Combining phylogeny and coevolution improves the inference of interaction partners among paralogous proteins

PLoS Comput Biol. 2023 Mar 30;19(3):e1011010. doi: 10.1371/journal.pcbi.1011010. eCollection 2023 Mar.

Abstract

Predicting protein-protein interactions from sequences is an important goal of computational biology. Various sources of information can be used to this end. Starting from the sequences of two interacting protein families, one can use phylogeny or residue coevolution to infer which paralogs are specific interaction partners within each species. We show that these two signals can be combined to improve the performance of the inference of interaction partners among paralogs. For this, we first align the sequence-similarity graphs of the two families through simulated annealing, yielding a robust partial pairing. We next use this partial pairing to seed a coevolution-based iterative pairing algorithm. This combined method improves performance over either separate method. The improvement obtained is striking in the difficult cases where the average number of paralogs per species is large or where the total number of sequences is modest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Computational Biology / methods
  • Phylogeny
  • Protein Binding
  • Proteins* / chemistry

Substances

  • Proteins

Grants and funding

CAGP and MW acknowledge funding by the EU H2020 Research and Innovation Programme MSCA-RISE-2016 (grant agreement No. 734439 InferNet). AFB acknowledges funding by the European Research Council (ERC) under the EU H2020 Research and Innovation Programme (grant agreement No. 851173). AFB and MW thank the Institut de Biologie Paris-Seine (IBPS) at Sorbonne Université for funding via a Collaborative Grant (Action Incitative). This work was performed in part at the Aspen Center for Physics, which is supported by National Science Foundation grant PHY-1607611. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.