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The Implications of Relationships between Human Diseases and Metabolic Subpathways

One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the “k-clique” subpathway identification method to...

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Autores principales: Li, Xia, Li, Chunquan, Shang, Desi, Li, Jing, Han, Junwei, Miao, Yingbo, Wang, Yan, Wang, Qianghu, Li, Wei, Wu, Chao, Zhang, Yunpeng, Li, Xiang, Yao, Qianlan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117879/
https://www.ncbi.nlm.nih.gov/pubmed/21695054
http://dx.doi.org/10.1371/journal.pone.0021131
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author Li, Xia
Li, Chunquan
Shang, Desi
Li, Jing
Han, Junwei
Miao, Yingbo
Wang, Yan
Wang, Qianghu
Li, Wei
Wu, Chao
Zhang, Yunpeng
Li, Xiang
Yao, Qianlan
author_facet Li, Xia
Li, Chunquan
Shang, Desi
Li, Jing
Han, Junwei
Miao, Yingbo
Wang, Yan
Wang, Qianghu
Li, Wei
Wu, Chao
Zhang, Yunpeng
Li, Xiang
Yao, Qianlan
author_sort Li, Xia
collection PubMed
description One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the “k-clique” subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly differential roles on the diversity of diseases caused by the corresponding subpathway.
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spelling pubmed-31178792011-06-21 The Implications of Relationships between Human Diseases and Metabolic Subpathways Li, Xia Li, Chunquan Shang, Desi Li, Jing Han, Junwei Miao, Yingbo Wang, Yan Wang, Qianghu Li, Wei Wu, Chao Zhang, Yunpeng Li, Xiang Yao, Qianlan PLoS One Research Article One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the “k-clique” subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly differential roles on the diversity of diseases caused by the corresponding subpathway. Public Library of Science 2011-06-17 /pmc/articles/PMC3117879/ /pubmed/21695054 http://dx.doi.org/10.1371/journal.pone.0021131 Text en Li 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
Li, Xia
Li, Chunquan
Shang, Desi
Li, Jing
Han, Junwei
Miao, Yingbo
Wang, Yan
Wang, Qianghu
Li, Wei
Wu, Chao
Zhang, Yunpeng
Li, Xiang
Yao, Qianlan
The Implications of Relationships between Human Diseases and Metabolic Subpathways
title The Implications of Relationships between Human Diseases and Metabolic Subpathways
title_full The Implications of Relationships between Human Diseases and Metabolic Subpathways
title_fullStr The Implications of Relationships between Human Diseases and Metabolic Subpathways
title_full_unstemmed The Implications of Relationships between Human Diseases and Metabolic Subpathways
title_short The Implications of Relationships between Human Diseases and Metabolic Subpathways
title_sort implications of relationships between human diseases and metabolic subpathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117879/
https://www.ncbi.nlm.nih.gov/pubmed/21695054
http://dx.doi.org/10.1371/journal.pone.0021131
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