a chromosome automatic detection and identification model through machine learning, and then directly extract and classify the features of the chromosomes in the original chromosome image, so as to effectively reduce the time spent by clinical personnel on image judgment.
Description
本發明係有關於遺傳分子辨識系統,特別係指一種基於深度學習之核型圖染色體自動偵測辨識系統及方法。 The present invention relates to a genetic molecular identification system, and in particular to a karyotype chromosome automatic detection and identification system and method based on deep learning.
按,染色體是細胞內具有遺傳性質的聚合體,是遺傳信息(基因)的主要載體。正常人類之染色體數量為46條,含有22對體染色體與1對性染色體,染色體異常會引起染色體疾病,所謂染色體異常係包含染色體數目異常或是結構異常。而染色體疾病會導致智力低下、發育畸型、性別分化異常、癌症、不孕等等。 Chromosomes are genetic aggregates in cells and are the main carriers of genetic information (genes). Normal humans have 46 chromosomes, including 22 pairs of chromosomes and 1 pair of sex chromosomes. Chromosomal abnormalities can cause chromosomal diseases, which include abnormalities in the number of chromosomes or abnormalities in their structure. Chromosomal diseases can lead to mental retardation, developmental malformations, abnormal sex differentiation, cancer, infertility, etc.
根據統計,一般產前胎兒中約有2%會發生染色體異常症,因此,染色體核型分析成為目前產前篩檢中之重要項目。目前臨床進行染色體核型分析需要醫生或是醫檢師親自進行染色體圖片之判讀,並一個受檢者至少會提供4張染色體圖片,使得染色體核型分析造成醫療人力上之負擔。雖然目前已有開發自動染色體分析系統來取代人工分析,惟,現有自動染色體分析系統係以圖像編輯軟體為基礎,不僅準確度不高,並且分析過程中仍需要體檢人員全程參與,以致於仍無法達到降低檢測時間成本及人力成本之問題。 According to statistics, about 2% of prenatal fetuses will have chromosomal abnormalities. Therefore, chromosome karyotype analysis has become an important item in prenatal screening. Currently, clinical chromosome karyotype analysis requires doctors or medical examiners to personally interpret chromosome images, and a subject will provide at least 4 chromosome images, which makes chromosome karyotype analysis a burden on medical manpower. Although automatic chromosome analysis systems have been developed to replace manual analysis, the existing automatic chromosome analysis systems are based on image editing software. Not only is the accuracy low, but the analysis process still requires the participation of medical examiners, so it is still impossible to reduce the time cost and labor cost of testing.
本發明之主要目的係在於提供一種基於深度學習之核型圖染色體自動偵測辨識方法及系統,其係能夠透過機器學習模組生成一染色體自動偵測辨識模型,藉此能夠自動地偵測且識別染色體圖樣中各對染色體,以達到降低染色體核型分析之檢測成本。 The main purpose of the present invention is to provide a method and system for automatic detection and identification of chromosomes in karyotype diagrams based on deep learning, which can generate a chromosome automatic detection and identification model through a machine learning module, thereby automatically detecting and identifying each pair of chromosomes in the chromosome diagram, so as to reduce the detection cost of chromosome karyotype analysis.
是以,為能達成上述目的,本發明係提供一種基於深度學習之核型圖染色體自動偵測辨識方法,其係透過一處理器使用儲存在一數據庫中之電腦可讀指令來執行,而主要包含有下列步驟: Therefore, in order to achieve the above-mentioned purpose, the present invention provides a method for automatic detection and identification of karyotype chromosomes based on deep learning, which is executed by a processor using computer-readable instructions stored in a database and mainly includes the following steps:
步驟A:選擇一染色體訓練圖集,其內包含對應各對染色體之複數特徵圖。 Step A: Select a chromosome training atlas containing multiple feature maps corresponding to each pair of chromosomes.
步驟B:將該染色體訓練圖集輸出至一機器學習模型中,進行第一階段物件偵測,意即偵測染色體訓練圖集中之各對染色體並進行框選,並分析各對染色體之框選結果,以生成識別各對染色體之一第一預測框。 Step B: Output the chromosome training atlas to a machine learning model to perform the first stage of object detection, that is, detect and select each pair of chromosomes in the chromosome training atlas, and analyze the selection results of each pair of chromosomes to generate a first prediction frame to identify each pair of chromosomes.
步驟C:分別將各對染色體之該些第一預測框輸出至以一第二物件偵測模型進行分析,該第二物件偵測模型係偵測染色體訓練圖集中之各對染色體並調整該第一預測框,生成識別各對染色體之一第二預測框。 Step C: Output the first prediction frames of each pair of chromosomes to a second object detection model for analysis. The second object detection model detects each pair of chromosomes in the chromosome training atlas and adjusts the first prediction frame to generate a second prediction frame for identifying each pair of chromosomes.
步驟D:以該些對應各對染色體之第二預測框及其對應之染色體序號作為參數,生成一染色體自動偵測辨識模型,用以自動辨識及分類一待測染色體圖樣中至少一對染色體。 Step D: Using the second prediction frames corresponding to each pair of chromosomes and their corresponding chromosome numbers as parameters, a chromosome automatic detection and recognition model is generated to automatically identify and classify at least one pair of chromosomes in a chromosome pattern to be tested.
