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Transcript
Building a Knowledge Discovery System Shuang Liang ● Southern Medical University Marcel Proust The real act of discovery consists not in finding new lands but in seeing with new eyes - Marcel Proust Eying a picture is better than seeing a thousand words Uncover the hidden links Bioinformatics Data Gene Protein miRNA Knowledge Disease Symptom SM Drug TCM Focus Data Mining Data Integration Platform Building Translational Research Omics, Literature, HT Analytical pipeline, Mining Clinical & HT data, Annotation, Drug screening, TCM, Target ID,database, Structure, records/images algorithm, prediction/analytical tools Sequence, Literature etc. Medical Diagnosis, Prognosis Data Sources PubMed KEGG iHOP DrugBank GO Locate OMIM MGI HT data Literature Structure NCBI - GEO GenBank EBI – ArrayExpress Transfac NextGen Sequencing miRBase Connectivity Map InterPro GWAS/SNP/aCGH TarFisDock Others Expression Profiling of TSG Gene X Tissue Specific Gene Y Tissue Selective Tissue Types TSG Mining ~130 Tissues ~4000 Samples GeneLogic + Novartis COXPRESdb Novatis Human tissue compendium liver liver Drug-TSG Disease-Drug Making the connection Disease-TSG symptom Component Prescription TCM Data Type Tissue/Cell types Number 127 TSGs TSG - Disease relationships 3960 5672 TSG - Drug relationships TSG - Subcellular Localization TSG - GO annotation 2171 3687 47418 TSG - Pathway 6359 TSG - Mammalian Phenotype 32397 Functional Modules Batch View Tissue View Multiple View Gene Title inView here 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 Discovery: From Diseases to Drug p < 0.05 TNF inhibitor ： Etanercept Adalimumab Ortiz P, Bissada NF et 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. Discovery：From Drug to Diseases p < 1E-5 Simvastatin： hypercholesterolemia cardiovascular disease 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. Gene Literature mining Gene 4324 – drugbank 562 – C-Map 544 – Compound 1305+ - TCM 3960 – drugbank 17119 – non-TSG 2741 – gene set 611 – miRNA Drug Pathway 880 – KEGG + Reactome 38611 – gene ~ pathway Gene 15188 – MeSH+OMIM 86 – TCM symptom 8703 – mammalian phenotype KDS Still growing Disease Localiza3687 – TSG-related tion 52532 – gene ~ Go CC TFBS PFM TFBS Prediction 研究策略 MAXLaps：TFBS Prediction Tool Human Gene TFBS Prediction Motif HLF C-FOS HFH-1 MEME NMICA this study 200 bp Yes Yes Yes 800 bp No No Yes 200 bp Yes Yes Yes 600 bp No No Yes 800 bp Yes Yes Yes 1400 bp No No Yes TFBS Prediction for TSG TFBS PFM CRM1 Tissue types . . . . . . . . . CRMk CRM: T1 T2 T3 Future Plan More data collection & integration Multiple verticals & prioritization Mining capability & feature enrichment Hypothesis generation & validation Translational use Collaboration Xiaoqin Yang Xia Chen Guiping Wang Yun Ye Xuezhong Zhou Shuang Liang ● NCBI KEGG Reactome MGI Locate Drugbank GO …… NSFC GD EA SMU Southern Medical University
