Comparative Clustering (CompaCt) of eukaryote complexomes identifies novel interactions and sheds light on protein complex evolution.

Autor: van Strien J; Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands., Evers F; Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Lutikurti M; Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands., Berendsen SL; Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands., Garanto A; Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Radboud Center for Mitochondrial Medicine (RCMM), Radboud University Medical Center, Nijmegen, the Netherlands., van Gemert GJ; Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Cabrera-Orefice A; Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands., Rodenburg RJ; Radboud Center for Mitochondrial Medicine (RCMM), Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Pediatrics, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands., Brandt U; Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.; Radboud Center for Mitochondrial Medicine (RCMM), Radboud University Medical Center, Nijmegen, the Netherlands.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Kooij TWA; Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Huynen MA; Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2023 Aug 07; Vol. 19 (8), pp. e1011090. Date of Electronic Publication: 2023 Aug 07 (Print Publication: 2023).
DOI: 10.1371/journal.pcbi.1011090
Abstrakt: Complexome profiling allows large-scale, untargeted, and comprehensive characterization of protein complexes in a biological sample using a combined approach of separating intact protein complexes e.g., by native gel electrophoresis, followed by mass spectrometric analysis of the proteins in the resulting fractions. Over the last decade, its application has resulted in a large collection of complexome profiling datasets. While computational methods have been developed for the analysis of individual datasets, methods for large-scale comparative analysis of complexomes from multiple species are lacking. Here, we present Comparative Clustering (CompaCt), that performs fully automated integrative analysis of complexome profiling data from multiple species, enabling systematic characterization and comparison of complexomes. CompaCt implements a novel method for leveraging orthology in comparative analysis to allow systematic identification of conserved as well as taxon-specific elements of the analyzed complexomes. We applied this method to a collection of 53 complexome profiles spanning the major branches of the eukaryotes. We demonstrate the ability of CompaCt to robustly identify the composition of protein complexes, and show that integrated analysis of multiple datasets improves characterization of complexes from specific complexome profiles when compared to separate analyses. We identified novel candidate interactors and complexes in a number of species from previously analyzed datasets, like the emp24, the V-ATPase and mitochondrial ATP synthase complexes. Lastly, we demonstrate the utility of CompaCt for the automated large-scale characterization of the complexome of the mosquito Anopheles stephensi shedding light on the evolution of metazoan protein complexes. CompaCt is available from https://github.com/cmbi/compact-bio.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 van Strien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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