更進一步來說,由於藉由染色體自動偵測辨識模型係能夠用以快速且準確識別一待測染色體圖樣之各對染色體,並加以分類,因此,本發明所揭該基於深度學習之核型圖染色體自動偵測辨識方法係更包含有一步驟E,其中,該步驟E係將一待測染色體圖樣輸出至該染色體自動偵測辨識模型,該染色體自動偵測辨識模型偵測並框選該待測染色體圖樣中之染色體,且識別所框選之染色體的染色體序號,以生成一識別結果。 Furthermore, since the chromosome automatic detection and recognition model can be used to quickly and accurately identify each pair of chromosomes in a chromosome pattern to be tested and classify them, the karyotype chromosome automatic detection and recognition method based on deep learning disclosed in the present invention further includes a step E, wherein the step E is to output a chromosome pattern to be tested to the chromosome automatic detection and recognition model, and the chromosome automatic detection and recognition model detects and selects the chromosomes in the chromosome pattern to be tested, and identifies the chromosome numbers of the selected chromosomes to generate an identification result.
於本發明之實施例中,該步驟A中之該些特徵圖係擷取自一染色體原圖,具體來說,將一染色體原圖輸出至一圖像標記軟體,該圖像標記軟體於該染色體原圖中標記各對染色體,並依據標記進行裁切及染色體序號分類後,即可得到該些特徵圖。 In the embodiment of the present invention, the feature images in step A are captured from a chromosome original image. Specifically, a chromosome original image is output to an image marking software, and the image marking software marks each pair of chromosomes in the chromosome original image, and after cutting and classifying the chromosome serial numbers according to the marks, the feature images can be obtained.
為能即時提升本發明所揭染色體自動偵測辨識模型識別性能,於本發明之一實施例中係更包含有一步驟F,係指當一回饋訓練模型偵測到一對染色體具有2個以上之第二預測框時,且該些第二預測框之重疊率係高於一預定IOU閾值時,該待測染色體圖樣輸入至該染色體訓練圖集,並且再次執行步驟B至D。 In order to improve the recognition performance of the chromosome automatic detection and recognition model disclosed in the present invention in real time, one embodiment of the present invention further includes a step F, which means that when a feedback training model detects that a pair of chromosomes has more than two second prediction frames, and the overlap rate of these second prediction frames is higher than a predetermined IOU threshold, the chromosome pattern to be tested is input into the chromosome training atlas, and steps B to D are executed again.
於本發明之實施例中,為能得到較佳之識別效果,故於該染色體訓練圖集輸出至該第一物件偵測模型前,對該些特徵圖之至少一部進行一圖像前處理程序,如調整尺寸、亮度或方向等。 In the embodiment of the present invention, in order to obtain a better recognition effect, before the chromosome training atlas is output to the first object detection model, at least a portion of the feature maps is subjected to an image pre-processing procedure, such as adjusting the size, brightness or direction, etc.
為能增加臨床上使用便利度及應用性,於該步驟E中,將該識別結果輸入至一影像後處理模型,該影像後處理模型係自該待測染色體圖樣進行如去背、排序、位置校正等後處理。 In order to increase the convenience and applicability of clinical use, in step E, the recognition result is input into an image post-processing model, and the image post-processing model performs post-processing such as background removal, sorting, and position correction on the chromosome image to be tested.
於本發明又一實施例中係揭露一種基於深度學習之核型圖染色體自動偵測辨識系統,其主要包含有一數據庫及一處理器,其中,該數據庫,至少儲存有複數染色體特徵圖;該處理器係與該數據庫間傳輸數據,並且透過機器學習模組生成一染色體自動偵測辨識模型,再透過該自動辨識模組辨識一待測染色體圖樣中之各對染色體並加以分類,以生成一識別結果。 In another embodiment of the present invention, a deep learning-based karyotype chromosome automatic detection and identification system is disclosed, which mainly includes a database and a processor, wherein the database at least stores a plurality of chromosome feature maps; the processor transmits data with the database, and generates a chromosome automatic detection and identification model through a machine learning module, and then identifies and classifies each pair of chromosomes in a chromosome pattern to be tested through the automatic identification module to generate an identification result.
其中,機器學習模組,具有一機器學習模型,並於本發明之一實施例中,該機器學習模型係包含有二階段物件偵測程序。 The machine learning module has a machine learning model, and in one embodiment of the present invention, the machine learning model includes a two-stage object detection process.
於本發明之另一實施例中,該機器學習模組中更包含有一回饋訓練模型,用以透過一預定IOU閾值,判斷框選於同一對染色體之二預測框是否應 該被保留,並且將該染色體圖樣及其判斷結果回饋至機器學習模組,以即時更新該染色體自動偵測辨識模型,達到提升染色體自動偵測辨識模型辨識性能之功效。 In another embodiment of the present invention, the machine learning module further includes a feedback training model for judging whether two prediction frames selected for the same pair of chromosomes should be retained through a predetermined IOU threshold, and feeding back the chromosome pattern and its judgment result to the machine learning module to update the chromosome automatic detection and recognition model in real time, thereby achieving the effect of improving the recognition performance of the chromosome automatic detection and recognition model.
於本發明之次一實施例中,該處理器係更包含有一影像前處理模型,其係接收來自該數據庫之染色體特徵圖,並進行一影像前處理程序,如旋轉、鏡像、裁切、亮度調整等。 In the next embodiment of the present invention, the processor further includes an image pre-processing model, which receives the chromosome feature map from the database and performs an image pre-processing procedure, such as rotation, mirroring, cropping, brightness adjustment, etc.
