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生物資訊 ( Bioinformatics )

生物資訊 ( Bioinformatics ). 蔡懷寬 E-mail: d7526010@csie.ntu.edu.tw. Please tell me. Why you are here? Make a definition of bioinformatics. Introduction. What is bioinformatics? Why bioinformatics? The past, current, and future in bioinformatics. 什麼是生物資訊學？. 它是一個跨領域的學門： 結合生物、資訊科學、數學、物理及化學等領域

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生物資訊 ( Bioinformatics )

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  1. 生物資訊(Bioinformatics) 蔡懷寬 E-mail: d7526010@csie.ntu.edu.tw

  2. Please tell me • Why you are here? • Make a definition of bioinformatics

  3. Introduction • What is bioinformatics? • Why bioinformatics? • The past, current, and future in bioinformatics

  4. 什麼是生物資訊學？ • 它是一個跨領域的學門： • 結合生物、資訊科學、數學、物理及化學等領域 • 終極目標：了解生物特性及生命本質 • 重要的子領域： • 大量資料的分析演算法及統計方法 • 各種生物序列, 結構, 功能及演化的分析與解釋 • 管理及使用各種型態資訊的軟體工具

  5. 為什麼需要生物資訊學？

  6. HIGH-THROUGHPUT APPROACH CLASSICAL APPROACH EXPERIMENT DRIVEN Hypothesis Experiment INFORMATION DRIVEN Experiment  Hypothesis REVOLUTION IN BIO-MEDICAL RESEARCH Northern Hybridization Western Hybridization Southern Hybridization RFPD Differential Display Subtraction Library Real-Time PCR Microarray 2-Dimensional Protein Electrophoresis Serial Analysis of Gene Expression Expression Sequence Tags

  7. 為什麼需要生物資訊學？ • 生物相關資料的累積迅速，資料量非常大，亟需電腦協助分析

  8. The GeneBank Data (9/25/2002)

  9. Protein DataBank Data (9/25/2002)

  10. 為什麼需要生物資訊學？ • 生物相關資料的累積迅速，資料量非常大，亟需電腦協助分析 • 提供實驗設計更宏觀的看法，從以往個別基因的研究，邁向整個基因組的研究 • 透過資料挖掘來了解基因功能及蛋白質結構 • 更進一步了解演化歷史及物種間的演化關係

  11. 人類基因組解讀計畫

  12. 基因組(genome) • All the genetic material in the chromosomes of a particular organism • Its size is generally given as its total number of base pairs.

  13. 基因組的大小 • Human: 3000 million bases • Mouse: 3000 million bases • Drosophila (fruit fly): 165 million bases • Nematode (roundworm): 100 million bases • Yeast (fungus): 14 million bases • E. coli (bacteria) 4.67 million bases

  14. 人類基因組解讀計畫 • 簡稱為HGP (Human Genome Project) • 主要目標有： • identify all the genes in human DNA, • determine the sequences of the 3 billion chemical bases that make up human DNA • store this information in databases • develop tools for data analysis • transfer related technologies to the private sector • address the ethical, legal, and social issues (ELSI) that may arise from the project

  15. Human Genome

  16. HGP的沿革與進展 • HGP從1990年起開始進行 • HGP是由美國及英國所主導的一項全球性計畫 • 2000年六月與Celera私人公司共同宣布人類基因組的初稿已完成

  17. HGP的沿革與進展(續) • 2001年2月: • Initial sequencing and analysis of the human genome (Nature, Vol. 409, 15 Feb. 2001, by International Human Genome Sequencing Consortium) • The sequence of the human genome (Science, Vol. 291, 16 Feb. 2001, by J. C. Venter, et al.)

  18. Biology moves into the silicon stage in vivo in vitro in silico

  19. 從HGP來看整個生物資訊界的脈動

  20. Before HGP • String analysis • Pair-wise, multiple sequence alignment

  21. Sequence Analysis Alignment • Pair-wise alignment SURVIVE SURVIVE SURIUE SUR- IUE • Multiple sequence alignment RPCVCPVLRQAAQ s1 RPCVC_ P__VLRQAAQ a1 RPCACCPVLRQVVQ s2 RPCACCP__VLRQVVQ a2 KPCLCPRQLRQV s3 KPCLC_ P RQLRQV_ _ a3 KPCCPRQAAQ s4 KPC_C_ P____ RQAAQ a4 S A

  22. Before HGP • String alignment • Pair-wise, multiple alignment • Linkage analysis

  23. Linkage Analysis

  24. Before HGP • String alignment • Pair-wise, multiple alignment • Linkage analysis • Phylogenetic tree

  25. Phylogenetic Tree

  26. Phylogenetic Tree

  27. Before HGP • String alignment • Pair-wise, multiple alignment • Linkage analysis • Phylogenetic tree • Protein structure prediction • …

  28. Protein Structure Prediction

  29. During HGP • Sequencing • Physical mapping • Fragment assembly

  30. Sequencing Strategies (1) • Map-Based Assembly: • Create a detailed complete fragment map • Time-consuming and expensive • Provides scaffold for assembly • Original strategy of Human Genome Project

  31. Sequencing Strategies (2) • Shotgun: • Quick, highly redundant – requires 7-9X coverage for sequencing reads of 500-750bp. This means that for the Human Genome of 3 billion bp, 21-27 billion bases need to be sequence to provide adequate fragment overlap. • Computationally intensive • Troubles with repetitive DNA • Original strategy of Celera Genomics

  32. Shotgun Sequencing: Assembly of Random Sequence Fragments • To sequence a Bacterial Artificial Chromosome (100-300Kb), millions of copies are sheared randomly, inserted into plasmids, and then sequenced. If enough fragments are sequenced, it will be possible to reconstruct the BAC based on overlapping fragments.

  33. During HGP • Sequencing • Physical mapping • Fragment assembly • Gene Prediction

  34. During HGP • Sequencing • Physical mapping • Fragment assembly • Gene Prediction • …

  35. After HGP (Post Genomic) • Microarray

  36. Microarray

  37. After HGP (Post Genomic) • Microarray • Regulatory network

  38. Regulatory Network  Simplified representation of the NF- B network.

  39. After HGP (Post Genomic) • Microarray • Regulatory network • Proteomics • …

  40. 生物資訊學的相關課題

  41. 生物資訊相關主題(1) • 定序(sequencing) • 基因組的DNA序列很長，但卻扭曲在小小的細胞內，目前仍然沒有方法可以一次將整個序列讀出來 • 現階段的方法都是將基因組序列切成很多的小段，然後藉由重疊的區域將整個基因組序列再組合回來

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