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Shuang Liang ● Southern Medical University Building a Knowledge Discovery System
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The real act of discovery consists not in finding new lands but in seeing with new eyes - Marcel Proust Marcel Proust Eying a picture is better than seeing a thousand words
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Uncover the hidden links Disease Symptom Gene Protein miRNA SM Drug TCM Data Knowledge Bioinformatics
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Focus Data Mining Data Integration Platform Building Translational Research Mining Clinical data, Sequence, Literature etc. Omics, Annotation, Literature, Structure, Medical records/images HT Analytical pipeline, database, algorithm, prediction/analytical tools Drug screening, TCM, Target ID, Diagnosis, Prognosis
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NCBI - GEO EBI – ArrayExpress NextGen Sequencing Connectivity Map GWAS/SNP/aCGH HT data Literature Structure Others KEGG DrugBank Locate MGI PubMed iHOP GO OMIM GenBank Transfac miRBase InterPro TarFisDock Data Sources
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Gene Y Expression Profiling of TSG Gene X Tissue Types Tissue Specific Tissue Selective
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~130 Tissues ~4000 Samples TSG Mining GeneLogic + Novartis
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liver COXPRESdb liver Novatis Human tissue compendium
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Disease-TSG Drug-TSG Disease-Drug Making the connection
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symptom Prescription TCM Component
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Data TypeNumber Tissue/Cell types127 TSGs3960 TSG - Disease relationships5672 TSG - Drug relationships2171 TSG - Subcellular Localization3687 TSG - GO annotation47418 TSG - Pathway6359 TSG - Mammalian Phenotype32397
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Functional Modules Batch View Tissue View Multiple View Title in here Gene View
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Discovery: From Diseases to Drug Enrichment (p < 1E-5) : immune response inflammatory response Cytokine-cytokine interaction Toll-like receptor signaling p < 1E-5
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Discovery: From Diseases to Drug 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. p < 0.05
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Discovery : From Drug to Diseases Simvastatin : hypercholesterolemia cardiovascular disease p < 1E-5
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Discovery : From Drug to Diseases 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. p < 0.05
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Gene
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Literature mining Gene
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Drug Pathway Localiza- tion DiseaseGene KDS – drugbank 562 – C-Map 544 – Compound 1305+ TCM – drugbank 17119 – non-TSG 2741 – gene set 611 – miRNA – MeSH+OMIM 86 – TCM symptom 8703 – mammalian phenotype – TSG-related 52532 – gene ~ Go CC – KEGG + Reactome 38611 – gene ~ pathway Still growing
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PFM TFBS
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TFBS Prediction 研究策略
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MAXLaps : TFBS Prediction Tool
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MotifMEMENMICAthis study HLF 200 bpYes 800 bpNo Yes C-FOS 200 bpYes 600 bpNo Yes HFH-1 800 bpYes 1400 bpNo Yes Human Gene TFBS Prediction
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T1 T2 T3 TFBS PFM CRM1. CRMk TFBS Prediction for TSG CRM: Tissue types
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Future Plan More data collection & integration Multiple verticals & prioritization Mining capability & feature enrichment Hypothesis generation & validation Translational use Collaboration
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Shuang Liang ● Southern Medical University Xiaoqin Yang Xia Chen Guiping Wang Yun Ye Xuezhong Zhou NCBI KEGG Reactome MGI Locate Drugbank GO …… NSFC GD EA SMU
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