於本發明之另一實施例中,該處理器更包含有一影像後處理模型,其係接收經由該染色體自動偵測辨識模型完成偵測及辨識之待測染色體圖樣,並根據一影像處理指令對該辨識結果進行影像後處理。 In another embodiment of the present invention, the processor further includes an image post-processing model, which receives the chromosome pattern to be detected and identified by the chromosome automatic detection and identification model, and performs image post-processing on the identification result according to an image processing instruction.
本發明係揭露一種基於深度學習之核型圖染色體自動偵測辨識方法及系統,其係能夠機器學習建立一染色體自動偵測辨識模型,而透過該染色體自動偵測辨識模型,係能夠直接針對染色體原圖進行其內染色體之特徵擷取及分類,不僅能夠有效地減少臨床人員花費於影像判斷上之時間,更能提升對於困難圖相之識別準確率。 The present invention discloses a method and system for automatic detection and identification of chromosomes in karyotype images based on deep learning. It is capable of establishing a chromosome automatic detection and identification model through machine learning. Through the chromosome automatic detection and identification model, the features of the chromosomes in the original chromosome image can be directly extracted and classified. This can not only effectively reduce the time spent by clinical personnel on image judgment, but also improve the recognition accuracy of difficult images.
術語「數據」,又可被理解為「資料」、「訊息」,係指可被識別或處理之符號、檔案、指令、文字、數字等。 The term "data" can also be understood as "information" or "information", which refers to symbols, files, instructions, text, numbers, etc. that can be identified or processed.
術語「機器學習」,係會以一機器學習模型於資料中進行學習以及改善,尋找到模式與關連,並根據其學習及分析結果制訂出決策與預測。 The term "machine learning" refers to using a machine learning model to learn and improve in data, find patterns and relationships, and make decisions and predictions based on its learning and analysis results.
術語「染色體圖像」或「染色體原圖」,係自來自染色體檢體所得之核型圖,原則上,各核型圖中具有22對體染色體加上1對性染色體,其中,臨床上係依據染色體的大小,大致分為9個群組:A、B、C、D、E、F、G、X與Y,其中被分為A組群的大型染色體為A1、A2、A3、B4與B5;尺寸最小的組群為G、X及Y。 The term "chromosome image" or "chromosome original map" refers to the karyotype diagram obtained from the chromosome specimen. In principle, each karyotype diagram has 22 pairs of somatic chromosomes plus 1 pair of sex chromosomes. Clinically, the chromosomes are roughly divided into 9 groups based on their size: A, B, C, D, E, F, G, X and Y. The large chromosomes in group A are A1, A2, A3, B4 and B5; the smallest groups are G, X and Y.
而本發明所指染色體圖樣被判定為正常者,係代表染色體圖像中之各對染色體結構及特徵係無異常;本發明所指染色體圖樣被判定為異常者,係指染色體圖樣中之各對染色體結構或/及特徵有病變、增生、斷裂、折疊、或是無法判讀等情形,例如第5或21對染色體增生、染色體圖樣中受到雜質遮擋過多特徵、或於觀察過程中無法完全排除異染色體群者。 The chromosome pattern determined as normal in the present invention means that the structure and characteristics of each pair of chromosomes in the chromosome image are normal; the chromosome pattern determined as abnormal in the present invention means that the structure and characteristics of each pair of chromosomes in the chromosome image are pathological, hyperplastic, broken, folded, or cannot be interpreted, such as hyperplasia of the 5th or 21st pair of chromosomes, too many features in the chromosome pattern are blocked by impurities, or heterochromosomal groups cannot be completely excluded during the observation process.
術語「特徵圖」,係指透過一圖形特徵處理模組自一染色體原圖中提取各對染色體之特徵所得之結果。 The term "feature map" refers to the result obtained by extracting the features of each pair of chromosomes from a chromosome original map through a graphic feature processing module.
術語「機器學習」,係指處理器會透過演算法來識別輸入數據集之模式,並透過該模式建立出一資料模型。 The term "machine learning" refers to the process whereby a processor uses an algorithm to identify patterns in an input data set and build a data model based on the patterns.
術語「模組(Module)」,係指由一個或數個基礎功能元件組成的特定功能組件,一般來說,模組會包含有模組輸入介面、模型(Model)及其代碼說明,而透過模組輸入介面將數據或資料輸入至模型後,再執行該模型而得到一個結果。 The term "module" refers to a specific functional component composed of one or more basic functional components. Generally speaking, a module includes a module input interface, a model, and its code description. After inputting data or information into the model through the module input interface, the model is executed to obtain a result.
術語「模型」,又可被理解為代碼,為一種電腦可讀指令而得於電腦或處理器上被執行。 The term "model" can also be understood as code, which is a computer-readable instruction that is executed on a computer or processor.
術語「序號」或「染色體序號」,係指染色體的編號,例如第1對染色的序號為1,依此類推。 The term "sequence number" or "chromosome sequence number" refers to the number of the chromosome, for example, the first pair of chromosomes is number 1, and so on.
術語「IOU(intersection over union)」,係指預測的物件區域與真實物件區域之交集,以本發明來說,IOU係以下式計算而得:IOU=二框重疊之面積/二框面積之總和。 The term "IOU (intersection over union)" refers to the intersection of the predicted object area and the real object area. In the present invention, IOU is calculated by the following formula: IOU = the area of the overlap of two frames / the sum of the areas of two frames.
