分子生物学的本质仍是描述性的科学.pdf

YM Bioinfo Biological pathways Ueng Cheng Yang June 3 2005 YM Bioinfo 分子生物學的本質仍是描述性的科學 Picture modified from http esg www mit edu 8001 esgbio 分子 解剖 學分子 生物 學 YM Bioinfo Technology advancement may create a breakthrough in biology Discovering DNA structure Genetic engineering Genome projects Integration of math physics chemistry informatics etc 1953 1973 1990 Conceptual model Technology advancement Concept change YM Bioinfo The dream of molecular biologists Cell 100 1 57 70 Review 2000 PNAS Vol 95 14863 14868 Science Vol 292 May 2001 YM Bioinfo Pathway database is the basis for computer inference and computational biology Making observation Propose hypothesis Testing hypothesis Knowledge Information integration ELU centrifugal elutriation 14 CDC15 cdc15 ts 15 SPO sporulation 7 HT shock by high temp 6 D reducing agent 4 C low temp 4 DX diauxic shift 7 Clustering is driven by these features ALPHA ELU CDC15 SPO HT D C DX Conflicts YM Bioinfo Problem of clustering analysis each gene can only be present in one cluster Eisen M B Spellman P T Brown P O and Botstein D 1998 Cluster analysis and display of genome wide expression pattern Proc Natl Acad Sci USA 95 14863 14868 YM Bioinfo How to solve this problem by bioinformatics methods Components identification Microarray data analysis Event discovery Text mining database integration Pathway reconstruction Database integration knowledge management Pathway interaction Circuits Simulation and systems biology YM Bioinfo All the protein protein interaction found above can be observed in MAPK pathway 115E602E 85E9952EDIP ID 226 6160166 116BIND ID RAF1 MAP2K1 HRAS RAF1 SOS1 HRAS BRB2 SOS1 EGFR GRB2 EGF EGFR Interacting pairs unique to DIP unique to BIND found in both YM Bioinfo How to solve this problem by bioinformatics methods Components identification Microarray data analysis Event discovery Text mining database integration Pathway reconstruction Database integration knowledge management Pathway interaction Circuits Simulation and systems biology YM Bioinfo Knowledge management is essential for making inference Components gene transcripts proteins Cellular location Tissue Qty of gene expression Interaction etc Time Sequence information decompress Presentation of Life YM Bioinfo One component may be precisely described by a set of terms Molecule status location component ID YM Bioinfo ReactantProduct Enzyme Component1Component3 Component2 Reactions describes the relation among components S00006 S00008 S00007 SR00005 YM Bioinfo Integrating the histology information is useful for understanding disease mecha