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[Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes

BACKGROUND: Upon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ([...

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Autores principales: Martinez-Seidel, Federico, Hsieh, Yin-Chen, Walther, Dirk, Kopka, Joachim, Pereira Firmino, Alexandre Augusto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686616/
https://www.ncbi.nlm.nih.gov/pubmed/34930116
http://dx.doi.org/10.1186/s12859-021-04510-z
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author Martinez-Seidel, Federico
Hsieh, Yin-Chen
Walther, Dirk
Kopka, Joachim
Pereira Firmino, Alexandre Augusto
author_facet Martinez-Seidel, Federico
Hsieh, Yin-Chen
Walther, Dirk
Kopka, Joachim
Pereira Firmino, Alexandre Augusto
author_sort Martinez-Seidel, Federico
collection PubMed
description BACKGROUND: Upon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ([Formula: see text] ), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specific conditions are spatially confined to particular regions within the large ribosomal complex. RESULTS: [Formula: see text] translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its first implementation, [Formula: see text] considers rProteins and ignores rRNA and other objects. Spatial regions are defined using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges reflecting the physical proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specific biological questions by yielding regions of different sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the [Formula: see text] workflow, considering that they yield different sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defined regions, available abundance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defined spatial regions. We applied [Formula: see text] to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translating polysomes are significantly constrained to a ribosomal region close to the tRNA entry and exit sites. CONCLUSIONS: [Formula: see text] offers a computational method to partition multi-protein complexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. [Formula: see text] is applicable to any multi-protein complex given appropriate structural and abundance-change data. [Formula: see text] is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04510-z.
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spelling pubmed-86866162021-12-20 [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes Martinez-Seidel, Federico Hsieh, Yin-Chen Walther, Dirk Kopka, Joachim Pereira Firmino, Alexandre Augusto BMC Bioinformatics Software BACKGROUND: Upon environmental stimuli, ribosomes are surmised to undergo compositional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter ([Formula: see text] ), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specific conditions are spatially confined to particular regions within the large ribosomal complex. RESULTS: [Formula: see text] translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its first implementation, [Formula: see text] considers rProteins and ignores rRNA and other objects. Spatial regions are defined using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges reflecting the physical proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specific biological questions by yielding regions of different sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the [Formula: see text] workflow, considering that they yield different sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defined regions, available abundance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defined spatial regions. We applied [Formula: see text] to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translating polysomes are significantly constrained to a ribosomal region close to the tRNA entry and exit sites. CONCLUSIONS: [Formula: see text] offers a computational method to partition multi-protein complexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. [Formula: see text] is applicable to any multi-protein complex given appropriate structural and abundance-change data. [Formula: see text] is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04510-z. BioMed Central 2021-12-20 /pmc/articles/PMC8686616/ /pubmed/34930116 http://dx.doi.org/10.1186/s12859-021-04510-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Software
Martinez-Seidel, Federico
Hsieh, Yin-Chen
Walther, Dirk
Kopka, Joachim
Pereira Firmino, Alexandre Augusto
[Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title_full [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title_fullStr [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title_full_unstemmed [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title_short [Formula: see text] : ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes
title_sort [formula: see text] : complexome-structural network interpreter used to study spatial enrichment in metazoan ribosomes
topic Software
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686616/
https://www.ncbi.nlm.nih.gov/pubmed/34930116
http://dx.doi.org/10.1186/s12859-021-04510-z
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