術語「校正」或「位置校正」,係指能夠識別染色體之著絲粒,並將染色體短臂位置調整為於著絲粒上方,且長臂位置調整為著絲粒下方。 The term "correction" or "position correction" refers to the ability to identify the centromere of a chromosome and adjust the position of the short arm of the chromosome to be above the centromere and the long arm to be below the centromere.
本發明之一實施例係提供一種基於深度學習之核型圖染色體自動偵測辨識方法,其係藉由一系統執行,而該系統係主要包含有一數據庫及一處理器,其中:該數據庫係用以儲存資料及/或數據,包含有複數染色體原圖、複數染色體特徵圖、複數電腦可讀指令等。 One embodiment of the present invention provides a method for automatic detection and identification of chromosomes in a karyotype diagram based on deep learning, which is executed by a system, and the system mainly includes a database and a processor, wherein: the database is used to store data and/or data, including multiple chromosome original images, multiple chromosome feature maps, multiple computer-readable instructions, etc.
該處理器係與該該數據庫間得以無線或有線之方式傳輸資料或/及數據內之資料執行機器學習模型並進行染色體核型體之自動偵測辨識。具體來說,該處理器係至少包含有一輸入/輸出模組、一機器學習模組及一自動辨識模組,其中:該輸入/輸出模組係用以與該數據庫間傳輸數據及/或資料,並得將之輸入至該機器學習模組或該自動辨識模組。 The processor can transmit data and/or data in the database wirelessly or wiredly to execute the machine learning model and perform automatic detection and recognition of chromosome karyotype. Specifically, the processor includes at least an input/output module, a machine learning module and an automatic recognition module, wherein: the input/output module is used to transmit data and/or data with the database, and can input it into the machine learning module or the automatic recognition module.
該機器學習模組係具有一機器學習模型,而該機器學習模型係接收該數據庫之一部染色體特徵圖,進行該些染色體特徵圖中之物件偵測程序,再從中提取出各對染色體之序號及其預測框,並將各對染色體之預測框及其序號作為參數,以生成一染色體自動偵測辨識模型。 The machine learning module has a machine learning model, and the machine learning model receives a part of the chromosome feature graphs of the database, performs object detection procedures in the chromosome feature graphs, extracts the sequence number of each pair of chromosomes and its predicted frame, and uses the predicted frame of each pair of chromosomes and its sequence number as parameters to generate a chromosome automatic detection and recognition model.
該自動辨識模組係接收一待測染色體圖樣及該染色體自動偵測辨識模型,透過將該待測染色體圖樣輸入至該染色體自動偵測辨識模型,以識別該待測染色體圖樣內各對染色體,生成一識別結果。 The automatic identification module receives a chromosome pattern to be tested and the chromosome automatic detection identification model, and identifies each pair of chromosomes in the chromosome pattern to be tested by inputting the chromosome pattern to be tested into the chromosome automatic detection identification model to generate an identification result.
於本發明之一實施例中,該機器學習模型中係包含二階段物件偵測,意即先對該些染色體特徵圖進行第一階段物件偵測,並將第一階段物件偵測結果再進行第二階段物件偵測,以得到各對染色體之序號及其預測框。 In one embodiment of the present invention, the machine learning model includes two-stage object detection, that is, firstly, the first-stage object detection is performed on the chromosome feature graphs, and then the second-stage object detection is performed on the first-stage object detection results to obtain the sequence number of each pair of chromosomes and its prediction frame.
於本發明之另一實施例中,該機器學習模組係更包含有一回饋訓練模型,其係透過一預定IOU閾值,判斷框選於同一對染色體之複數預測框何種應保留,並且將該染色體圖樣及其判斷結果回饋至機器學習模組,作為再次訓練之訓練資料集,以生成新的染色體自動偵測辨識模型。 In another embodiment of the present invention, the machine learning module further includes a feedback training model, which determines which of the multiple prediction frames of the same pair of chromosomes should be retained through a predetermined IOU threshold, and feeds the chromosome pattern and its judgment result back to the machine learning module as a training data set for retraining to generate a new chromosome automatic detection and recognition model.
本發明之一實施例中,該處理器係更包含有一影像後處理模型,其係接收經由該染色體自動偵測辨識模型完成偵測及辨識之待測染色體圖樣,並根據一影像處理指令對該辨識結果進行影像處理,如擷取特定序號之染色體或含有其之圖片、去除所選取圖片或特定區域之背景,調整色調、校正染色體之位置、依據所識別之染色體序號進行圖像中所有染色體之排序等。 In one embodiment of the present invention, the processor further includes an image post-processing model, which receives the chromosome pattern to be detected and identified by the chromosome automatic detection and identification model, and performs image processing on the identification result according to an image processing instruction, such as capturing chromosomes with specific serial numbers or images containing them, removing the background of the selected image or specific area, adjusting the color tone, correcting the position of the chromosome, and sorting all chromosomes in the image according to the identified chromosome serial numbers.
本發明之另一實施例中,該處理器係更包含有一影像前處理模型,係於染色體特徵圖輸入至該機器學習模型前,對該些染色體特徵圖之至少一張進行如圖像增廣(Efficient Det Resize Crop)之圖像前處理程序。 In another embodiment of the present invention, the processor further includes an image pre-processing model, which performs an image pre-processing procedure such as image augmentation (Efficient Det Resize Crop) on at least one of the chromosome feature maps before the chromosome feature maps are input into the machine learning model.
