Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations

Cai, Xiaodong - Bazerque, Juan Andrés - Giannakis, Georgios B

Resumen:

Integrating genetic perturbations with gene expression data not only improves accuracy of regulatory network topology inference, but also enables learning of causal regulatory relations between genes. Although a number of methods have been developed to integrate both types of data, the desiderata of efficient and powerful algorithms still remains. In this paper, sparse structural equation models (SEMs) are employed to integrate both gene expression data and cis-expression quantitative trait loci (cis-eQTL), for modeling gene regulatory networks in accordance with biological evidence about genes regulating or being regulated by a small number of genes. A systematic inference method named sparsity-aware maximum likelihood (SML) is developed for SEM estimation. Using simulated directed acyclic or cyclic networks, the SML performance is compared with that of two state-of-the-art algorithms: the adaptive Lasso (AL) based scheme, and the QTL-directed dependency graph (QDG) method. Computer simulations demonstrate that the novel SML algorithm offers significantly better performance than the AL-based and QDG algorithms across all sample sizes from 100 to 1,000, in terms of detection power and false discovery rate, in all the cases tested that include acyclic or cyclic networks of 10, 30 and 300 genes. The SML method is further applied to infer a network of 39 human genes that are related to the immune function and are chosen to have a reliable eQTL per gene. The resulting network consists of 9 genes and 13 edges. Most of the edges represent interactions reasonably expected from experimental evidence, while the remaining may just indicate the emergence of new interactions. The sparse SEM and efficient SML algorithm provide an effective means of exploiting both gene expression and perturbation data to infer gene regulatory networks. An open-source computer program implementing the SML algorithm is freely available upon request


