Cargando…

A Computational Approach to Identifying Gene-microRNA Modules in Cancer

MicroRNAs (miRNAs) play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patient...

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Daeyong, Lee, Hyunju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303261/
https://www.ncbi.nlm.nih.gov/pubmed/25611546
http://dx.doi.org/10.1371/journal.pcbi.1004042
_version_ 1782353913707495424
author Jin, Daeyong
Lee, Hyunju
author_facet Jin, Daeyong
Lee, Hyunju
author_sort Jin, Daeyong
collection PubMed
description MicroRNAs (miRNAs) play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM) data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM.
format Online
Article
Text
id pubmed-4303261
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-43032612015-01-30 A Computational Approach to Identifying Gene-microRNA Modules in Cancer Jin, Daeyong Lee, Hyunju PLoS Comput Biol Research Article MicroRNAs (miRNAs) play key roles in the initiation and progression of various cancers by regulating genes. Regulatory interactions between genes and miRNAs are complex, as multiple miRNAs can regulate multiple genes. In addtion, these interactions vary from patient to patient and even among patients with the same cancer type, as cancer development is a heterogeneous process. These relationships are more complicated because transcription factors and other regulatory molecules can also regulate miRNAs and genes. Hence, it is important to identify the complex relationships between genes and miRNAs in cancer. In this study, we propose a computational approach to constructing modules that represent these relationships by integrating the expression data of genes and miRNAs with gene-gene interaction data. First, we used a biclustering algorithm to construct modules consisting of a subset of genes and a subset of samples to incorporate the heterogeneity of cancer cells. Second, we combined gene-gene interactions to include genes that play important roles in cancer-related pathways. Then, we selected miRNAs that are closely associated with genes in the modules based on a Gaussian Bayesian network and Bayesian Information Criteria. When we applied our approach to ovarian cancer and glioblastoma (GBM) data sets, 33 and 54 modules were constructed, respectively. In these modules, 91% and 94% of ovarian cancer and GBM modules, respectively, were explained either by direct regulation between genes and miRNAs or by indirect relationships via transcription factors. In addition, 48.4% and 74.0% of modules from ovarian cancer and GBM, respectively, were enriched with cancer-related pathways, and 51.7% and 71.7% of miRNAs in modules were ovarian cancer-related miRNAs and GBM-related miRNAs, respectively. Finally, we extensively analyzed significant modules and showed that most genes in these modules were related to ovarian cancer and GBM. Public Library of Science 2015-01-22 /pmc/articles/PMC4303261/ /pubmed/25611546 http://dx.doi.org/10.1371/journal.pcbi.1004042 Text en © 2015 Jin, Lee http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jin, Daeyong
Lee, Hyunju
A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title_full A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title_fullStr A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title_full_unstemmed A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title_short A Computational Approach to Identifying Gene-microRNA Modules in Cancer
title_sort computational approach to identifying gene-microrna modules in cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303261/
https://www.ncbi.nlm.nih.gov/pubmed/25611546
http://dx.doi.org/10.1371/journal.pcbi.1004042
work_keys_str_mv AT jindaeyong acomputationalapproachtoidentifyinggenemicrornamodulesincancer
AT leehyunju acomputationalapproachtoidentifyinggenemicrornamodulesincancer
AT jindaeyong computationalapproachtoidentifyinggenemicrornamodulesincancer
AT leehyunju computationalapproachtoidentifyinggenemicrornamodulesincancer