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August 22nd, 2013
Vijayaraj Nagarajan PhD
Computational Biologist
BCBB/OCICIB/NIAID, National Institutes of Health
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)	
  
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)	
  
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	
  
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
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	
  
Searching	
  for	
  Interac0on	
  Data	
  
STRING	
  
IPA	
  
IPA	
  
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)	
  
– Cytoscape	
  
– VisANT	
  (Integra)ve	
  Visual	
  Analysis	
  Tool)	
  
– Osprey	
  
– BioLayout	
  
Popular	
  Visualiza0on	
  Tools	
  
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)	
  
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)	
  
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	
  
PPI	
  Predic0on	
  Using	
  Microarray	
  Data	
  
§  Melanoma	
  metastasis	
  
–  83	
  samples	
  
–  Affymetrix	
  
–  GEO	
  
–  ARACNE	
  
–  geWorkbench	
  
–  IP3R1,	
  IP3R2,	
  IP3R3,	
  STIM1,	
  ORAI1	
  
GML File
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	
  
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	
  
Literature	
  Based	
  PPI	
  Predic0on	
  	
  
Using	
  Cytoscape	
  
Retrieving	
  PPI	
  Using	
  Cytoscape	
  
Data	
  Visualiza0on,	
  Integra0on,	
  Analysis	
  
–  Import	
  ARACNE	
  predicted	
  network	
  
–  Import	
  VisANT	
  retrieved	
  network	
  
–  Merge	
  all	
  networks	
  
–  Mo)f	
  finding	
  
60
61
62
63
64
nagarajanv@mail.nih.gov
Thank	
  You	
  

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Biological networks - building and visualizing

  • 1. August 22nd, 2013 Vijayaraj Nagarajan PhD Computational Biologist BCBB/OCICIB/NIAID, National Institutes of Health
  • 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. 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)  
  • 4. 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  
  • 5. 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
  • 6. 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  
  • 7. Searching  for  Interac0on  Data   STRING   IPA  
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  • 23. 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)  
  • 24. – Cytoscape   – VisANT  (Integra)ve  Visual  Analysis  Tool)   – Osprey   – BioLayout   Popular  Visualiza0on  Tools  
  • 25. 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)  
  • 26. 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)  
  • 27. 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  
  • 28. PPI  Predic0on  Using  Microarray  Data   §  Melanoma  metastasis   –  83  samples   –  Affymetrix   –  GEO   –  ARACNE   –  geWorkbench   –  IP3R1,  IP3R2,  IP3R3,  STIM1,  ORAI1  
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  • 41. 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  
  • 42. 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  
  • 43. Literature  Based  PPI  Predic0on     Using  Cytoscape  
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  • 47. Retrieving  PPI  Using  Cytoscape  
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  • 51. Data  Visualiza0on,  Integra0on,  Analysis   –  Import  ARACNE  predicted  network   –  Import  VisANT  retrieved  network   –  Merge  all  networks   –  Mo)f  finding  
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