Shuang Liang ● Southern Medical UniversityShuang Liang ● Southern Medical University

Building a Knowledge Discovery System

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 ProustMarcel Proust

Eying a picture is better than seeing a thousand words

Uncover the hidden linksUncover the hidden links

DiseaseSymptom

GeneProteinmiRNA

SM DrugTCM

Data Knowledge

Bioinformatics

FocusFocus

Data Mining

Data Integration

Platform Building

TranslationalResearch

Mining Clinicaldata, 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 SourcesData Sources

Gene Y

Expression Profiling of TSGExpression Profiling of TSGGene X

Tissue Types

Tissue Specific

Tissue Selective

~130 Tissues~4000 Samples

TSG Mining

GeneLogic+ Novartis

liverCOXPRESdb

liver

Novatis Human tissue compendium

Disease-TSG

Drug-TSG

Disease-Drug

Making the connection

symptom

Prescription

TCM

Component

Data Type Number

Tissue/Cell types 127

TSGs 3960

TSG - Disease relationships 5672

TSG - Drug relationships 2171

TSG - Subcellular Localization 3687

TSG - GO annotation 47418

TSG - Pathway 6359

TSG - Mammalian Phenotype 32397

Functional ModulesFunctional Modules

Batch View

Tissue View Multiple View

Title in hereGene View

Discovery: From Diseases to DrugDiscovery: From Diseases to Drug

Enrichment (p < 1E-5)：immune responseinflammatory responseCytokine-cytokine interactionToll-like receptor signaling

p < 1E-5

p < 1E-5

Discovery: From Diseases to DrugDiscovery: From Diseases to Drug

TNF inhibitor ：EtanerceptAdalimumab

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

Discovery ： From Drug to Diseases Discovery ： From Drug to Diseases

Simvastatin：hypercholesterolemiacardiovascular disease

p < 1E-5

Discovery ： From Drug to Diseases 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

Gene

Literature mining

Gene

Drug

Pathway

Localiza-tion

Disease

Gene

KDS

– drugbank562 – C-Map544 – Compound1305+ TCM

– drugbank17119 – non-TSG2741 – gene set611 – miRNA

– MeSH+OMIM86 – TCM symptom8703 – mammalian phenotype

– TSG-related52532 – gene ~ Go CC

– KEGG + Reactome38611 – gene ~ pathway

Still growing

PFM

TFBSTFBS

TFBS PredictionTFBS Prediction

研究策略

MAXLaps ： TFBS Prediction ToolMAXLaps ： TFBS Prediction Tool

Motif MEME NMICA this study

HLF200 bp Yes Yes Yes

800 bp No No Yes

C-FOS200 bp Yes Yes Yes

600 bp No No Yes

HFH-1800 bp Yes Yes Yes

1400 bp No No Yes

Human Gene TFBS PredictionHuman Gene TFBS Prediction

T1 T2 T3

TFBS PFMCRM1.........CRMk

TFBS Prediction for TSGTFBS Prediction for TSG

CRM:

Tis

sue

type

s

Future PlanFuture Plan

More data collection & integration

Multiple verticals & prioritization

Mining capability & feature enrichment

Hypothesis generation & validation

Translational use

Collaboration

Shuang Liang ● Southern Medical UniversityShuang Liang ● Southern Medical University

Xiaoqin Yang

Xia ChenGuiping WangYun Ye

Xuezhong Zhou

NCBIKEGGReactomeMGILocateDrugbankGO……

NSFC

GD EA

SMU