更進一步來說,本發明於實施例中所揭基於深度學習之核型圖染色體自動偵測辨識方法係包含有下列步驟: Furthermore, the method for automatic detection and identification of chromosomes in karyotype diagrams based on deep learning disclosed in the embodiments of the present invention includes the following steps:
步驟101:選擇一染色體訓練圖集,其內包含對應各對染色體之複數特徵圖,其中,各對染色體之特徵圖係將一染色體原圖輸出至一圖像標記軟體,如imagelaber軟體,該圖像標記軟體於該染色體原圖中標記各對染色體,並依據標記進行裁切及染色體序號分類後所得者。 Step 101: Select a chromosome training atlas, which contains multiple feature maps corresponding to each pair of chromosomes, wherein the feature map of each pair of chromosomes is obtained by outputting a chromosome original image to an image labeling software, such as imagelaber software, and the image labeling software labels each pair of chromosomes in the chromosome original image, and then performs cropping and chromosome number classification according to the labels.
步驟102:該染色體訓練圖集進入機器學習模組前,先將該些特徵圖輸入至影像前處理模組進行圖像增廣處理,具體來說,當特徵圖超過設定之尺寸時,先將超出部分裁切掉,再進行旋轉、鏡像、亮度調整等處理;當特徵圖未超過設定之尺寸時,則不需要進行裁切及後續影像前處理程序。 Step 102: Before the chromosome training atlas enters the machine learning module, the feature maps are first input into the image pre-processing module for image augmentation processing. Specifically, when the feature map exceeds the set size, the excess part is first cut off, and then rotation, mirroring, brightness adjustment and other processing are performed; when the feature map does not exceed the set size, there is no need to perform cutting and subsequent image pre-processing procedures.
步驟103:將該染色體訓練圖集輸出至一機器學習模型中,進行第一階段物件偵測,意即偵測並框選各特徵圖中之染色體,並分析框選結果,以生成對應各對染色體之該第一預測框生成各對染色體之序號及用以框選各對染色體之一第一預測框。 Step 103: Output the chromosome training atlas to a machine learning model to perform the first stage object detection, that is, detect and select the chromosomes in each feature graph, and analyze the selection results to generate the first prediction frame corresponding to each pair of chromosomes, generate the sequence number of each pair of chromosomes and a first prediction frame for selecting each pair of chromosomes.
步驟104:將該些第一預測框輸出至以一第二物件偵測模型進行分析,根據分析結果調整該第一預測框之位置或/及尺寸,生成各對染色體之序號及用以框選各對染色體之一第二預測框。 Step 104: Output the first prediction frames to a second object detection model for analysis, adjust the position and/or size of the first prediction frame according to the analysis results, generate the serial number of each pair of chromosomes and a second prediction frame for selecting each pair of chromosomes.
步驟105:以該些第二預測框及其對應之染色體序號作為參數,生成一染色體自動偵測辨識模型,用以自動辨識及分類一待測染色體圖樣中至少一對染色體。 Step 105: Using the second prediction frames and their corresponding chromosome numbers as parameters, a chromosome automatic detection and recognition model is generated to automatically identify and classify at least one pair of chromosomes in a chromosome pattern to be tested.
步驟106:將一待測染色體圖樣輸出至該染色體自動偵測辨識模型,該染色體自動偵測辨識模型係偵測且框選該待測染色體圖樣中之各對染色體,並標示所框選之染色體的染色體序號,生成一識別結果。 Step 106: Output a chromosome pattern to be tested to the chromosome automatic detection and recognition model. The chromosome automatic detection and recognition model detects and selects each pair of chromosomes in the chromosome pattern to be tested, and marks the chromosome numbers of the selected chromosomes to generate an identification result.
步驟107:依據一使用者指令,將該識別結果輸入至一影像後處理模型,進行識別結果之後處理,具體來說,該自該識別結果中擷取含有特定序號之染色體對之圖片,並將除特定序號之染色體外的其他物件去除;或是將各對染色體進行位置校正;或是將該些染色體依據其序號大小進行排序。 Step 107: According to a user instruction, the recognition result is input into an image post-processing model to perform post-processing of the recognition result. Specifically, the image containing the chromosome pair with a specific serial number is extracted from the recognition result, and other objects except the chromosome with the specific serial number are removed; or the position of each pair of chromosomes is corrected; or the chromosomes are sorted according to the size of their serial numbers.
步驟108:當一識別結果中之任一對染色體具有2個以上之第二預測框時,該識別結果會輸入至該回饋訓練模型,以分別比較各該第二預測框及真實框之IOU與一預定IOU閾值之大小,並根據比較結果判斷得以保留之第二預測 框,而當保留之第二預測框數量大於等於2時,則將複數個第二預測框融合為單一第二預測框,並將該染色體圖樣及判斷結果輸入至該染色體訓練圖集,並且再次執行步驟102至105,以生成新的染色體自動偵測辨識模型。 Step 108: When any pair of chromosomes in a recognition result has more than 2 second prediction frames, the recognition result will be input into the feedback training model to compare the IOU of each second prediction frame and the true frame with a predetermined IOU threshold, and determine the second prediction frame to be retained based on the comparison result. When the number of retained second prediction frames is greater than or equal to 2, multiple second prediction frames are merged into a single second prediction frame, and the chromosome pattern and judgment result are input into the chromosome training atlas, and steps 102 to 105 are executed again to generate a new chromosome automatic detection and recognition model.
