Biological networks

Biological networks: building, visualization and analysis

1. 1
Vijayaraj Nagarajan PhD
Computational Biologist, BCBB/OCICB/NIAID/NIH
Biological Networks :
building, visualization and analysis
OFFICE OF CYBER INFRASTRUCTURE AND COMPUTATIONAL BIOLOGY
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

2. Outline(
• Introduc)on*to*Biological*Networks*
• Basic*components*of*a*network*
• Types*of*biological*networks*
• Predic)ng/Building*Biological*Networks*
• Methods*
? Logic*and*concept*
• Available*Interac)on*data*
• Integrated*protein?protein*interac)on*databases*
• Searching*for*interac)on*data*
• Network*Visualiza)on*and*Analysis*tools*
• Popular*visualiza)on*tools*
• Network*analysis*
• Demonstra)on*
• Building,*visualiza)on*and*analysis*of*the*biological*networks*(Cytoscape)*

3. • Nodes*
o DNA/RNA/Protein/Metabolite/Ontology*
• Edges*
Directed*
o Dis)nc)on*between*source*and*target*
? Ac)va)on*(direct/indirect)*
? Repression*(direct/indirect)*
Undirected*
o No*dis)nc)on*between*source*and*target*
? Co?expression*(indirect)*
? Binding*(direct)*
? Similarity/strength*
Biological(Networks(–(Basic(Components(

4. Biological(Networks(7(Basic(Features(
• Degree*
• Number*of*connec)ons*that*a*node*has*
• Distance*
• Number*of*connec)ons*between*two*
nodes,*in*a*shortest*path*
• Path*
• A*sequence*of*connec)ons*
• Is*there*a*path*(reachability)*
• Mean*Shortest*Path*distance*(closeness)*
• In*how*many*shortest*paths*(betweenness)*

5. • Size*of*a*network*(Number*of*nodes)*
• Density*of*a*network*(Propor)on*of*the*connec)ons)*
• Mo)fs/Cliques/Clusters/Sub?networks*
Loops
Chains
Parallels
Multi-input Single input
Biological(Networks(7(Basic(Features(

6. Types(of(Biological(Networks(
• DNA?Protein*
? Transcrip)onal*regulatory*networks*
? Methyla)on*networks*
• RNA?RNA*
? miRNA*regulatory*networks*
• RNA?Protein*
? Splicing*regulatory*networks*
• Protein?Protein*
? Co?expression*networks*
? Co?localiza)on*networks*
? Co?evolu)on*networks*
? Structure*networks*
? Pathway*networks*
? Protease*regulatory*networks*
? Signal*transduc)on*networks*
? Gene*Ontology*networks*

7. Single*gene* * **
o Regulators/Co?regulators*
o Upstream/Downstream*elements*in*the*network*
o Global*connec)vity/interconnec)vity*
o Func)onal*features*
o Differen)ally*expressed*subnetworks*
o One*gene*–*one*disease*:*bunch*of*genes*–*pathways*
o Nextgen*sequencing*data*
o Meta?analysis*
List*of*genes*
Why(Build/Analyze(Biological(Networks(?(

8. Outline(
• Introduc)on*to*Biological*Networks*
• Basic*components*of*a*network*
• Types*of*biological*networks*
• Predic)ng/Building*Biological*Networks*
• Methods*
? Logic*and*concept*
• Available*Interac)on*data*
• Integrated*protein?protein*interac)on*databases*
• Searching*for*interac)on*data*
• Network*Visualiza)on*and*Analysis*tools*
• Popular*visualiza)on*tools*
• Network*analysis*
• Demonstra)on*
• Building,*visualiza)on*and*analysis*of*the*biological*networks*(Cytoscape)*

9. How(to(Build(Biological(Networks(?((
• Search/Retrieve*from*knowledge*bases*
• Predict*from*genome*sequences*
• Predict*from*lomicsz*data*
• Predict*from*literature*
• Integrate*and*analyze*
• Meta?networks*from*genome*scale*data*analysis*

10. Protein Engineering, Vol. 14, No. 9, 609-614, September 2001
PredicEon(from(genome(sequences(
• Gene*neighbor*(gene*cluster,*gene*order)*
• Gene*fusion*(RoseVa*stone)*
• Phylogene)c*profiling*
• Co?evolu)on*
• Mirror*tree*

11. PredicEon(from(lomicsz(data(
• Co?expression*(Correla)on,*Mutual*Informa)on)*
• Integrated*(Classifica)on)*
• Literature*mining*(Natural*Language*Processing)*

12. Outline(
• Introduc)on*to*Biological*Networks*
• Basic*components*of*a*network*
• Types*of*Biological*networks*
• Predic)ng/Building*Biological*Networks*
• Methods*
? Logic*and*concept*
• Available*network*data*
• Integrated*interac)on*databases*
• Searching*for*interac)on*data*
• Network*Visualiza)on*and*Analysis*tools*
• Popular*visualiza)on*tools*
• Network*analysis*
• Demonstra)on*
• Building,*visualiza)on*and*analysis*of*the*predicted*network*(Cytoscape)*

