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A novel Method of Signaling Pathway Prediction

A novel Method of Signaling Pathway Prediction. How to build function flow model ? Functions have their own direction !!!. Woo-Hyuk Jang, I.S.I. LAB. In the Winter Workshop…. Research direction. New concept. Challenges. KEGG Features. 1. Six months…. After. 2. Contents. Introduction

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A novel Method of Signaling Pathway Prediction

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  1. A novel Method of Signaling Pathway Prediction How to build function flow model ? Functions have their own direction !!! Woo-Hyuk Jang, I.S.I. LAB.

  2. In the Winter Workshop… • Research direction • New concept • Challenges • KEGG Features 1

  3. Six months… After 2

  4. Contents • Introduction • Related works (new) • Method • Function flow model • Extract sub-networks from PPI • Implementation • Evaluation 3

  5. Introduction • Why pathway? • Biological pathways provide significant insights of molecules’ interaction mechanism • Many essential pathways still remain unknown or incomplete for newly sequenced organisms • Why signaling transduction pathway? • Is part of metabolic pathway • Is a process describing a cell change by external stimulus, and it plays an important roll of most fundamental cellular process • Since most of components are proteins, easy to start • We can extend research to metabolic pathway 4

  6. Related Works Finding Functional Patterns from PPI • Mehmet E Turanalp and Tolga Can (CS, Turkey), “Discovering functional interaction patterns in protein-protein interaction networks”, BMC Bioinformatics, 2008, 9:276 Respect to MIPS Respect to KEGG 5

  7. Related Works PFT (Pathway Functionality Template) • Ali Cakmak and Gultekin Ozsoyoglu(CS, USA), “Mining biological networks for unknown pathways”, BIOINFORMATICS, 2007, 23:20. 6

  8. Still we have challenges 7

  9. Methods A4D1K5, Q99835 Q68DJ6, Q9ULC3 Q13635, Q9Y6C5 Q14623, Q43323, … (4) P98164 LRP2 SHH (HPE3, HLP3) PTCH2 RAB23 SMO (SMOH) GO:0015485, GO:0005113, GO:0043237 GO:0005515, GO:0004872, GO:0004888 GO:0005515, GO:0005515, GO:0004872 Unknown activation binding/association inhibition dissociation GO:0005515, protein binding GO:0004872, receptor activity GO:0004888, transmembrane receptor activity GO:0015485, cholesterol binding GO:0005113, patched binding GO:0043237, laminin-1 binding dissociation dissociation dissociation 8

  10. Methods Hedgehog Ko04340 9

  11. Methods Decide Start Nodes To next candidate Recursively Is their path ? Find Neighbors Is it End Cond.? Reference Function Flow Add to New Pathway End 10

  12. Methods • Start / End node selection • Proteins which have descendant term of “Membrane” in cellular component and “Signal transducer activity” in molecular function (3841 for H. sapiens) • Proteins which have descendant term of “Transcription regulatory activity” in molecular function (921 for H. sapiens) • Extract sub-network • Should be formalized • starter, closure, completeness of sub-network, navigation rule 11

  13. Methods GO:3 4 GO:1 7 5 GO:6 6 2 GO:4 GO:8 GO:5 8 GO:7 GO:3 GO:8 GO:3 GO:4 GO:7 Start GO:1 GO:2 GO:5 GO:7 GO:3 GO:5 However, proteins used in signaling pathway are not reported their interaction Start GO:1 GO:2 GO:4 GO:5 GO:7 GO:3 GO:5 GO:8 12

  14. Implementation 13

  15. Evaluation Plan • Currently 1023 flows were modeled from 11 different signaling transduction pathway • Most of flows which have high frequency are Protein-binding to Protein-binding relation (phosphorylation 35, activation 29, compound 16) • Recently database and extracting method are enormously changed, so all statistical values should be changed • Measure precision / recall value to predict signal pathway of S1 using function flow model extracted from other pathway • Measure two different categories, Vertex overlap and Edge fidelity • STRING, HPRD interaction will be added 14

  16. Conclusion • Our research direction is going in the middle of emerging trend (Recently, a few papers are introduced) • However, what we need is SPEED!!! • Formal annotations are not yet devised • To evaluate we need more protein interactions • We expect that many ideas will be earned from new application 15

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