![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.]](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
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NetBioSIG2014-Talk by Yu Xia
- 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. 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. 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. Within-‐human and human-‐virus structural interac6on networks 53 exogenous interac6ons 3,039 endogenous interac6ons 4 [Franzosa and Xia, PNAS 2011]
- 5. Virus proteins tend to bind to exis6ng endogenous interfaces [Franzosa and Xia, PNAS 2011] 5 H H V
- 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. Viral binding accelerates endogenous interface evolu6on [Franzosa and Xia, PNAS 2011] 7
- 8. 8 Two types of protein-‐protein interac6ons Domain-‐domain interac6on Domain-‐mo6f interac6on
- 9. 9 Case studies [Davey, Travé, Gibson, Trends Biochem Sci 2011]
- 10. 10 A domain-‐resolved map of human-‐human and human-‐virus protein-‐protein interac6on networks [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 11. 11 Domain-‐resolved interac6ons are of high quality [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 12. 12 Binding site mimicry evolves differently in virus and human proteins [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 13. 13 Viral proteins tend to target human proteins containing linear mo6f-‐binding (LMB) domains [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 14. 14 Viruses tend to target human proteins containing LMB domains, independent of host protein degree [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 15. 15 Viral proteins have a higher frac6on of domain-‐mo6f interac6ons than human proteins [Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
- 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. 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. 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