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Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation
Boolean networks have been widely used to model gene networks. However, such models are coarse-grained to an extent that they abstract away molecular specificities of gene regulation. Alternatively, bipartite Boolean network models of gene regulation explicitly distinguish genes from transcription f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616893/ https://www.ncbi.nlm.nih.gov/pubmed/36307465 http://dx.doi.org/10.1038/s41598-022-22654-7 |
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author | Yadav, Yasharth Subbaroyan, Ajay Martin, Olivier C. Samal, Areejit |
author_facet | Yadav, Yasharth Subbaroyan, Ajay Martin, Olivier C. Samal, Areejit |
author_sort | Yadav, Yasharth |
collection | PubMed |
description | Boolean networks have been widely used to model gene networks. However, such models are coarse-grained to an extent that they abstract away molecular specificities of gene regulation. Alternatively, bipartite Boolean network models of gene regulation explicitly distinguish genes from transcription factors (TFs). In such bipartite models, multiple TFs may simultaneously contribute to gene regulation by forming heteromeric complexes, thus giving rise to composition structures. Since bipartite Boolean models are relatively recent, an empirical investigation of their biological plausibility is lacking. Here, we estimate the prevalence of composition structures arising through heteromeric complexes. Moreover, we present an additional mechanism where composition structures may arise as a result of multiple TFs binding to cis-regulatory regions and provide empirical support for this mechanism. Next, we compare the restriction in BFs imposed by composition structures and by biologically meaningful properties. We find that though composition structures can severely restrict the number of Boolean functions (BFs) driving a gene, the two types of minimally complex BFs, namely nested canalyzing functions (NCFs) and read-once functions (RoFs), are comparatively more restrictive. Finally, we find that composition structures are highly enriched in real networks, but this enrichment most likely comes from NCFs and RoFs. |
format | Online Article Text |
id | pubmed-9616893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96168932022-10-30 Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation Yadav, Yasharth Subbaroyan, Ajay Martin, Olivier C. Samal, Areejit Sci Rep Article Boolean networks have been widely used to model gene networks. However, such models are coarse-grained to an extent that they abstract away molecular specificities of gene regulation. Alternatively, bipartite Boolean network models of gene regulation explicitly distinguish genes from transcription factors (TFs). In such bipartite models, multiple TFs may simultaneously contribute to gene regulation by forming heteromeric complexes, thus giving rise to composition structures. Since bipartite Boolean models are relatively recent, an empirical investigation of their biological plausibility is lacking. Here, we estimate the prevalence of composition structures arising through heteromeric complexes. Moreover, we present an additional mechanism where composition structures may arise as a result of multiple TFs binding to cis-regulatory regions and provide empirical support for this mechanism. Next, we compare the restriction in BFs imposed by composition structures and by biologically meaningful properties. We find that though composition structures can severely restrict the number of Boolean functions (BFs) driving a gene, the two types of minimally complex BFs, namely nested canalyzing functions (NCFs) and read-once functions (RoFs), are comparatively more restrictive. Finally, we find that composition structures are highly enriched in real networks, but this enrichment most likely comes from NCFs and RoFs. Nature Publishing Group UK 2022-10-28 /pmc/articles/PMC9616893/ /pubmed/36307465 http://dx.doi.org/10.1038/s41598-022-22654-7 Text en © The Author(s) 2022 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/) . |
spellingShingle | Article Yadav, Yasharth Subbaroyan, Ajay Martin, Olivier C. Samal, Areejit Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title | Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title_full | Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title_fullStr | Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title_full_unstemmed | Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title_short | Relative importance of composition structures and biologically meaningful logics in bipartite Boolean models of gene regulation |
title_sort | relative importance of composition structures and biologically meaningful logics in bipartite boolean models of gene regulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616893/ https://www.ncbi.nlm.nih.gov/pubmed/36307465 http://dx.doi.org/10.1038/s41598-022-22654-7 |
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