Building a Knowledge Discovery System

1. Building a Knowledge Discovery System

2. Marcel Proust The real act of discovery consists not in finding new landsbut in seeing with new eyes - Marcel Proust Eying a picture is better than seeing a thousand words

3. Uncover the hidden links Bioinformatics Data Knowledge Gene Protein miRNA SM Drug TCM Disease Symptom

4. HT Analytical pipeline, database, algorithm, prediction/analytical tools Drug screening, TCM, Target ID, Diagnosis, Prognosis Omics, Annotation, Literature, Structure, Medical records/images Mining Clinical & HT data, Sequence, Literature etc. Focus Data Mining Data Integration Platform Building Translational Research

5. Data Sources • KEGG • DrugBank • Locate • MGI • PubMed • iHOP • GO • OMIM Others Literature Structure HT data • NCBI - GEO • EBI – ArrayExpress • NextGen Sequencing • Connectivity Map • GWAS/SNP/aCGH • GenBank • Transfac • miRBase • InterPro • TarFisDock

6. A Platform for Tissue-Specific Genes and beyond

7. Gene X Gene Y Expression Profiling of TSG Tissue Specific Tissue Selective Tissue Types

8. TSG Mining ~130 Tissues ~4000 Samples GeneLogic + Novartis

10. liver COXPRESdb Novatis Human tissue compendium liver

11. Drug-TSG Disease-TSG Disease-Drug Making the connection

12. symptom Prescription Component TCM

15. Functional Modules Batch View Multiple View Tissue View Gene View Title in here

16. Discovery: From Diseases to Drug p < 1E-5 p < 1E-5 Enrichment (p < 1E-5)： immune response inflammatory response Cytokine-cytokine interaction Toll-like receptor signaling

17. Discovery: From Diseases to Drug p < 0.05 TNF inhibitor： Etanercept Adalimumab Ortiz P, Bissada NFet al Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J Periodontol 80: 535–540, 2009.

18. Discovery：From Drug to Diseases p < 1E-5 Simvastatin： hypercholesterolemia cardiovascular disease

19. Discovery：From Drug to Diseases p < 0.05 Bruner-Tran KL, Osteen KG, Duleba AJ. Simvastatin protects against the development of endometriosis in a nude mouse model. J Clin Endocrinol Metab 94: 2489–2494, 2009.

20. Gene

22. Literature mining Gene

24. Disease Gene Drug 4324 – drugbank 562 – C-Map 544 – Compound 1305+ - TCM 3960 – drugbank 17119 – non-TSG 2741 – gene set 611 – miRNA 15188 – MeSH+OMIM 86 – TCM symptom 8703 – mammalian phenotype Pathway KDS 880 – KEGG + Reactome 38611 – gene ~ pathway Still growing Localiza- tion 3687 – TSG-related 52532 – gene ~ Go CC

25. More development

26. TFBS PFM

27. TFBS Prediction 研究策略

28. MAXLaps：TFBSPrediction Tool

29. Human Gene TFBSPrediction

30. TFBS Prediction for TSG TFBS PFM CRM1 . . . . . . . . . CRMk Tissue types CRM: T1 T2 T3

31. Future Plan • More data collection & integration • Multiple verticals & prioritization • Mining capability & feature enrichment • Hypothesis generation & validation • Translational use • Collaboration

32. Thanks! Xiaoqin Yang Xia Chen Guiping Wang Yun Ye Xuezhong Zhou NCBI KEGG Reactome MGI Locate Drugbank GO …… NSFC GD EA SMU