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ISMB/ECCB 2004. Intelligent Systems for Molecular Biology European Conference on Computational Biology ~2000 participants 8 keynote speakers 50 long and 17 short talks published in Bioinformatics 20, Suppl 1 900 posters. PT 9-04. Keynote Speakers. Leroy Hood : Systems biology
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ISMB/ECCB 2004 • Intelligent Systems for Molecular Biology • European Conference on Computational Biology • ~2000 participants • 8 keynote speakers • 50 long and 17 short talks • published in Bioinformatics 20, Suppl 1 • 900 posters PT 9-04
Keynote Speakers • Leroy Hood: Systems biology • Dennis Noble: Heart rhythm simulation • EricGreen: Multiple species comparison to decode the human genome • Svante Pääbo: Primate transcriptome evolution
Keynote Speakers • Matthias Mann: Organellar & Time resolved proteomics • Anna Tramontano: Protein structure prediction • Uri Alon: Simplicity in complex networks • David Lipman: Message & meaning in sequence comparison
Keynote Speaker: EricGreen Multiple species comparison to decode the human genome – CFTR pilot study • 1600 multiplely conserved sequences (MCS) in 1.8 Mb CFTR region • 22% CDS, 3.5 % UTR, 2.5 % repeats • 72 % unknown function, mostly unique • 66 % of MCS mentioned in literature • Approach does not detect lineage-specific elements
Multiple species comparison Which organism gives most information, when compared to man? • Gap in metazoan evolutionary tree: mammals vs. others • Marsupials and monotremes seem to fill the gap and should be sequenced • Best choice: Platypus, bargain: chicken • Fugu: good for CDS, not for other elements
Keynote Speaker: UriAlon Simplicity in complex networks • Most genes one step from transcription factor • Certain network patterns appear more often than expected: • FFL: feed forward loop (40 x in E. coli, 74 in yeast) • IFFL: Incoherent feed forward loop • SIM: single input module • DOR: densely overlapping regulons
Network pattern functions • Feed forward loop: • Asymmetric filter for transient signals allowing fast shutdown • Incoherent feed forward loop: • Pulse generator
Network pattern functions • Single input module: • Just in time production, matching temporal gene expression • flagellar synthesis • Densely overlapping regulons: • Resemble hardwired decision making systems • carbon utilization • osmotic stress response
ISMB/ECCB 2004 topics • Data mining • Data visualization • Databases • Functional genomics • Genome annotation • Microarrays • New frontiers • Phylogeny and evolution • Predictive methods • Sequence comparison • Structural biology • Systems biology PT 9-04
Database maintenance and curation problems • Data depositories (Genbank, Swiss-Prot, ..) are flooded by whole genome sequencing projects • Manual annotation and curation not feasible • Automatic annotation and curation error-prone • improved sequence annotation and prediction software needed
Coin and Durbin: Pseudogene Identification • Pseudogenes • often mis-annotated • regarded as fossils, but: • Expressed pseudogenes (2-3%) may be functional as regulatory RNAs • Yano et al. J Mol Med 82: 414 (2004) • PSILC: improved identification by including Pfam domain information
Dieterich et al.: Functional inference oftranscription factor binding sites (TFBS) • Prediction of conserved TFBS using CORG (http://corg.molgen.mpg.de) combine with • Cell cycle phase assignment (Whitfield) • 22 non-exonic and 11 5'-UTR functional TFBS predicted
Data mining • Reactome – biological processes in man knowledgebase (http://www.reactome.org/) • H-Invitational Database (H-Inv DB) (http://www.h-invitational.jp)
New frontiers Data integration: • GRID computing: workflows • Data access via web services • Simple Object Access Protocol(SOAP) (messaging protocol for transporting information) • Web Services Description Language (WSDL)
Databases • cPath: Cancer pathway database (www.cbio.mskcc.org/cpath/) • Online Predicted Human Interaction Database (http://ophid.utoronto.ca/) • Bioinformatics knowledge database (https://apps.bioneq.qc.ca/twiki/bin/view/Knowledgebase/)
Functional genomics • Comparative mouse genomics center consortium genotype database (http://mrages.niehs.nih.gov/genotype) • INCLUSive webportal: analysis of gene expression and discovery of cis-regulatory elements (http://www.esat.kuleuven.ac.be/inclusive)
Predictive methods • Darogan – Enzyme function prediction from conserved functional residues (http://www.darogan.com/) • Phobius – combined TM topology and signal peptide predictor (http://phobius.cgb.ki.se/)
Structural biology • Macromolecular Structure Database (MSD) (http://www.ebi.ac.uk/msd/index.html)
Systems biology • SciPath – Integrated environment for SB analysis (http://www.ucl.ac.uk/oncology/MicroCore/scipath.htm) • Pathway and interaction network modeling