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An overview of Bioinformatics. Cell and Central Dogma. Source: “Post-genome Informatics” by M Kanehisa. Source: “Post-genome Informatics” by M Kanehisa. Deduction and Analogy. Biological System (Organism) Reductionistic Synthetic
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Biological System (Organism) Reductionistic Synthetic Approach Approach (Experiments) (Bioinformatics) Building Blocks (Genes/Molecules) Source: “Post-genome Informatics” by M Kanehisa
Principles Known Physics Chemistry Biology Matter Compound Organism Elementary Elements Genes Particles Yes Yes No Source: “Post-genome Informatics” by M Kanehisa
Searching and learning problems in biology Source: “Post-genome Informatics” by M Kanehisa
Homology Search New sequence Sequence database (Primary data) retrieval Similar sequences Expert knowledge Sequence interpretation Source: “Post-genome Informatics” by M Kanehisa
Pairwise sequence alignment by dynamic programming Needleman Wunsch alogrithm Source: “Post-genome Informatics” by M Kanehisa
Database Search for Similar Sequences
Source: “Introduction to Protein Structure” by Branden & Tooze
Motif Search Sequence database (Primary data) New sequence Expert knowledge Motif library (Empirical rules) inference Sequence interpretation Source: “Post-genome Informatics” by M Kanehisa
Introduction to Structural Biology
Source: “Introduction to Protein Structure” by Branden & Tooze
Source: “Introduction to Protein Structure” by Branden & Tooze
Genome Sequencing and Genome Annotation
A general model of the structure of genomicsequences Source: “Bioinformatics” by D W Mount
Joe Sutliff for Science 291 p1224 (2001) What kind of solution Genomics can provide with ? High Throughput Gene Discovery
165 genes are up-regulated in 75% tumors (MAPK pathway, APC, promotion of mitosis; 69 unknown) • 170 genes are down-regulated in 65% tumors (hepatocyte-specific gene products, retinoid metabolism; 75 unknown) • Hierarchical Clustering • K-means • Self Organization Map • Support Vector • Single Value Decomposition
Gene Expression and Transcriptome
Proteomics and Functional Genomics
Living Cell Perturbation Environmental change Gene disruption Gene overexpression Dynamic Response Changes in: Gene expression profiles, Etc. Biological Knowledge Molecular and Cellular Biology,Biochemistry, Genetics, etc Basic Principles Practical Applications Virtual Cell Complete Genome Sequences Source: “Post-genome Informatics” by M Kanehisa
Take Home Message • Define the biological problem. • Why is bioinformatics important ? A synthesis approach. • Prediction is a dangerous game. Always try your best to validate in the bench side. • The devil is in the detail. Always try different bioinformatic tools and databases. • Your knowledge rests on your own practice.
Reference Books you will find useful: Bioinformatics -sequence and genome analysis by D W Mount Introduction to Bioinformatics by A M Lesk Post-genome Informatics by M Kanehisa
Evolution of molecular biology databases Database category Data content Examples 1. Literature database Bibliographic citations MEDLINE(1971) On-line journals 2. Factual Database Nucleic acid sequences GenBank(1982) Amino acid sequences EMBL(1982) 3D molecular structures DDBJ(1984) SWISS_PROT(1986) PDB(1971) 3. Knowledge base Motif libraries PROSITE(1988) Molecular classification SCOP(1994) Biochemical pathways KEGG(1995)