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Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets

BACKGROUND: Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner. RESULTS: In this study we propose a novel statistic named AR-score (aver...

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Detalles Bibliográficos
Autores principales: Yang, Huan, Cheng, Chao, Zhang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212578/
https://www.ncbi.nlm.nih.gov/pubmed/22096597
http://dx.doi.org/10.1371/journal.pone.0027579
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author Yang, Huan
Cheng, Chao
Zhang, Wei
author_facet Yang, Huan
Cheng, Chao
Zhang, Wei
author_sort Yang, Huan
collection PubMed
description BACKGROUND: Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner. RESULTS: In this study we propose a novel statistic named AR-score (average rank based score) to measure pathway activities based on microarray gene expression profiles. We calculate and compare the AR-scores of pathways in microarray datasets containing expression profiles for a wide range of cancer types as well as the corresponding normal tissues. We find that many pathways undergo significant activity changes in tumors with respect to normal tissues. AR-scores for a small subset of pathways are capable of distinguishing tumor from normal tissues or classifying tumor subtypes. In normal tissues many pathways are highly correlated in their activities, whereas their correlations reduce significantly in tumors and cancer cell lines. The co-expression of genes in the same pathways was also significantly perturbed in tumors. CONCLUSIONS: The co-regulation of genes in the same pathways and co-regulation of different pathways are significantly perturbed in tumors versus normal tissues. Our method provides a useful tool for better understanding the mechanistic changes in tumors, which can also be used for exploring other biological problems.
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spelling pubmed-32125782011-11-17 Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets Yang, Huan Cheng, Chao Zhang, Wei PLoS One Research Article BACKGROUND: Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner. RESULTS: In this study we propose a novel statistic named AR-score (average rank based score) to measure pathway activities based on microarray gene expression profiles. We calculate and compare the AR-scores of pathways in microarray datasets containing expression profiles for a wide range of cancer types as well as the corresponding normal tissues. We find that many pathways undergo significant activity changes in tumors with respect to normal tissues. AR-scores for a small subset of pathways are capable of distinguishing tumor from normal tissues or classifying tumor subtypes. In normal tissues many pathways are highly correlated in their activities, whereas their correlations reduce significantly in tumors and cancer cell lines. The co-expression of genes in the same pathways was also significantly perturbed in tumors. CONCLUSIONS: The co-regulation of genes in the same pathways and co-regulation of different pathways are significantly perturbed in tumors versus normal tissues. Our method provides a useful tool for better understanding the mechanistic changes in tumors, which can also be used for exploring other biological problems. Public Library of Science 2011-11-09 /pmc/articles/PMC3212578/ /pubmed/22096597 http://dx.doi.org/10.1371/journal.pone.0027579 Text en Yang et al. 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
Yang, Huan
Cheng, Chao
Zhang, Wei
Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title_full Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title_fullStr Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title_full_unstemmed Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title_short Average Rank-Based Score to Measure Deregulation of Molecular Pathway Gene Sets
title_sort average rank-based score to measure deregulation of molecular pathway gene sets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212578/
https://www.ncbi.nlm.nih.gov/pubmed/22096597
http://dx.doi.org/10.1371/journal.pone.0027579
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