簡易檢索 / 詳目顯示

研究生: 王任權
Wang, Ren-Chiuan
論文名稱: 預測果蠅腦神經元連接的評估方法
Evaluating Methods for Predicting Neuronal Connections in the Drosophila Brain
指導教授: 羅中泉
Lo, Chung-Chun
口試委員: 施奇廷
shih, chi-ting
朱麗安
chu, li-an
學位類別: 碩士
Master
系所名稱: 生命科學暨醫學院 - 系統神經科學研究所
Institute of Systems Neuroscience
論文出版年: 2020
畢業學年度: 109
語文別: 中文
論文頁數: 43
中文關鍵詞: 果蠅連結接觸點極性骨架中央複合體
外文關鍵詞: Drosophila, connection, contaact point, polarity, skeleton, central complex
相關次數: 點閱:2下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 果蠅的大腦包含超過100000個神經元。過去以螢光成像描繪果蠅神經元的型態,然而這樣的成像方法大多只能一次取得一顆或少數幾顆神經元,因此要更進一步的了解果蠅大腦連結體,預測這些神經元之間的連接是一項至關重要但具有挑戰性的任務。先前的研究已經開發了幾種基於距離和接觸點作為標準來估計神經元連接的方法。第一個參數是兩個神經元之間的最短距離閾值,當兩神經元的距離小於最短距離閾值後可以將其視為接觸。第二個參數是接觸點數目的比例,我們計算兩個神經元之間有多少個接觸點的距離小於最短距離閾值。此外,我們考慮端點和分支的差異,分析以端點或分支之間的距離來預測時,何者有較好的表現。
    本研究將以過去在中央複合體上的實驗數據作為標準答案,進行統計分析來確定最佳預測方法和標準。我們發現,以線段到線段的距離評估時,在10um可得精度最高,而最佳接觸點比例標準是1%,另外我們也加入神經極性的參數,特別只考慮經典的軸突到樹突的連結時,可以有更好的表現。跟以往的方法相比,我們將準確率從80%提升到91%,誤報率從5.7%降至2.5%。未來我們將在應用我們的方法到整個果蠅大腦的數據,以生成果蠅大腦的高精度連接體。


    A Drosophila brain encompasses more than 100000 neurons. To delineate the connections between these neurons in a fluorescent-image-based database is a crucial but challenging task. Previous studies have developed several approaches to estimate neuronal connections based on the distance and contact point criteria. The distance criterion indicates the shortest distance between two neurons that can be considered as making a contact while the contact point criterion sets the minimum value of the contact points between two neurons that are determined to form synaptic connections. Moreover, the distance can be calculated based on the distance between terminal points or branch segments. The goal of this project is to determine the best method and the optimal criteria by performing statistical analyses based on the ground truth data, which were compiled based on previously published papers on the central complex. We found that the highest accuracy was yield from the method based on the segment to segment at distance is 10um , the best contact point criteria was 1 percent, the shortest distance occurs between axon and dendrite. We increased the TPR from 80 percent to 91percent, and decreased FPR from 5.7 percent to 2.5 percent. We will apply our method on the FlyCircuit database to generate a highly accurate connectome of the fruit fly brain.

    中文摘要 i Abstract ii 誌謝 iii 第一章 1 1.簡介 1 第二章材料和方法 3 2.1 Ground truth data 3 2.2數據預處理與分析 4 2.3突觸極性預測和驗證 4 2.4突觸權重預測和連接驗證 5 2.4.1整體距離與幾種計算方法 5 2.4.2 接觸點(contact point) 7 2.4.2.1 總接觸點數 7 2.4.2.2 總接觸點數比率 7 2.4.2.3 軸突接觸點數比率 8 2.4.2.4 樹突接觸點數比率 8 2.4.2.5 軸突接觸點數比率+每個有接觸的軸突與總接觸點數比率 8 2.4.3 接觸點角度 9 2.4.3.1 父節點向量(parent node vector)對接觸父節點向量(contact parent node vector)角度 9 2.4.3.2 分支點向量(branch node vector)對接觸分支點向量(contact branch node vector)角度 9 2.4.3.3 父節點向量對接觸分支點向量角度 10 2.4.3.4 分支點向量對接觸父節點向量角度 10 2.4.3.5 父節點向量對接觸點向量角度 10 2.4.4 特定距離下軸突接觸點比率提升程度 10 2.4.5 軸突接觸點比率+最小距離 11 2.4.6 各別軸突節點接觸點比率 11 2.4.7以往的判斷連結的方法 11 2.5 ROC curve ( Receiver operating characteristic curve) 13 第三章結果與分析 16 3.1 整體距離與幾種計算方法(節點) 16 3.2 接觸點(節點) (contact point) 17 3.2.1 總接觸點數 17 3.2.2 總接觸點數比率 18 3.2.3 軸突接觸點數比率 19 3.2.4樹突接觸點數比率 20 3.2.5軸突接觸點數比率+每個軸突接觸點的接觸點平均 21 3.3 接觸點角度 23 3.3.1 父節點對接觸父節點角度 23 3.3.2分支點對接觸分支點角度 24 3.3.3 父節點對接觸分支點角度 25 3.3.4 分支點對接觸父節點角度 26 3.3.5 父節點對接觸點角度 27 3.4 各別距離下axon接觸點比率提升程度 28 3.5 最小距離 29 3.6軸突接觸點數比率+最小距離(segment) 32 3.8最佳評估閾值 35 3.9 Ring neuron測試 36 3.10與以往的方法比較 36 第四章討論 38 4.1結論 38 第五章參考文獻 40

