Weighted frequent gene co-expression network mining to identify genes involved in genome stability.

Gene co-expression network analysis is an effective method for predicting gene functions and disease biomarkers. However, few studies have systematically identified co-expressed genes involved in the molecular origin and development of various types of tumors. In this study, we used a network mining...

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Main Authors: Jie Zhang, Kewei Lu, Yang Xiang, Muhtadi Islam, Shweta Kotian, Zeina Kais, Cindy Lee, Mansi Arora, Hui-Wen Liu, Jeffrey D Parvin, Kun Huang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC3431293?pdf=render
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author Jie Zhang
Kewei Lu
Yang Xiang
Muhtadi Islam
Shweta Kotian
Zeina Kais
Cindy Lee
Mansi Arora
Hui-Wen Liu
Jeffrey D Parvin
Kun Huang
author_facet Jie Zhang
Kewei Lu
Yang Xiang
Muhtadi Islam
Shweta Kotian
Zeina Kais
Cindy Lee
Mansi Arora
Hui-Wen Liu
Jeffrey D Parvin
Kun Huang
author_sort Jie Zhang
collection DOAJ
description Gene co-expression network analysis is an effective method for predicting gene functions and disease biomarkers. However, few studies have systematically identified co-expressed genes involved in the molecular origin and development of various types of tumors. In this study, we used a network mining algorithm to identify tightly connected gene co-expression networks that are frequently present in microarray datasets from 33 types of cancer which were derived from 16 organs/tissues. We compared the results with networks found in multiple normal tissue types and discovered 18 tightly connected frequent networks in cancers, with highly enriched functions on cancer-related activities. Most networks identified also formed physically interacting networks. In contrast, only 6 networks were found in normal tissues, which were highly enriched for housekeeping functions. The largest cancer network contained many genes with genome stability maintenance functions. We tested 13 selected genes from this network for their involvement in genome maintenance using two cell-based assays. Among them, 10 were shown to be involved in either homology-directed DNA repair or centrosome duplication control including the well-known cancer marker MKI67. Our results suggest that the commonly recognized characteristics of cancers are supported by highly coordinated transcriptomic activities. This study also demonstrated that the co-expression network directed approach provides a powerful tool for understanding cancer physiology, predicting new gene functions, as well as providing new target candidates for cancer therapeutics.
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spelling doaj.art-8e538ade19134298862ed292dd2f3ec72022-12-21T19:08:44ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-0188e100265610.1371/journal.pcbi.1002656Weighted frequent gene co-expression network mining to identify genes involved in genome stability.Jie ZhangKewei LuYang XiangMuhtadi IslamShweta KotianZeina KaisCindy LeeMansi AroraHui-Wen LiuJeffrey D ParvinKun HuangGene co-expression network analysis is an effective method for predicting gene functions and disease biomarkers. However, few studies have systematically identified co-expressed genes involved in the molecular origin and development of various types of tumors. In this study, we used a network mining algorithm to identify tightly connected gene co-expression networks that are frequently present in microarray datasets from 33 types of cancer which were derived from 16 organs/tissues. We compared the results with networks found in multiple normal tissue types and discovered 18 tightly connected frequent networks in cancers, with highly enriched functions on cancer-related activities. Most networks identified also formed physically interacting networks. In contrast, only 6 networks were found in normal tissues, which were highly enriched for housekeeping functions. The largest cancer network contained many genes with genome stability maintenance functions. We tested 13 selected genes from this network for their involvement in genome maintenance using two cell-based assays. Among them, 10 were shown to be involved in either homology-directed DNA repair or centrosome duplication control including the well-known cancer marker MKI67. Our results suggest that the commonly recognized characteristics of cancers are supported by highly coordinated transcriptomic activities. This study also demonstrated that the co-expression network directed approach provides a powerful tool for understanding cancer physiology, predicting new gene functions, as well as providing new target candidates for cancer therapeutics.http://europepmc.org/articles/PMC3431293?pdf=render
spellingShingle Jie Zhang
Kewei Lu
Yang Xiang
Muhtadi Islam
Shweta Kotian
Zeina Kais
Cindy Lee
Mansi Arora
Hui-Wen Liu
Jeffrey D Parvin
Kun Huang
Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
PLoS Computational Biology
title Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
title_full Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
title_fullStr Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
title_full_unstemmed Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
title_short Weighted frequent gene co-expression network mining to identify genes involved in genome stability.
title_sort weighted frequent gene co expression network mining to identify genes involved in genome stability
url http://europepmc.org/articles/PMC3431293?pdf=render
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