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ISMB 2005 Detroit, June 27 th 2005 Proteome 1

Michal Linial Institute of Life Sciences The Hebrew University Jerusalem, Israel Computer Science and Engineering University of Washington, Seattle. ISMB 2005 Detroit, June 27 th 2005 Proteome 1. Proteome – by the dictionary. The term proteome , coined in 1994.

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ISMB 2005 Detroit, June 27 th 2005 Proteome 1

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  1. Michal Linial Institute of Life Sciences The Hebrew University Jerusalem, Israel Computer Science and Engineering University of Washington, Seattle ISMB 2005 Detroit, June 27th 2005 Proteome 1

  2. Proteome – by the dictionary • The term proteome, coined in 1994. • A linguistic equivalent to the concept of genome • Proteome - complete set of proteins that is expressed, and modified by the entire genome in the lifetime of a cell. • Practical: the complement of proteins expressed by a cell at any one time.

  3. Proteomics – by the dictionary Proteomics (Practical) - the study of the proteome using technologies of large-scale protein separation and identification. Large scale separation : 2DE Liquid Chromatography Identification : MALDI MS Tandem MS/MS FT-MS ….. Still to do: Imaging, Standardization, S/N…

  4. Proteomics by Medline maturation of a field From220publications in the previous millennium (‘94-’99) To 21,350 (!!!) publications in this millennium (‘00-’05) 1730

  5. Proteomics –by Google the ultimate truth.. Proteomics 886,000 hits (2004) 4,700,000 hits (2005) Genomics 2,070,000 hits (2004) 16,000,000 hits (2005)

  6. Genome Genomics Protein Science Biochemistry Structural proteome Cell Biology Imaging Database Application Molecular evolution Biotechnology Nanotechnology Data Mining Chemistry Proteomics – in view of other fields Proteome Proteomics

  7. Proteomics –Genomics Some fundamental differences Encoded information Partially encoded

  8. Proteomics – Genomics Even more different… Handle Tech HTP PCR – amplification No PCR equivalent

  9. Protein Function is Context dependent

  10. Sequence space 2,000,000 Structure space 20,000 Function space 30,000 (function by GO) Challenge Isequence, structure and function

  11. Challenge IIthe building blocks Domain Boundaries?? Domain Interaction ?? Domain and Function ??

  12. Challenge IIIthe modification PTM identification?? PTM modeling, dependency ?? PTM and interaction ??

  13. Challenge IVMS - measurements Signal to noise ?? Quantification ?? Organelle proteomics ?? Scoring and Accuracy Efficient searching

  14. Challenge VP2P Accuracy, FP ?? Pathway and Networks ?? Context dependency ?? Network robustness ??

  15. Expectation I: Clever protein chemistry (sophisticated protein chemists/ biochemist) Differential labeling (comparative study) Affinity labeling – improved purification Improved quantification Expectation II: Better Imaging (sophisticated optics, coloring, recording, analyses)

  16. Impact of Proteomics on Human Health Proteomic as diagnostic tool Proteomicsof disease (plasma , urine, CSF) Proteomics for pathogen ID proteomics (cancer, stem cells..) Drug impact (metabolic, disease progression) Diagnostic Protein Chip, Modification chip

  17. Signaling Phospho. Endocytosis P2P A patch of receptors Life time Proteosome action Localization A pool of receptors PTM Ubiquitination of receptors Why bother… Example GABA - the major inhibitory NT in the brain GABA related to Anxiety, mood disorder, epilepsy, Parkinson, Sleep… No signal at the genome/ transcriptome levels Controlling the level of GABA response How?

  18. Proteome –ISMB Summary …and another sign of maturation 2004: 31 submission (only 16 full papers) 2005: 46 submission (Structure, Pathways - not included) MS and 2D related analysis 10 Protein-interaction 9 Protein Prediction Analysis 8 Seq to function Annotation 7 Specific Protein Families 5 Localization related 3 Others (modeling..) 4

  19. What’s next Classifying Noisy Data The Ig case Yu et al Protein Function Prediction- Kernels Borgwardt at al Substrate Prediction – Caspase Garay-Malpartida et al ****************************** Transmembrane domains for classification Sdaka & Linial Protein-protein Interaction and NMR Mettu et al

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