Shuang Liang ● Southern Medical University Building a Knowledge Discovery System

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

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

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

 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

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

~130 Tissues ~4000 Samples TSG Mining GeneLogic + Novartis

liver COXPRESdb liver Novatis Human tissue compendium

Disease-TSG Drug-TSG Disease-Drug Making the connection

symptom Prescription TCM Component

Data TypeNumber Tissue/Cell types127 TSGs3960 TSG - Disease relationships5672 TSG - Drug relationships2171 TSG - Subcellular Localization3687 TSG - GO annotation47418 TSG - Pathway6359 TSG - Mammalian Phenotype32397

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

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

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, p < 0.05

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

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, p < 0.05

Gene

Literature mining Gene

Drug Pathway Localiza- tion DiseaseGene KDS  – drugbank 562 – C-Map 544 – Compound  TCM  – drugbank – non-TSG 2741 – gene set 611 – miRNA  – MeSH+OMIM 86 – TCM symptom 8703 – mammalian phenotype  – TSG-related – gene ~ Go CC  – KEGG + Reactome – gene ~ pathway Still growing

PFM TFBS

TFBS Prediction 研究策略

MAXLaps ： TFBS Prediction Tool

MotifMEMENMICAthis study HLF 200 bpYes 800 bpNo Yes C-FOS 200 bpYes 600 bpNo Yes HFH bpYes 1400 bpNo Yes Human Gene TFBS Prediction

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

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

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