Detalles Bibliográficos
2013
Sistemas y Control
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/41817
https://doi.org/10.1371/journal.pcbi.1003068
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
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author Cai, Xiaodong
author2 Bazerque, Juan Andrés
Giannakis, Georgios B
author2_role author
author
author_facet Cai, Xiaodong
Bazerque, Juan Andrés
Giannakis, Georgios B
author_role author
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dc.creator.none.fl_str_mv Cai, Xiaodong
Bazerque, Juan Andrés
Giannakis, Georgios B
dc.date.accessioned.none.fl_str_mv 2023-12-11T19:57:54Z
dc.date.available.none.fl_str_mv 2023-12-11T19:57:54Z
dc.date.issued.es.fl_str_mv 2013
dc.date.submitted.es.fl_str_mv 20231211
dc.description.abstract.none.fl_txt_mv Integrating genetic perturbations with gene expression data not only improves accuracy of regulatory network topology inference, but also enables learning of causal regulatory relations between genes. Although a number of methods have been developed to integrate both types of data, the desiderata of efficient and powerful algorithms still remains. In this paper, sparse structural equation models (SEMs) are employed to integrate both gene expression data and cis-expression quantitative trait loci (cis-eQTL), for modeling gene regulatory networks in accordance with biological evidence about genes regulating or being regulated by a small number of genes. A systematic inference method named sparsity-aware maximum likelihood (SML) is developed for SEM estimation. Using simulated directed acyclic or cyclic networks, the SML performance is compared with that of two state-of-the-art algorithms: the adaptive Lasso (AL) based scheme, and the QTL-directed dependency graph (QDG) method. Computer simulations demonstrate that the novel SML algorithm offers significantly better performance than the AL-based and QDG algorithms across all sample sizes from 100 to 1,000, in terms of detection power and false discovery rate, in all the cases tested that include acyclic or cyclic networks of 10, 30 and 300 genes. The SML method is further applied to infer a network of 39 human genes that are related to the immune function and are chosen to have a reliable eQTL per gene. The resulting network consists of 9 genes and 13 edges. Most of the edges represent interactions reasonably expected from experimental evidence, while the remaining may just indicate the emergence of new interactions. The sparse SEM and efficient SML algorithm provide an effective means of exploiting both gene expression and perturbation data to infer gene regulatory networks. An open-source computer program implementing the SML algorithm is freely available upon request
dc.identifier.citation.es.fl_str_mv Cai X, Bazerque JA, Giannakis GB "Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations”. PLoS Computational Biology, 2013, v.9, no.5, e1003068. https://doi.org/10.1371/journal.pcbi.1003068
dc.identifier.doi.es.fl_str_mv https://doi.org/10.1371/journal.pcbi.1003068
dc.identifier.eissn.es.fl_str_mv 1553-7358
dc.identifier.issn.es.fl_str_mv 1553-734X
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/41817
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv Public Library of Science
dc.relation.ispartof.es.fl_str_mv PLoS Computational Biology, 2013, v.9, no.5
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.other.es.fl_str_mv Sistemas y Control
dc.title.none.fl_str_mv Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description Integrating genetic perturbations with gene expression data not only improves accuracy of regulatory network topology inference, but also enables learning of causal regulatory relations between genes. Although a number of methods have been developed to integrate both types of data, the desiderata of efficient and powerful algorithms still remains. In this paper, sparse structural equation models (SEMs) are employed to integrate both gene expression data and cis-expression quantitative trait loci (cis-eQTL), for modeling gene regulatory networks in accordance with biological evidence about genes regulating or being regulated by a small number of genes. A systematic inference method named sparsity-aware maximum likelihood (SML) is developed for SEM estimation. Using simulated directed acyclic or cyclic networks, the SML performance is compared with that of two state-of-the-art algorithms: the adaptive Lasso (AL) based scheme, and the QTL-directed dependency graph (QDG) method. Computer simulations demonstrate that the novel SML algorithm offers significantly better performance than the AL-based and QDG algorithms across all sample sizes from 100 to 1,000, in terms of detection power and false discovery rate, in all the cases tested that include acyclic or cyclic networks of 10, 30 and 300 genes. The SML method is further applied to infer a network of 39 human genes that are related to the immune function and are chosen to have a reliable eQTL per gene. The resulting network consists of 9 genes and 13 edges. Most of the edges represent interactions reasonably expected from experimental evidence, while the remaining may just indicate the emergence of new interactions. The sparse SEM and efficient SML algorithm provide an effective means of exploiting both gene expression and perturbation data to infer gene regulatory networks. An open-source computer program implementing the SML algorithm is freely available upon request
eu_rights_str_mv openAccess
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identifier_str_mv Cai X, Bazerque JA, Giannakis GB "Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations”. PLoS Computational Biology, 2013, v.9, no.5, e1003068. https://doi.org/10.1371/journal.pcbi.1003068
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publishDate 2013
reponame_str COLIBRI
repository.mail.fl_str_mv mabel.seroubian@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
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rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling 2023-12-11T19:57:54Z2023-12-11T19:57:54Z201320231211Cai X, Bazerque JA, Giannakis GB "Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations”. PLoS Computational Biology, 2013, v.9, no.5, e1003068. https://doi.org/10.1371/journal.pcbi.10030681553-734Xhttps://hdl.handle.net/20.500.12008/41817https://doi.org/10.1371/journal.pcbi.10030681553-7358Integrating genetic perturbations with gene expression data not only improves accuracy of regulatory network topology inference, but also enables learning of causal regulatory relations between genes. Although a number of methods have been developed to integrate both types of data, the desiderata of efficient and powerful algorithms still remains. In this paper, sparse structural equation models (SEMs) are employed to integrate both gene expression data and cis-expression quantitative trait loci (cis-eQTL), for modeling gene regulatory networks in accordance with biological evidence about genes regulating or being regulated by a small number of genes. A systematic inference method named sparsity-aware maximum likelihood (SML) is developed for SEM estimation. Using simulated directed acyclic or cyclic networks, the SML performance is compared with that of two state-of-the-art algorithms: the adaptive Lasso (AL) based scheme, and the QTL-directed dependency graph (QDG) method. Computer simulations demonstrate that the novel SML algorithm offers significantly better performance than the AL-based and QDG algorithms across all sample sizes from 100 to 1,000, in terms of detection power and false discovery rate, in all the cases tested that include acyclic or cyclic networks of 10, 30 and 300 genes. The SML method is further applied to infer a network of 39 human genes that are related to the immune function and are chosen to have a reliable eQTL per gene. The resulting network consists of 9 genes and 13 edges. Most of the edges represent interactions reasonably expected from experimental evidence, while the remaining may just indicate the emergence of new interactions. The sparse SEM and efficient SML algorithm provide an effective means of exploiting both gene expression and perturbation data to infer gene regulatory networks. An open-source computer program implementing the SML algorithm is freely available upon requestMade available in DSpace on 2023-12-11T19:57:54Z (GMT). No. of bitstreams: 5 CBG13.pdf: 410390 bytes, checksum: 012d6a16ab6e2f4785e838c6eba4384b (MD5) license_text: 21936 bytes, checksum: 9833653f73f7853880c94a6fead477b1 (MD5) license_url: 49 bytes, checksum: 4afdbb8c545fd630ea7db775da747b2f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) license.txt: 4244 bytes, checksum: 528b6a3c8c7d0c6e28129d576e989607 (MD5) Previous issue date: 2013enengPublic Library of SciencePLoS Computational Biology, 2013, v.9, no.5Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad De La República. (Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)Sistemas y ControlInference of gene regulatory networks with sparse structural equation models exploiting genetic perturbationsArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaCai, XiaodongBazerque, Juan AndrésGiannakis, Georgios 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- Universidad de la Repúblicafalse
spellingShingle Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
Cai, Xiaodong
Sistemas y Control
status_str publishedVersion
title Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
title_full Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
title_fullStr Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
title_full_unstemmed Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
title_short Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
title_sort Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations
topic Sistemas y Control
url https://hdl.handle.net/20.500.12008/41817
https://doi.org/10.1371/journal.pcbi.1003068