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研究生: 賴柏毓
Lai, Po-Yu
論文名稱: 用於果蠅神經元編碼之類樂高積木的演算法實作與早期評估
Implementation and early evaluation of an algorithm for encoding Drosophila neurons like lego bricks
指導教授: 吳馬丁
Torbjörn E. M. Nordling
學位類別: 碩士
Master
系所名稱: 工學院 - 機械工程學系
Department of Mechanical Engineering
論文出版年: 2020
畢業學年度: 108
語文別: 英文
論文頁數: 49
中文關鍵詞: 神經相似度連接組集群分析序列對比資料轉換模組化
外文關鍵詞: neural similarity, connectome, clustering analysis, sequence alignment, data conversion, modularity
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  • 背景:
    為了了解我們的大腦運作方式,科學家們試圖繪製出所有神經元之間的聯繫,即所謂的連接組。由於成像技術的局限性,即使是果蠅大腦也無法一次成像所有的神經元。因此,需要透過許多局部圖像將整體連接體拼湊在一起,比較和識別單個神經元是不可少的。果蠅神經元圖像的比較是一項艱鉅的工作。目前最好的方法-神經局部比對搜索工具(NBLAST)繁重的前處理會影響結果精準與否。更確切地說,NBLAST要求將每個神經圖像變形為標準模型大小來進行對比。
    目標:
    本論文主旨在實現和評估一種用於將神經圖像自動處理為一系列標準單位以便於比較神經元的演算法。此演算法的基本概念是由台灣國家高速網路與計算中心(NCHC)的陳南佑博士所發明的。
    方法:
    我們的演算法從提取神經元每個分支點的幾個無因次特徵開始。通過對這些分支點的特徵進行集群分析,我們將有限的標籤重新分配給每個分支點,重此以後定義為“神經樂高”。將神經樂高的樹狀結構轉換為序列後,可以通過序列比對來比較兩個神經元。
    結果與結論:
    於此論文中以C/C++程式實現了該算法,並針對過程的一部分探索了幾種替代解決方案。我們發現了用於圖論的模組化方法和分層聚類在一些情況下可產生相似結果,也發現在模組化中使用多分辨率可以提供一種更好的合併群集的方法。我們發現從原始圖像中自動提取的神經元包含雜訊,這使得很難確定聚類結果是否良好,因此需要進一步改進。我們注意到在將帶有標籤的樹狀資料用我們的方法轉換為序列的過程中遺失了些資訊。 沒有足夠的數據來構建統計上有效的序列比對評分系統。對於上述的問題中,有許多替代方法可以解決上述問題。因此,對神經樂高的算法是否有用下結論還為時過早。我們對結果進行一些解釋,並列出一些未來的建議。

    Background:
    As a part of the scientific endeavor to understand how our brain works, scientists are trying to map out the connections between all neurons—the so called connectome. Due to limitations in the imaging techniques, it is not yet possible to image all neurons at once even for the fruit fly brain. Therefore the connectome need to be pieced together based on many images and it is essential to compare and recognize individual neurons. Comparison of images of Drosophila melanogaster neurons is a laborious job. The state of the art method—Neural Basic Local Alignment Search Tool (NBLAST)—depend on heavy preprocessing before the comparison. More precisely, NBLAST requires warping of each neural image into a standard model size.
    Aim:
    This thesis aims to implement and evaluate an algorithm for automated processing of neural images into a sequence of standard elements for easy comparison of neurons. The basic algorithm was invented by Dr. Nan ­Yow Chen at the National Center for High-Performance Computing (NCHC) in Taiwan.
    Method:
    Our algorithm starts with the extraction of several dimensionless features of each branch point of a neuron. By clustering the branch points based on these features, we assign a label from a finite vocabulary to each branch point, henceforth called ``Neural Lego'. This enables comparison of two neurons through sequence alignment after the tree of labels is converted into a sequence.
    Results and conclusion:
    We implemented the algorithm in functional C/C++ code and explored several alternative solutions for parts of the process. We discovered some cases where modularity and hierarchical clustering yields a similar result. We discovered that the use of multiresolution in modularity can provide a better way of merging clusters. We found that the automatically extracted neurons from the raw images contain noise, which make it difficult to determine whether the clustering result is good or not and thus requires further improvement. We showed that information is lost during the conversion of the tree of labels into a sequence. We did not have enough data to construct a statistical sequence alignment scoring system. There are many alternative ways to solve the mentioned problems. Thus, it is still too early to conclude if our Neural Lego based algorithm can work or not. We provide some interpretation of our results and list some future suggestions.

