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COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome
- Source :
- Bioinformatics, 35(17), 3083-3091. Oxford University Press, Bioinformatics, Bioinformatics, 35, 3083-3091, Bioinformatics, 35, 17, pp. 3083-3091
- Publication Year :
- 2019
-
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 multi-dimensional 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 remodeling 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 (mitochondrial contact site and cristae organizing system, prohibitins), or are attached to it (the large ribosomal subunit). Availability and implementation COPAL is written in python and is available from http://github.com/cmbi/copal. Supplementary information Supplementary data are available at Bioinformatics online.
- Subjects :
- Statistics and Probability
Tafazzin
Computational biology
Mitochondrion
Biochemistry
Mass Spectrometry
Mitochondrial Proteins
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Large ribosomal subunit
ddc:570
Organelle
Cardiolipin
medicine
Humans
Inner mitochondrial membrane
Molecular Biology
Gene
030304 developmental biology
0303 health sciences
biology
Chemistry
Systems Biology
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Barth syndrome
medicine.disease
Original Papers
Computer Science Applications
Cell biology
Mitochondria
Computational Mathematics
Computational Theory and Mathematics
Barth Syndrome
Mutation
biology.protein
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 13674803
- Volume :
- 35
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Bioinformatics
- Accession number :
- edsair.doi.dedup.....8be5a4dcb0e356aecd9f854f05511a5a