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  4. Correlations from structure and phylogeny combine constructively in the inference of protein partners from sequences
 
research article

Correlations from structure and phylogeny combine constructively in the inference of protein partners from sequences

Gerardos, Andonis
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Dietler, Nicola
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Bitbol, Anne-Florence  
May 1, 2022
Plos Computational Biology

Inferring protein-protein interactions from sequences is an important task in computational biology. Recent methods based on Direct Coupling Analysis (DCA) or Mutual Information (MI) allow to find interaction partners among paralogs of two protein families. Does successful inference mainly rely on correlations from structural contacts or from phylogeny, or both? Do these two types of signal combine constructively or hinder each other? To address these questions, we generate and analyze synthetic data produced using a minimal model that allows us to control the amounts of structural constraints and phylogeny. We show that correlations from these two sources combine constructively to increase the performance of partner inference by DCA or MI. Furthermore, signal from phylogeny can rescue partner inference when signal from contacts becomes less informative, including in the realistic case where inter-protein contacts are restricted to a small subset of sites. We also demonstrate that DCA-inferred couplings between non-contact pairs of sites improve partner inference in the presence of strong phylogeny, while deteriorating it otherwise. Moreover, restricting to non-contact pairs of sites preserves inference performance in the presence of strong phylogeny. In a natural data set, as well as in realistic synthetic data based on it, we find that non-contact pairs of sites contribute positively to partner inference performance, and that restricting to them preserves performance, evidencing an important role of phylogeny.

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Type
research article
DOI
10.1371/journal.pcbi.1010147
Web of Science ID

WOS:001084621500012

Author(s)
Gerardos, Andonis
Dietler, Nicola
Bitbol, Anne-Florence  
Date Issued

2022-05-01

Publisher

Public Library Science

Published in
Plos Computational Biology
Volume

18

Issue

5

Article Number

e1010147

Subjects

Life Sciences & Biomedicine

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Direct-Coupling Analysis

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Coevolution

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Information

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Evolution

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Contacts

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Reveals

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Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPBITBOL  
FunderGrant Number

European Research Council (ERC) under the European Union

851173

European Research Council (ERC)

851173

Available on Infoscience
February 16, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/203875
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