A fast and automated solution for accurately resolving protein domain architectures

Bioinformatics
Corin YeatsChristine Orengo

Abstract

Accurate prediction of the domain content and arrangement in multi-domain proteins (which make up >65% of the large-scale protein databases) provides a valuable tool for function prediction, comparative genomics and studies of molecular evolution. However, scanning a multi-domain protein against a database of domain sequence profiles can often produce conflicting and overlapping matches. We have developed a novel method that employs heaviest weighted clique-finding (HCF), which we show significantly outperforms standard published approaches based on successively assigning the best non-overlapping match (Best Match Cascade, BMC). We created benchmark data set of structural domain assignments in the CATH database and a corresponding set of Hidden Markov Model-based domain predictions. Using these, we demonstrate that by considering all possible combinations of matches using the HCF approach, we achieve much higher prediction accuracy than the standard BMC method. We also show that it is essential to allow overlapping domain matches to a query in order to identify correct domain assignments. Furthermore, we introduce a straightforward and effective protocol for resolving any overlapping assignments, and producing a single set of n...Continue Reading

References

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Citations

Feb 8, 2011·PLoS Computational Biology·Iain MelvinChristina Leslie
Mar 27, 2013·Annual Review of Biophysics·Rachel KolodnyMichael Levitt
Jun 27, 2013·BMC Genomics·Xin-Chao WangYa-Jun Yang
Nov 26, 2013·Nucleic Acids Research·Jonathan G LeesChristine A Orengo
Feb 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ramya Purkanti, Mukund Thattai
Oct 6, 2015·Methods : a Companion to Methods in Enzymology·Sayoni Das, Christine A Orengo
May 13, 2015·Nucleic Acids Research·Sayoni DasChristine A Orengo
Mar 27, 2013·BMC Bioinformatics·Robert Rentzsch, Christine A Orengo
Nov 18, 2015·PLoS Computational Biology·Alejandro OchoaMona Singh
Apr 14, 2017·Bioinformatics·Alejandro Ochoa, Mona Singh
Nov 8, 2017·Nucleic Acids Research·Tony E LewisJonathan Lees
Jun 20, 2015·Current Protocols in Bioinformatics·Ian SillitoeChristine Orengo
Jul 17, 2019·Nature Chemical Biology·Eric J N HelfrichJörn Piel
Jun 9, 2017·Malaria Journal·Juliana BernardesAlessandra Carbone
Mar 3, 2021·PLoS Computational Biology·Su Datt LamChristine A Orengo
Jun 3, 2021·GigaScience·Pedro QueirósPaul Wilmes

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