NetBioSIG2014-Talk by Yu Xia

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NetBioSIG2014 at ISMB in Boston, MA, USA on July 11, 2014

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NetBioSIG2014-Talk by Yu Xia

  1. 1. Signatures  of  pleiotropy,  economy  and     convergent  evolu6on  in  a  domain-­‐resolved  map  of   human-­‐virus  protein-­‐protein  interac6on  networks   Yu  (Brandon)  Xia   Department  of  Bioengineering   McGill  University   Eric  Franzosa  Sara  Garamszegi  
  2. 2. Between-­‐species  systems  biology   H H H H H H H H H V H Human Protein Virus Protein Sequence Homology Known Interaction Stable Complex V H H H HV H H H V (a) (b) (c) V   V   V   V   •  Within-­‐human  PPI  network:  endogenous   •  Human-­‐virus  PPI  network:  exogenous   2  [Uetz,  2006;  Calderwood,  2007;  Dyer,  2008;  etc.]  
  3. 3. Between-­‐species  structural  systems  biology   H H H H H H H H H V H Human Protein Virus Protein Sequence Homology Known Interaction Stable Complex V H H H HV H H H V (a) (b) (c) V   V   V   V   •  Within-­‐human  PPI  network:  endogenous   •  Human-­‐virus  PPI  network:  exogenous   3   Template-­‐based  modeling   [Franzosa  and  Xia,  PNAS  2011]  
  4. 4. Within-­‐human  and  human-­‐virus   structural  interac6on  networks   53  exogenous  interac6ons   3,039  endogenous  interac6ons   4   [Franzosa  and  Xia,  PNAS  2011]  
  5. 5. Virus  proteins  tend  to  bind  to  exis6ng   endogenous  interfaces   [Franzosa  and  Xia,  PNAS  2011]   5   H   H   V  
  6. 6. Proper6es  of  mimicked  interfaces   •  Endogenous  interfaces  mimicked  by  virus  proteins  tend  to  involve  regulatory   ac6vi6es,  transient  binding,  and  parWcipate  in  mul6ple  endogenous   interac6ons   •  Viruses  target  high-­‐level,  regulatory  components  of  the  cellular  circuitry   6   H   H   H   H   H   V   H   H   V   H   H   H   V   H   [Franzosa  and  Xia,  PNAS  2011]  
  7. 7. Viral  binding  accelerates  endogenous   interface  evolu6on   [Franzosa  and  Xia,  PNAS  2011]   7  
  8. 8. 8   Two  types  of  protein-­‐protein  interac6ons   Domain-­‐domain  interac6on    Domain-­‐mo6f  interac6on  
  9. 9. 9   Case  studies   [Davey,  Travé,  Gibson,  Trends  Biochem  Sci  2011]  
  10. 10. 10   A  domain-­‐resolved  map  of  human-­‐human  and   human-­‐virus  protein-­‐protein  interac6on  networks   [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  11. 11. 11   Domain-­‐resolved  interac6ons  are  of  high  quality   [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  12. 12. 12   Binding  site  mimicry  evolves  differently  in  virus  and   human  proteins   [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  13. 13. 13   Viral  proteins  tend  to  target  human  proteins   containing  linear  mo6f-­‐binding  (LMB)  domains     [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  14. 14. 14   Viruses  tend  to  target  human  proteins  containing   LMB  domains,  independent  of  host  protein  degree     [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  15. 15. 15   Viral  proteins  have  a  higher  frac6on  of  domain-­‐mo6f   interac6ons  than  human  proteins   [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]  
  16. 16. 16   Viral  proteins  target  LMB  domains  at   greater  density  than  human  proteins   [Garamszegi,  Franzosa,  Xia,  PLoS  Pathogens  2013]   Our  domain-­‐ resolved  network   CCSB  interactome   network  
  17. 17. Three  design  principles  of  the  domain-­‐ resolved  human-­‐virus  protein-­‐protein   interac6on  network   •  Human-­‐virus  PPI  network  is  antagonis6c   •  Human-­‐virus  PPI  network  is  economical   •  Human-­‐virus  PPI  network  is  strongly  shaped  by  convergent   evolu6on   •  Most  of  these  signatures  are  only  apparent  at  high  resoluWon   17  
  18. 18. Acknowledgments   •  Eric  Franzosa   •  Chetanya  Pandya     •  KonstanWn  Voevodski   •  Jignesh  Parikh   •  Han  Hu     •  Yong  Wang   •  Jasmin  Coulombe-­‐HunWngton   •  Christopher  Jacobs   •  Bolan  Linghu     •  Sara  Garamszegi   •  Alexandra  Dumitriu   •  Ran  Xue   •  Qingyu  Gao   •  Sachit  Bakshi   •  Kevin  Lynagh   •  Javier  Pérez-­‐Florido         18   Funding  

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