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COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome
Open accessPreprint — published as 10.1093/bioinformatics/btz025 · Paper page
Abstract
Motivation: Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variations caused by that mutation. Results: We have developed the COmplexome Profiling ALignment (COPAL) tool that aligns multiple complexome profiles with each other. It includes the abundance profiles of all proteins on two gels, using a multidimensional implementation of the dynamic time warping algorithm to align the gels. Subsequent progressive alignment allows us to align multiple profiles with each other. We tested COPAL on complexome profiles from control mitochondria and from Barth syndrome (BTHS) mitochondria, which have a mutation in tafazzin gene that is involved in remodelling the inner mitochondrial membrane phospholipid cardiolipin. By comparing the variation between BTHS mitochondria and controls with the variation among either, we assessed the effects of BTHS on the abundance profiles of individual proteins. Combining those profiles with gene set enrichment analysis allows detecting significantly affected protein complexes. Most of the significantly affected protein complexes are located in the inner mitochondrial membrane (MICOS, prohibitins), or are attached to it (the large ribosomal subunit). Availability and implementation: COPAL is written in Python and is available from gttp://github.com/cmbi/copal . Contact: huynen@cmbi.ru.nl
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Metadata
- Authors
- Strien, J. V., Guerrero-Castillo, S., Chatzispyrou, I. A., Houtkooper, R. H., Brandt, U., & Huynen, M. A.
- Affiliations
- Amsterdam University Medical Centers (NL)
- Goethe University Frankfurt (DE)
- Radboud University Nijmegen (NL)
- Corresponding author
- Huynen, Martijn A.
- Venue
- Bioinformatics
- Publisher
- openRxiv
- Published
- 2018-09-12
- Volume
- 35
- Issue
- 17
- Pages
- 3083-3091
- ISSN
- 1367-4803 (ISSN-L)
- PMC
- PMC6735710
- OpenAlex
- W2949088611
- Cited by
- 42
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 2 · 2021: 12 · 2020: 6 · 2019: 3
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Bioinformatics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- ZonMw (91217009)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- complexome profiling, Barth syndrome, mitochondrial protein complexes, tafazzin, cardiolipin remodeling, inner mitochondrial membrane, copal, dynamic time warping, prohibitin, large ribosomal subunit
- MeSH terms
- Humans, Mitochondria, Mutation, Mass Spectrometry, Mitochondrial Proteins, Barth Syndrome
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