    1. Seung, S. (2012). Connectome: How the brain's wiring makes us who we are. HMH.
    2. Peters, A. (1979). Thalamic input to the cerebral cortex. Trends in Neurosciences, 2, 183-185.
    3. Binzegger, T., Douglas, R. J., & Martin, K. A. (2004). A quantitative map of the circuit of cat primary visual cortex. Journal of Neuroscience, 24(39), 8441-8453.
    4. Van Pelt, J., Carnell, A., De Ridder, S., Mansvelder, H. D., & Van Ooyen, A. (2010). An algorithm for finding candidate synaptic sites in computer generated networks of neurons with realistic morphologies. Frontiers in Computational Neuroscience, 4, 148.
    5. Morgan, J. L., & Lichtman, J. W. (2013). Why not connectomics?. Nature methods, 10(6), 494.
    6. Huang, Y. C., Wang, C. T., Su, T. S., Kao, K. W., Lin, Y. J., Chuang, C. C., ... & Lo, C. C. (2019). A single-cell level and connectome-derived computational model of the Drosophila brain. Frontiers in neuroinformatics, 12, 99.
    7. Lin, C. Y., Chuang, C. C., Hua, T. E., Chen, C. C., Dickson, B. J., Greenspan, R. J., & Chiang, A. S. (2013). A comprehensive wiring diagram of the protocerebral bridge for visual information processing in the Drosophila brain. Cell reports, 3(5), 1739-1753.
    8. Craig, A. M., & Banker, G. (1994). Neuronal polarity. Annual review of neuroscience, 17, 267-310.
    9. Lee, Y. H., Lin, Y. N., Chuang, C. C., & Lo, C. C. (2014). SPIN: a method of skeleton-based polarity identification for neurons. Neuroinformatics, 12(3), 487-507.
    10. Peters, A., & Payne, B. R. (1993). Numerical relationships between geniculocortical afferents and pyramidal cell modules in cat primary visual cortex. Cerebral Cortex, 3(1), 69-78.
    11. Douglass, J. K., & Strausfeld, N. J. (2003). Anatomical organization of retinotopic motion‐sensitive pathways in the optic lobes of flies. Microscopy research and technique, 62(2), 132-150.
    12. Tanaka, N. K., Endo, K., & Ito, K. (2012). Organization of antennal lobe‐associated neurons in adult Drosophila melanogaster brain. Journal of Comparative Neurology, 520(18), 4067-4130.
    13. Fawcett, T. (2006). An introduction to ROC analysis. Pattern recognition letters, 27(8), 861-874.
    14. Clements, J., Dolafi, T., Umayam, L., Neubarth, N. L., Berg, S., Scheffer, L. K., & Plaza, S. M. (2020). neuprint: Analysis tools for em connectomics. BioRxiv.
    15. Chiang, A. S., Lin, C. Y., Chuang, C. C., Chang, H. M., Hsieh, C. H., Yeh, C. W., ... & Wu, C. C. (2011). Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution. Current biology, 21(1), 1-11.
    16. Abbott, L. F., Varela, J. A., Sen, K., & Nelson, S. B. (1997). Synaptic depression and cortical gain control. Science, 275(5297), 221-224.
    17. Chang, P. Y., Su, T. S., Shih, C. T., & Lo, C. C. (2017). The topographical mapping in Drosophila central complex network and its signal routing. Frontiers in neuroinformatics, 11, 26
    18. Li, W. C., Cooke, T., Sautois, B., Soffe, S. R., Borisyuk, R., & Roberts, A. (2007). Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network. Neural Development, 2(1), 17.
    19. van Pelt, J., & van Ooyen, A. (2013). Estimating neuronal connectivity from axonal and dendritic density fields. Frontiers in computational neuroscience, 7, 160.
    20. Lo, C. C., & Chiang, A. S. (2016). Toward whole-body connectomics. Journal of Neuroscience, 36(45), 11375-11383.
    21. Rolls, M. M. (2011). Neuronal polarity in Drosophila: sorting out axons and dendrites. Developmental neurobiology, 71(6), 419-429.
    22. Rolls, M. M., Satoh, D., Clyne, P. J., Henner, A. L., Uemura, T., & Doe, C. Q. (2007). Polarity and intracellular compartmentalization of Drosophila neurons. Neural development, 2(1), 7.
    23. Shinomiya, K., Matsuda, K., Oishi, T., Otsuna, H., & Ito, K. (2011). Flybrain neuron database: a comprehensive database system of the Drosophila brain neurons. Journal of Comparative Neurology, 519(5), 807-833.
    24. S Sporns, O. (2013). Making sense of brain network data. Nature methods, 10(6), 491-493.
    25. Hellwig, B. (2000). A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex. Biological cybernetics, 82(2), 111-121.
    26. Feldmeyer, D., Lübke, J., Silver, R. A., & Sakmann, B. (2002). Synaptic connections between layer 4 spiny neurone‐layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. The Journal of physiology, 538(3), 803-822.
    27. Ascoli, G. A. (2006). Mobilizing the base of neuroscience data: the case of neuronal morphologies. Nature Reviews Neuroscience, 7(4), 318-324.
    28. Scheffer, L. K., Xu, C. S., Januszewski, M., Lu, Z., Takemura, S. Y., Hayworth, K. J., ... & Clements, J. (2020). A Connectome and Analysis of the Adult Drosophila Central Brain. BioRxiv.
    29. FlyBase Consortium. (2003). The FlyBase database of the Drosophila genome projects and community literature. Nucleic acids research, 31(1), 172-175.
    30. Buhmann, J., Sheridan, A., Gerhard, S., Krause, R., Nguyen, T., Heinrich, L., ... & Jefferis, G. S. (2019). Automatic Detection of Synaptic Partners in a Whole-Brain Drosophila EM Dataset. bioRxiv.

    QR CODE