    Chinese abstract i Abstract iii Acknowledgment v Table of Contents vi List of Tables viii List of Figures ix List of Symbols ix 1 Introduction 1 1.1 Motivation and objective . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2 Delimitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 Introduction to connectome . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.4 Introduction to neuron similarity . . . . . . . . . . . . . . . . . . . . . . . 7 1.5 Introduction to cluster analysis . . . . . . . . . . . . . . . . . . . . . . . . 8 1.6 Introduction to modularity . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1.7 Introduction to sequence alignment . . . . . . . . . . . . . . . . . . . . . . 12 1.8 Organization of this thesis . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2 Theory and Method 14 2.1 Information extraction and graph transformation . . . . . . . . . . . . . . . 14 2.2 Modularity-community detection . . . . . . . . . . . . . . . . . . . . . . . 18 2.3 Sequence alignment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.3.1 Global and local alignment . . . . . . . . . . . . . . . . . . . . . . 22 2.3.2 Scoring matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3 Results and Discussion 24 3.1 Results and problems in extraction . . . . . . . . . . . . . . . . . . . . . . 24 3.2 Problem with modularity . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.3 Sequence alignment and conversion . . . . . . . . . . . . . . . . . . . . . 43 4 Conclusion and Future works 44 4.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 4.2 Future works . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 References 46

    Aimon, S. and Grunwald Kadow, I. C. (2020). Studying complex brain dynamics using
    drosophila. Journal of Neurogenetics, 34(1):171–177.
    Altschul, S. F., Gish, W., Miller, W., Myers, E. W., and Lipman, D. J. (1990). Basic local
    alignment search tool. Journal of molecular biology, 215(3):403–410.
    Anderberg, M. R. (2014). Cluster analysis for applications: probability and mathematical
    statistics: a series of monographs and textbooks, volume 19. Academic press.
    Azevedo, F. A., Carvalho, L. R., Grinberg, L. T., Farfel, J. M., Ferretti, R. E., Leite, R. E.,
    Filho, W. J., Lent, R., and Herculano-Houzel, S. (2009). Equal numbers of neuronal and
    nonneuronal cells make the human brain an isometrically scaled-up primate brain. Journal
    of Comparative Neurology, 513(5):532–541.
    Bargmann, C. I. and Marder, E. (2013). From the connectome to brain function. Nature
    methods, 10(6):483.
    Basu, S., Condron, B., and Acton, S. T. (2011). Path2path: Hierarchical path-based analysis
    for neuron matching. In 2011 IEEE International Symposium on Biomedical Imaging:
    From Nano to Macro, pages 996–999. IEEE.
    Berkhin, P. (2006). A survey of clustering data mining techniques. In Grouping multidimensional
    data, pages 25–71. Springer.
    Blondel, V. D., Guillaume, J.-L., Lambiotte, R., and Lefebvre, E. (2008). Fast unfolding of
    communities in large networks. Journal of statistical mechanics: theory and experiment,
    2008(10):P10008.
    Bock, D. D., Lee, W.-C. A., Kerlin, A. M., Andermann, M. L., Hood, G., Wetzel, A. W.,
    Yurgenson, S., Soucy, E. R., Kim, H. S., and Reid, R. C. (2011). Network anatomy and in
    vivo physiology of visual cortical neurons. Nature, 471(7337):177–182.
    Briggman, K. L., Helmstaedter, M., and Denk, W. (2011). Wiring specificity in the directionselectivity
    circuit of the retina. Nature, 471(7337):183–188.
    Cardona, A., Saalfeld, S., Arganda, I., Pereanu, W., Schindelin, J., and Hartenstein, V. (2010).
    Identifying neuronal lineages of drosophila by sequence analysis of axon tracts. Journal
    of Neuroscience, 30(22):7538–7553.
    Costa, M., Manton, J. D., Ostrovsky, A. D., Prohaska, S., and Jefferis, G. S. (2016).
    Nblast: rapid, sensitive comparison of neuronal structure and construction of neuron family
    databases. Neuron, 91(2):293–311.
    Dayhoff, M., Schwartz, R., and Orcutt, B. (1978). 22 a model of evolutionary change in
    proteins. Atlas of protein sequence and structure, 5:345–352.
    Fortunato, S. (2010). Community detection in graphs. Physics reports, 486(3-5):75–174.
    Fortunato, S. and Barthelemy, M. (2007). Resolution limit in community detection. Proceedings
    of the national academy of sciences, 104(1):36–41.
    Girvan, M. and Newman, M. E. (2002). Community structure in social and biological networks.
    Proceedings of the national academy of sciences, 99(12):7821–7826.
    Gollery, M. (2005). Bioinformatics: Sequence and genome analysis, david w. mount. cold
    spring harbor, ny: Cold spring harbor laboratory press, 2004, 692 isbn 0-87969-712-1.
    Clinical Chemistry, 51(11):2219–2219.
    Green, J., Adachi, A., Shah, K. K., Hirokawa, J. D., Magani, P. S., and Maimon, G. (2017).
    A neural circuit architecture for angular integration in drosophila. Nature, 546(7656):
    101–106.
    Guimera, R., Sales-Pardo, M., and Amaral, L. A. N. (2004). Modularity from fluctuations in
    random graphs and complex networks. Physical Review E, 70(2):025101.
