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Open AccessArticle

Phylogenetic Weighting Does Little to Improve the Accuracy of Evolutionary Coupling Analyses

Department of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA
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Entropy 2019, 21(10), 1000; https://doi.org/10.3390/e21101000
Received: 14 August 2019 / Revised: 9 October 2019 / Accepted: 10 October 2019 / Published: 12 October 2019
Homologous sequence alignments contain important information about the constraints that shape protein family evolution. Correlated changes between different residues, for instance, can be highly predictive of physical contacts within three-dimensional structures. Detecting such co-evolutionary signals via direct coupling analysis is particularly challenging given the shared phylogenetic history and uneven sampling of different lineages from which protein sequences are derived. Current best practices for mitigating such effects include sequence-identity-based weighting of input sequences and post-hoc re-scaling of evolutionary coupling scores. However, numerous weighting schemes have been previously developed for other applications, and it is unknown whether any of these schemes may better account for phylogenetic artifacts in evolutionary coupling analyses. Here, we show across a dataset of 150 diverse protein families that the current best practices out-perform several alternative sequence- and tree-based weighting methods. Nevertheless, we find that sequence weighting in general provides only a minor benefit relative to post-hoc transformations that re-scale the derived evolutionary couplings. While our findings do not rule out the possibility that an as-yet-untested weighting method may show improved results, the similar predictive accuracies that we observe across conceptually distinct weighting methods suggests that there may be little room for further improvement on top of existing strategies. View Full-Text
Keywords: direct coupling analysis; evolutionary coupling analysis; contact prediction; phylogenetic bias direct coupling analysis; evolutionary coupling analysis; contact prediction; phylogenetic bias
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Hockenberry, A.J.; Wilke, C.O. Phylogenetic Weighting Does Little to Improve the Accuracy of Evolutionary Coupling Analyses. Entropy 2019, 21, 1000.

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