其中,該預定IOU閾值通常會依據染色體大小而設定,如第1-5對染色體及第13-16對染色體係分別屬於大型及中型染色體,其預定IOU閾值設定為0.7;而其他小型染色體,如第19-22染色體,其預定IOU閾值則會設定為0.5或0.6。 The predetermined IOU threshold is usually set according to the size of the chromosome. For example, the 1st to 5th pair of chromosomes and the 13th to 16th pair of chromosomes are large and medium-sized chromosomes, respectively, and their predetermined IOU threshold is set to 0.7; while other small chromosomes, such as the 19th to 22nd chromosomes, have their predetermined IOU thresholds set to 0.5 or 0.6.
更進一步來說,於步驟108中,該些第二預測框彼此不相交或是尺寸相同而造成IOU為零時,則該回饋訓練模型係會根據該些第二預測框之中心點間相距之距離、各該第二預測框之長、寬等數值納入判斷參數。 Furthermore, in step 108, when the second prediction frames do not intersect each other or have the same size and the IOU is zero, the feedback training model will incorporate the judgment parameters based on the distance between the center points of the second prediction frames, the length and width of each second prediction frame, etc.
其中,於本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法係於Res2Net101及BiFPN所組成之骨幹網路中生成特徵圖,再透過one stage及two stage組成之二階段物件偵測架構得到各對染色體之預測框及其對應之預測得分。 Among them, the deep learning-based automatic detection and identification method of karyotype chromosomes disclosed in the present invention generates a feature map in the backbone network composed of Res2Net101 and BiFPN, and then obtains the prediction frame of each pair of chromosomes and its corresponding prediction score through a two-stage object detection framework composed of one stage and two stage.
以下,為能驗證本發明之技術特徵所能達成之功效,將茲舉下列實例並搭配詳細說明如後。 In order to verify the effects that can be achieved by the technical features of the present invention, the following examples are given with detailed explanations.
實例一:資料處理 Example 1: Data processing
本實例中所使用之染色體原始圖檔係來自於台中榮民總醫院婦女醫學部基因實驗室;染色體檢體來自孕婦中的胎兒之羊水,共5000張,229852條染色體,其中,每張染色體原始圖檔都有對應之一核型圖。 The original chromosome image files used in this example come from the Genetic Laboratory of the Department of Women's Medicine, Taichung Veterans General Hospital; the chromosome samples come from the amniotic fluid of the fetus of the pregnant woman, a total of 5,000 images, 229,852 chromosomes, among which each original chromosome image file has a corresponding karyotype map.
於進行機器訓練前,須針對各染色體原始圖檔進行以下標記處理,而成為染色體圖樣:由受過醫檢師訓練與驗收之人員依據每條染色體的特徵進行識別,並與標準核型圖進行核對,以確保準確性;在每張染色體圖像的末尾,檢查 染色體的數量是否準確;通過另一個標記檢查每條染色體的注釋,並確認染色體的總數量是否正確;其中,注釋染色體圖像之工具為Matlab中的imagelaber軟體,儲存格式為gTruth或xml檔,而xml係由gTruth轉換而來者。 Before machine training, each chromosome original image file must be marked and processed as follows to become a chromosome image: a person who has received medical training and acceptance will identify each chromosome based on its characteristics and check it against the standard karyotype map to ensure accuracy; at the end of each chromosome image, check whether the number of chromosomes is accurate; check the annotation of each chromosome through another marker and confirm whether the total number of chromosomes is correct; the tool for annotating chromosome images is the imagelaber software in Matlab, and the storage format is gTruth or xml file, and xml is converted from gTruth.
經由染色體圖像係依據3:1之比例隨機分為訓練資料集及測試資料.aa集中之染色體圖樣分為困難及簡單,如表2所示,其中,困難圖像之判斷標準為:(1)染色體重疊,尤其是超過兩條以上之重疊;(2)顏色黯淡,特徵不清晰;(3)染色體過於細長。 The chromosome images were randomly divided into training data set and test data according to the ratio of 3:1. The chromosome images in the aa set were divided into difficult and simple, as shown in Table 2. The judgment criteria for difficult images are: (1) chromosome overlap, especially overlap of more than two chromosomes; (2) dull color and unclear features; (3) chromosomes are too thin and long.
實例二:訓練參數與性能測試結果 Example 2: Training parameters and performance test results
在訓練時的參數設定上,迭代優化方式為Adaptive Moment Estimation(ADAM);batchsize的大小為1;初始學習率等於warm up的最佳學習率;另外為防止過擬合,只要當前驗證總損失值超過先前驗證總損失值5次,則停止訓練。於在Focal loss的部分,將正樣本權重設為0.6,負樣本權重為0.4。 In the parameter setting during training, the iterative optimization method is Adaptive Moment Estimation (ADAM); the batch size is 1; the initial learning rate is equal to the best learning rate of warm up; in addition, to prevent overfitting, as long as the current validation total loss value exceeds the previous validation total loss value by 5 times, the training is stopped. In the focal loss part, the weight of positive samples is set to 0.6 and the weight of negative samples is set to 0.4.