    Hagmann, P., Cammoun, L., Gigandet, X., Meuli, R., Honey, C. J., Wedeen, V. J., and Sporns,
    O. (2008). Mapping the structural core of human cerebral cortex. PLoS Biol, 6(7):e159.
    Henikoff, S. and Henikoff, J. G. (1992). Amino acid substitution matrices from protein
    blocks. Proceedings of the National Academy of Sciences, 89(22):10915–10919.
    Jain, A. K. (2010). Data clustering: 50 years beyond k-means. Pattern recognition letters,
    31(8):651–666.
    Jain, A. K., Murty, M. N., and Flynn, P. J. (1999). Data clustering: a review. ACM computing
    surveys (CSUR), 31(3):264–323.
    Johnson, L. S., Eddy, S. R., and Portugaly, E. (2010). Hidden markov model speed heuristic
    and iterative hmm search procedure. BMC bioinformatics, 11(1):431.
    Johnson, S. C. (1967). Hierarchical clustering schemes. Psychometrika, 32(3):241–254.
    Kadow, I. C. G. (2019). State-dependent plasticity of innate behavior in fruit flies. Current
    Opinion in Neurobiology, 54:60–65.
    Kim, S. M., Su, C.-Y., and Wang, J. W. (2017). Neuromodulation of innate behaviors in
    drosophila. Annual Review of Neuroscience, 40.
    Kohatsu, S. and Yamamoto, D. (2015). Visually induced initiation of drosophila innate
    courtship-like following pursuit is mediated by central excitatory state. Nature communications,
    6(1):1–9.
    MacQueen, J. et al. (1967). Some methods for classification and analysis of multivariate
    observations. In Proceedings of the fifth Berkeley symposium on mathematical statistics
    and probability, volume 1, pages 281–297. Oakland, CA, USA.
    Mann, K., Gallen, C. L., and Clandinin, T. R. (2017). Whole-brain calcium imaging reveals
    an intrinsic functional network in drosophila. Current Biology, 27(15):2389–2396.
    Mayerich, D., Bjornsson, C., Taylor, J., and Roysam, B. (2012). Netmets: software for quantifying
    and visualizing errors in biological network segmentation. BMC bioinformatics,
    13(8):S7.
    Mountcastle, V. B. (1997). The columnar organization of the neocortex. Brain: a journal of
    neurology, 120(4):701–722.
    Murre, J. M. and Sturdy, D. P. (1995). The connectivity of the brain: multi-level quantitative
    analysis. Biological cybernetics, 73(6):529–545.
    Nässel, D. R. (2002). Neuropeptides in the nervous system of drosophila and other insects:
    multiple roles as neuromodulators and neurohormones. Progress in neurobiology, 68(1):
    1–84.
    Newman, M. E. (2006). Modularity and community structure in networks. Proceedings of
    the national academy of sciences, 103(23):8577–8582.
    Pearson, W. R. (1991). Searching protein sequence libraries: comparison of the sensitivity
    and selectivity of the smith-waterman and fasta algorithms. Genomics, 11(3):635–650.
    Polyanovsky, V. O., Roytberg, M. A., and Tumanyan, V. G. (2011). Comparative analysis
    of the quality of a global algorithm and a local algorithm for alignment of two sequences.
    Algorithms for molecular biology, 6(1):25.
    Seung, S. (2012). Connectome: How the Brain’s Wiring Makes Us Who We Are. Houghton
    Mifflin Harcourt Trade, none edition.
    Shrivastava, P. and Gupta, H. (2012). A review of density-based clustering in spatial data.
    International Journal of Advanced Computer Research, 2(3):200.
    Smith, T. F., Waterman, M. S., et al. (1981). Identification of common molecular subsequences.
    Journal of molecular biology, 147(1):195–197.
    Sporns, O., Tononi, G., and Kötter, R. (2005). The human connectome: a structural description
    of the human brain. PLoS Comput Biol, 1(4):e42.
    Spr, C. (1970). A general method applicable to the search for similarities in the amino acid
    sequence of two proteins. Mol. Biol, 48:443–153.
    Wan, Y., Long, F., Qu, L., Xiao, H., Hawrylycz, M., Myers, E. W., and Peng, H. (2015).
    Blastneuron for automated comparison, retrieval and clustering of 3d neuron morphologies.
    Neuroinformatics, 13(4):487–499.
    Weiss, R. S. and Jacobson, E. (1955). A method for the analysis of the structure of complex
    organizations. American Sociological Review, 20(6):661–668.
    White, J. G., Southgate, E., Thomson, J. N., and Brenner, S. (1986). The structure of the
    nervous system of the nematode caenorhabditis elegans. Philos Trans R Soc Lond B Biol
    Sci, 314(1165):1–340.
    Yoshimura, Y., Dantzker, J. L., and Callaway, E. M. (2005). Excitatory cortical neurons form
    fine-scale functional networks. Nature, 433(7028):868–873.

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