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研究生: 陳姵蓁
Chen, Pei-Chen
論文名稱: 用於自動讀取微陣列之多頭深度學習模型
A Multi-Head Deep Learning Model for Automatic Microarray Readout
指導教授: 張天豪
Chang, Tien-Hao
共同指導教授: 陳健生
Chen, Chien-Sheng
許觀達
Syu, Guan-Da
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 50
中文關鍵詞: 微陣列晶片強度讀取模型多頭深度學習模型
外文關鍵詞: microarray, automatic readout, multi-head deep learning model
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  • 微陣列晶片是一種用來進行快速且大量生物檢測的工具,上頭有數千至數萬個如陣列般排列整齊的生物探針,會和檢測樣本中的待測物進行高度專一性的反應。其分析的第一步是使用微陣列晶片掃描機將微陣列晶片掃描成圖檔,圖片上的一個點代表一個生物探針,接著第二步是定位出圖上每個點的座標位置,得到各點的位置資訊後,第三步是算出每個點的強度讀值,此讀值代表的是生物探針與待測物的結合狀況,最後第四步就可以用各點的強度讀值做後續的數據分析。
    近年來深度學習蓬勃發展,許多領域都嘗試以深度學習來實現自動化,在微陣列晶片的分析上,也陸續有研究提出基於深度學習的自動對點演算法以及自動強度讀取演算法,用來使微陣列晶片的分析流程更加自動化。本研究觀察過去的自動強度讀取演算法,發現三個會導致模型的讀值預測不準確的問題。為此,本研究以過去的自動強度讀取演算法的架構為基礎,並加以改進,提出了一個基於多頭深度學習的自動強度讀取演算法。
    實驗結果顯示本研究提出的改進方法對於微陣列晶片的讀值預測有顯著的幫助。在數據分析階段,過去的自動強度讀取演算法所輸出的讀值,在新冠肺炎資料集上疾病檢測的AUC 只能達到 0.916,而本研究提出的自動強度讀取演算法所輸出的讀值,在同一個資料集的疾病檢測 AUC 可以達到 0.957。本研究提出之自動讀值演算法搭配自動對點演算法,可以達到完全自動化的分析。

    Microarray chip is a tool for rapid and large-scale biological detection. There are thousands of biological probes arranged neatly like an array on the chip. The biological probes would have a highly specific reaction with the analyte in the testing samples. To analyze the microarray, the first step is to use the microarray scanner to scan the chip into an image file. Every spot on the image represents a biological probe. The second step is to locate the coordinate of each spot on the image. Subsequently, the third step is to calculate the intensity reading of each spot, which reflects the binding state of biological probes and the analytes. Finally, the fourth step is to use the intensity reading of each spot to do the follow-up data analysis.
    In recent years, deep learning has been applied to many fields to fulfill automatic systems. For the microarray analysis, there are some studies based on deep learning are proposed to achieve automatic gridding and automatic intensity reading. However, there are some problems existing in previous automatic intensity reading algorithms being observed. Referring to the structure of previous automatic intensity reading algorithms, this work proposes an automatic intensity reading algorithm based on multi-head deep learning that try to solve the problems leading to inaccurate readout predictions.
    The experimental results show that the method proposed in this study are all significantly helpful for the prediction of microarray readouts. In the data analysis stage, the readouts predicted by the previous automatic intensity reading algorithm can only reach 0.916 in the AUC of disease detection in the COVID-19 microarray dataset, while the improved automatic intensity reading algorithm proposed in this research could reach up to 0.957. The automatic intensity reading algorithm proposed in this study can combined with the automatic gridding algorithm to achieve fully automatic analysis for microarray.

    第一章 緒論 1 第二章 相關研究 5 2.1 微陣列晶片 5 2.2 影像優化技術 8 2.3 類神經網路 9 2.3.1 卷積神經網路 (Convolutional Neural Network, CNN) 10 2.3.2 殘差網路 (Residual Network, ResNet) 12 2.4 微陣列晶片數值分析 13 2.4.1 傳統讀值方法 13 2.4.2 全自動化讀值方法 15 第三章 研究方法 18 3.1資料集 18 3.1.1 新冠肺炎微陣列晶片 18 3.2 影像前處理 20 3.2.1 影像擷取 20 3.2.2 影像增強 21 3.3 自動讀值模型 22 3.3.1 迴歸任務 22 3.3.2 二元分類任務 24 3.3.3 多頭深度學習模型 [結合迴歸任務和二元分類任務] 25 第四章 研究結果 27 4.1 效能評估方式 27 4.1.1 標準答案定義 27 4.1.2 效能評估指標 28 4.2 實驗設置 29 4.3 和其他讀值模型效能比較 30 4.4 使用影像增強的影響 32 4.5 改進回歸頭之損失函數的影響 34 4.6 使用多頭模型的影響 37 第五章 討論 39 5.1 ReadNet_v2 搭配不同對點方式的效果 39 5.2 自動讀值模型在生物標記前五名的個別效能比較 39 5.3 自動讀值模型在不同門檻值的效能比較 41 5.4 自動讀值模型使用不同資料集驗證的效能 42 5.5 自動讀值模型使用不同數量的訓練資料的效能比較 45 第六章 結論 46 6.1 結論 46 6.2 未來展望 46 第七章 引用項目 47

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