netbiosig2014-talk by yu xia
DESCRIPTION
NetBioSIG2014 at ISMB in Boston, MA, USA on July 11, 2014TRANSCRIPT
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
Between-‐species systems biology
HH
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V H HumanProtein
VirusProtein
SequenceHomology
KnownInteraction
StableComplex
V HH
HHV
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HV
(a) (b) (c)
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• Within-‐human PPI network: endogenous • Human-‐virus PPI network: exogenous
2 [Uetz, 2006; Calderwood, 2007; Dyer, 2008; etc.]
Between-‐species structural systems biology
HH
H
H
H
H
H
H
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V H HumanProtein
VirusProtein
SequenceHomology
KnownInteraction
StableComplex
V HH
HHV
HH
HV
(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]
Within-‐human and human-‐virus structural interac6on networks
53 exogenous interac6ons 3,039 endogenous interac6ons
4
[Franzosa and Xia, PNAS 2011]
Virus proteins tend to bind to exis6ng endogenous interfaces
[Franzosa and Xia, PNAS 2011] 5
H H
V
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
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H H
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[Franzosa and Xia, PNAS 2011]
Viral binding accelerates endogenous interface evolu6on
[Franzosa and Xia, PNAS 2011] 7
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Two types of protein-‐protein interac6ons
Domain-‐domain interac6on Domain-‐mo6f interac6on
9
Case studies
[Davey, Travé, Gibson, Trends Biochem Sci 2011]
10
A domain-‐resolved map of human-‐human and human-‐virus protein-‐protein interac6on networks
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
11
Domain-‐resolved interac6ons are of high quality
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
12
Binding site mimicry evolves differently in virus and human proteins
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
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Viral proteins tend to target human proteins containing linear mo6f-‐binding (LMB) domains
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
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Viruses tend to target human proteins containing LMB domains, independent of host protein degree
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
15
Viral proteins have a higher frac6on of domain-‐mo6f interac6ons than human proteins
[Garamszegi, Franzosa, Xia, PLoS Pathogens 2013]
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
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
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