shuang liang ● southern medical university building a knowledge discovery system
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Shuang Liang ● Southern Medical UniversityShuang Liang ● Southern Medical University
Building a Knowledge Discovery System
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 ProustMarcel Proust
Eying a picture is better than seeing a thousand words
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Uncover the hidden linksUncover the hidden links
DiseaseSymptom
GeneProteinmiRNA
SM DrugTCM
Data Knowledge
Bioinformatics
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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
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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 SourcesData Sources
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Gene Y
Expression Profiling of TSGExpression Profiling of TSGGene X
Tissue Types
Tissue Specific
Tissue Selective
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~130 Tissues~4000 Samples
TSG Mining
GeneLogic+ Novartis
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liverCOXPRESdb
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 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
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Functional ModulesFunctional Modules
Batch View
Tissue View Multiple View
Title in hereGene View
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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
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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
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Discovery : From Drug to Diseases Discovery : From Drug to Diseases
Simvastatin:hypercholesterolemiacardiovascular disease
p < 1E-5
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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
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Gene
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Literature mining
Gene
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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
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PFM
TFBSTFBS
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TFBS PredictionTFBS Prediction
研究策略
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MAXLaps : TFBS Prediction ToolMAXLaps : TFBS Prediction Tool
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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
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T1 T2 T3
TFBS PFMCRM1.........CRMk
TFBS Prediction for TSGTFBS Prediction for TSG
CRM:
Tis
sue
type
s
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Future PlanFuture 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 UniversityShuang Liang ● Southern Medical University
Xiaoqin Yang
Xia ChenGuiping WangYun Ye
Xuezhong Zhou
NCBIKEGGReactomeMGILocateDrugbankGO……
NSFC
GD EA
SMU