以1250張染色體圖樣作為測試資料集,並以不同骨幹架構作為特徵提取網路,檢測本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統之性能,結果如表3及表4所示。 Using 1250 chromosome images as the test data set and different backbone architectures as the feature extraction network, the performance of the karyotype chromosome automatic detection and identification method and system disclosed in the present invention based on deep learning is tested. The results are shown in Tables 3 and 4.
表3中FPN為FEATURE PYRAMID NETWORK之縮寫;BiFPN為Weighted Bi-directional Feature Pyramid Network之縮寫;MULTI-IOU為多尺度 IOU,係會對不同大小的染色體採取不同的IOU閾值;DIOU為Distance-IOU loss之縮寫;GIOU為GIOU_Loss之縮寫。 In Table 3, FPN is the abbreviation of FEATURE PYRAMID NETWORK; BiFPN is the abbreviation of Weighted Bi-directional Feature Pyramid Network; MULTI-IOU is multi-scale IOU, which takes different IOU thresholds for chromosomes of different sizes; DIOU is the abbreviation of Distance-IOU loss; GIOU is the abbreviation of GIOU_Loss.
表3所使用之驗證方法採用COCOAPI的mAP,參照測試集的真實數值來驗證與計算準確度,意即所使用之性能評估指標包含有mAP(IOU=0.5)、抓取率(Recall)、精準度(Precision)與F1指數(F1 score),其中,mAP是基於COCOAPI之mAP50所計畫,如下式(1)與式(2),並測框與真實框之間應以IOU=0.5(包含0.5)作為判斷標準,以確認預測框架是真(True);Recall則是以下式(3)計算所得者;精準度是以下式(4)計算所得者;而TP為預測框與真實框皆是真;TN為預測框與真實框皆是假;FP為預測框為真但真實框為假;FN為預測框為假但真實框為真。 The verification method used in Table 3 adopts the mAP of COCOAPI, and verifies and calculates the accuracy with reference to the real value of the test set, that is, the performance evaluation indicators used include mAP (IOU=0.5), capture rate (Recall), precision (Precision) and F1 index (F1 score). Among them, mAP is planned based on the mAP50 of COCOAPI, as shown in the following formulas (1) and (2), and the IOU between the measured frame and the real frame should be 0.5 (including 0.5) as the judgment standard to confirm that the predicted frame is true (True); Recall is calculated by the following formula (3); Precision is calculated by the following formula (4); and TP means that both the predicted frame and the real frame are true; TN means that both the predicted frame and the real frame are false; FP means that the predicted frame is true but the real frame is false; FN means that the predicted frame is false but the real frame is true.
AP.50=AP(IOUTH=Multi)...(1) AP. 50= AP ( IOUTH = Multi )...(1)
由表3之結果可知,本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統無論於何種骨幹網路下皆具有良好辨識性能,準確率超過98%,其中,又以使用Res2Net101+BiFPN+MULTI-IOU+DIOU之骨幹網路者的抓取率更高,意即對於困難圖像之辨識性能更佳。 From the results in Table 3, it can be seen that the method and system for automatic detection and recognition of karyotype chromosomes based on deep learning disclosed in the present invention has good recognition performance regardless of the backbone network, with an accuracy rate of over 98%. Among them, the backbone network using Res2Net101+BiFPN+MULTI-IOU+DIOU has a higher capture rate, which means that the recognition performance for difficult images is better.
由表4之結果可知被分類為大型染色體之A1、A2、A3、B4與B5能夠獲得較高之準確度;而小型染色體,如G、X、Y組群則因於染色體圖樣中較容易被大型染色體覆蓋,準確度較低。 From the results in Table 4, we can see that A1, A2, A3, B4 and B5 classified as large chromosomes can obtain higher accuracy; while small chromosomes, such as G, X, and Y groups, are more likely to be covered by large chromosomes in the chromosome pattern, so the accuracy is lower.
請參圖1及圖2,當訓練資料集數量為800張時,準確率開始逐漸提高;在2000張圖像時,準確率達到98.87%;於3200張圖像時,準確率係達到98.87%;於5000張圖像時,準確率達到98.91%。當數據量與準確度穩定後,設置150個epoch,每10個epoch進行驗證,紀錄每次準確度與總損失,得知於epoch100時能得到最佳性能,性能水準達98.91%。 Please refer to Figure 1 and Figure 2. When the number of training data sets is 800, the accuracy begins to gradually increase; when it is 2000 images, the accuracy reaches 98.87%; when it is 3200 images, the accuracy reaches 98.87%; when it is 5000 images, the accuracy reaches 98.91%. When the amount of data and accuracy are stable, set 150 epochs, verify every 10 epochs, record the accuracy and total loss each time, and find that the best performance can be obtained at epoch 100, with a performance level of 98.91%.
實例三:實際測試 Example 3: Actual test
於本實例中係選取簡單、困難及高度困難的染色體圖像,如圖3至圖5所示,其中,圖3係為簡單染色體圖樣,染色體重疊與黏合都相當少,且染色體大小適中,特徵清晰;圖4為困難染色體圖樣,重疊與黏合染色體數量上升, 染色體彎曲方向更多變;圖5為高度困難染色體圖樣,樣重疊與黏和染色體數量大幅上升,染色體更加多變,甚至有染色體與雜質重疊。 In this example, simple, difficult and highly difficult chromosome images are selected, as shown in Figures 3 to 5. Figure 3 is a simple chromosome image, with very little chromosome overlap and adhesion, and the chromosome size is moderate and the features are clear; Figure 4 is a difficult chromosome image, with an increase in the number of overlapping and adhesion chromosomes, and the chromosome bending direction is more varied; Figure 5 is a highly difficult chromosome image, with a significant increase in the number of overlapping and adhesion chromosomes, more variable chromosomes, and even chromosomes overlapping impurities.