13. Available(InteracEon(Network(Data(
• MINT*
• Molecular*Interac)on*Database*
• BIND*
• Biomolecular*Interac)on*Network*Database*
• DIP*
• Database*of*Interac)ng*Proteins*
• IntAct*
• InterAc)on*Database*at*EBI*

14. Integrated(Data(Sources(
• Pathway*Commons*
• BioGRID*
• MiMI*(Michigan*Molecular*Interac)ons)*
• STRING*(Search*Tool*for*Retrieval*of*Interac)ng*Genes/Proteins)*
• Genes2Network*
• VisANT*(Integra)ve*Visual*Analysis*Tool)**
• BIOBASE*
• IPA*(Ingenuity*Pathway*Analysis)*
• MetaCore*
Open Source
Proprietary

15. IP3Rs(
• Inositol*triphosphate*receptor*
• ip3r1*
• ip3r2*
• ip3r3*
? Calcium*ion*channels*
? ER*
• s)m1*(stromal*interac)on*molecule*1)*
? PM*
? Calcium*sensor*protein*
• orai1*(calcium*release*ac)vated*calcium*modulator)*
? PM*
? Accessory*protein*downstream*of*s)m1*

16. Searching(for(InteracEon(Data(
STRING*
IPA*

25. IPA(

32. Outline(
• Introduc)on*to*Biological*Networks*
• Basic*components*of*a*network*
• Types*of*Biological*networks*
• Predic)ng/Building*Biological*Networks*
• Methods*
? Logic*and*concept*
• Available*network*data*
• Integrated*interac)on*databases*
• Searching*for*interac)on*data*
• Network*Visualiza)on*and*Analysis*tools*
• Popular*visualiza)on*tools*
• Network*analysis*
• Demonstra)on*
• Building,*visualiza)on*and*analysis*of*the*predicted*network*(Cytoscape)*

33. • Cytoscape*
• VisANT*(Integra)ve*Visual*Analysis*Tool)*
• Osprey*
• BioLayout*
Popular(VisualizaEon(Tools(

34. Analysis(Tools(
• Phunkee*(Pairing*subgraphs*Using*Network*Environment*Equivalence*–*finds*similar*
subnets)*
• mfinder*(mo)f*detec)on)*
• MAVisto*(Mo)f*Analysis*and*Visualiza)on*tool*–*explora)on*of*mo)fs)*
• GraphMatch*(Search*for*similar*sub?nets)*
• NeAT*(Network*Analysis*Tools*–*mo)f*finding,*node*sta)s)cs)*
• Cfinder*(Finds*clusters*–*dense*group*of*nodes)*
• NetworkBLAST*(Compares*mul)ple*networks*to*infer*complexes*&*paths)*

35. Outline(
• Introduc)on*to*Biological*Networks*
• Basic*components*of*a*network*
• Types*of*Biological*networks*
• Predic)ng/Building*Biological*Networks*
• Methods*
? Logic*and*concept*
• Available*network*data*
• Integrated*interac)on*databases*
• Searching*for*interac)on*data*
• Network*Visualiza)on*and*Analysis*tools*
• Popular*visualiza)on*tools*
• Network*analysis*
• Demonstra)on*
• Building,*visualiza)on*and*analysis*of*the*predicted*network*(Cytoscape)*

36. PPI(PredicEon(Using(Microarray(Data(
• Co?expression*concept*
• Correla)on*Coefficient*
? SIMoNE*(Sta)s)cal*Inference*for*Modular*Networks)*?*R*
• Mutual*Informa)on*
? Reference*Networks*
? ARACNE*(Algorithm*for*Reconstruc)on*of*Accurate*Cellular*Networks)*–*R,*
geWorkbench*
? CLR*(Context*Likelihood*of*Relatedness)*–*R*
? MRNET*(Maximum*Relevance/Minimum*Redundancy)*–*R*
? MONET*(Modularized*NETwork*Learning)*?*Cytoscape*
• Bayesian*Network*

37. PPI(PredicEon(Using(Microarray(Data(
• Melanoma*metastasis*
• 83*samples*
• Affymetrix*
• GEO*
• ARACNE*
• geWorkbench*
• IP3R1,*IP3R2,*IP3R3,*STIM1,*ORAI1*

49. GML File

50. Predicted(PPI(Network(
• Could*form*a*complex*
• Could*be*func)onally*associated*
• Could*be*involved*in*a*same*metabolic*pathway*
• Could*be*involved*in*a*specific*signal*transduc)on*path*
• False*posi)ve*

51. VisualizaEon(and(Analysis(Using(Cytoscape(
• Cytoscape*
• Opensource*
• Works*in*Windows,*Linux,*Mac*
• One*of*the*first*developed*tools*
• Great*number*of*PLUGINS*
• Excellent*help*from*community*

52. Literature(Based(PPI(PredicEon((
Using(Cytoscape(

56. Retrieving(PPI(Using(Cytoscape(

60. Data(VisualizaEon,(IntegraEon,(Analysis(
• Import*ARACNE*predicted*network*
• Import*VisANT*retrieved*network*
• Merge*all*networks*
• Mo)f*finding*

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72. [email protected]
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Thank(You(