biological networks - building and visualizing

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August 22 nd , 2013 Vijayaraj Nagarajan PhD Computational Biologist BCBB/OCICIB/NIAID, National Institutes of Health

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Page 1: Biological networks - building and visualizing

August 22nd, 2013

Vijayaraj Nagarajan PhD Computational Biologist BCBB/OCICIB/NIAID, National Institutes of Health

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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)  

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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)  

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Available  Interac0on  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  

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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)    §  GeneMANIA  §  BIOBASE  §  IPA  (Ingenuity  Pathway  Analysis)  § MetaCore  

Open Source

Proprietary

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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  

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Searching  for  Interac0on  Data  

STRING  IPA  

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IPA  

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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)  

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– Cytoscape  – VisANT  (Integra)ve  Visual  Analysis  Tool)  – Osprey  – BioLayout  

Popular  Visualiza0on  Tools  

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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)  

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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)  

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PPI  Predic0on  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  

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PPI  Predic0on  Using  Microarray  Data  

§ Melanoma  metastasis  –  83  samples  –  Affymetrix  –  GEO  –  ARACNE  –  geWorkbench  –  IP3R1,  IP3R2,  IP3R3,  STIM1,  ORAI1  

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GML File

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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  

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Visualiza0on  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  

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Literature  Based  PPI  Predic0on    Using  Cytoscape  

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Retrieving  PPI  Using  Cytoscape  

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Data  Visualiza0on,  Integra0on,  Analysis  –  Import  ARACNE  predicted  network  –  Import  VisANT  retrieved  network  –  Merge  all  networks  –  Mo)f  finding  

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[email protected]

Thank  You