將該3張染色體圖樣分別由本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統進行識別,並且識別結果經由醫檢師評估準確度。由評估結果可知,本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統針對簡單染色體圖像具有100%之準確度;對於困難染色體圖像具有98%之準確度;對於高度困難染色體圖像具有90%之準確度。 The three chromosome images were identified by the deep learning-based karyotype chromosome automatic detection and identification method and system disclosed in the present invention, and the accuracy of the identification results was evaluated by a medical examiner. From the evaluation results, it can be seen that the deep learning-based karyotype chromosome automatic detection and identification method and system disclosed in the present invention has 100% accuracy for simple chromosome images; 98% accuracy for difficult chromosome images; and 90% accuracy for highly difficult chromosome images.
實例四:與其他模型之比較 Example 4: Comparison with other models
對於其他物件偵測模型:Faster-RCNN、YOLOv4、Retinanet、Swin-transformer、YOLOR與Centernet++分別使用實例一所揭資料集進行訓練與測試,並將結果與本發明所揭染色體自動偵測辨識模型與進行辨識性能之比較,結果如表5所示。 For other object detection models: Faster-RCNN, YOLOv4, Retinanet, Swin-transformer, YOLOR and Centernet++, the data set disclosed in Example 1 is used for training and testing respectively, and the results are compared with the chromosome automatic detection and recognition model disclosed in the present invention to perform recognition performance. The results are shown in Table 5.
由表5之結果可知,相較於其他模型來說,本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統於四項指標皆表現較佳,意即能夠有效地區分染色體與背景,並能夠進行正確分類,以能夠達到具有較高準確度之優點。 From the results in Table 5, it can be seen that compared with other models, the method and system for automatic detection and identification of karyotype chromosomes based on deep learning disclosed in the present invention performs better in all four indicators, which means that it can effectively distinguish chromosomes from the background and can perform correct classification, so as to achieve the advantage of having a higher accuracy.
又,將本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統與另一模型:DeepACEV2(H.Bai,T.Zhang,C.Lu,W.Chen,F.Xu,and Z.-B.Han,"Chromosome extraction based on U-Net and YOLOv3,"IEEE Access,vol.8,pp.178563-178569,2020.)進行性能比較,所使用之訓練方式都相同,結果如表6所示;並且,比較本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統與DeepACEV2識別困難圖像之準確度,結果如表7所示,其中,DeepACEV2將重疊的染色體視為困難圖像,根據物件的IOU來找出重疊染色體並計算其準確度,而本發明所定義之困難圖樣係採取臨床上醫檢師之標準,因此相較於DeepACEV2來說,本發明所進行判斷之困難圖像之難度係較高。 In addition, the method and system for automatic detection and identification of chromosomes in karyotype images based on deep learning disclosed in the present invention are combined with another model: DeepACEV2 (H.Bai, T.Zhang, C.Lu, W.Chen, F.Xu, and Z.-B.Han, "Chromosome extraction based on U-Net and YOLOv3," IEEE Access, vol.8, pp.178563-178569, 2020.) for performance comparison, the training methods used were the same, and the results are shown in Table 6; and the accuracy of the karyotype chromosome automatic detection and recognition method and system based on deep learning disclosed in the present invention and DeepACEV2 in identifying difficult images is compared, and the results are shown in Table 7. Among them, DeepACEV2 regards overlapping chromosomes as difficult images, finds overlapping chromosomes based on the IOU of objects and calculates their accuracy, while the difficult images defined by the present invention adopt the standards of clinical medical examiners, so compared with DeepACEV2, the difficulty of the difficult images judged by the present invention is higher.
由表6及表7之結果可知,本發明之準確度上係較deepACEv2高0.07%,且在測試資料量上是DeepACv2的3倍以上,且圖像更加困難的情況下,本發明依然能獲得98.78的高準確度。由此結果證明了本發明所揭基於深度學習之核型圖染色體自動偵測辨識方法及系統具有極佳之穩定性及穩健性。 From the results in Table 6 and Table 7, it can be seen that the accuracy of the present invention is 0.07% higher than that of deepACEv2, and the amount of test data is more than 3 times that of DeepACv2. In the case of more difficult images, the present invention can still obtain a high accuracy of 98.78. This result proves that the method and system for automatic detection and identification of karyotype chromosomes based on deep learning disclosed in the present invention has excellent stability and robustness.
圖1係為總數據量(張數)和準確率(%)之曲線圖。 Figure 1 is a graph showing the total data volume (number of images) and accuracy (%).
圖2係為epoch(訓練次數)和準確率(%)之曲線圖。 Figure 2 is a graph showing epoch (number of training times) and accuracy (%).
圖3係為簡單之染色體圖樣。 Figure 3 is a simple chromosome diagram.
圖4係為困難之染色體圖樣。 Figure 4 is a difficult chromosome diagram.
圖5係為高度困難之染色體圖樣。 Figure 5 is a highly difficult chromosome pattern.
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