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Characterizing the Network of Drugs and Their Affected Metabolic Subpathways
A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480395/ https://www.ncbi.nlm.nih.gov/pubmed/23112813 http://dx.doi.org/10.1371/journal.pone.0047326 |
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author | Li, Chunquan Shang, Desi Wang, Yan Li, Jing Han, Junwei Wang, Shuyuan Yao, Qianlan Wang, Yingying Zhang, Yunpeng Zhang, Chunlong Xu, Yanjun Jiang, Wei Li, Xia |
author_facet | Li, Chunquan Shang, Desi Wang, Yan Li, Jing Han, Junwei Wang, Shuyuan Yao, Qianlan Wang, Yingying Zhang, Yunpeng Zhang, Chunlong Xu, Yanjun Jiang, Wei Li, Xia |
author_sort | Li, Chunquan |
collection | PubMed |
description | A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. |
format | Online Article Text |
id | pubmed-3480395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34803952012-10-30 Characterizing the Network of Drugs and Their Affected Metabolic Subpathways Li, Chunquan Shang, Desi Wang, Yan Li, Jing Han, Junwei Wang, Shuyuan Yao, Qianlan Wang, Yingying Zhang, Yunpeng Zhang, Chunlong Xu, Yanjun Jiang, Wei Li, Xia PLoS One Research Article A fundamental issue in biology and medicine is illustration of the overall drug impact which is always the consequence of changes in local regions of metabolic pathways (subpathways). To gain insights into the global relationship between drugs and their affected metabolic subpathways, we constructed a drug–metabolic subpathway network (DRSN). This network included 3925 significant drug–metabolic subpathway associations representing drug dual effects. Through analyses based on network biology, we found that if drugs were linked to the same subpathways in the DRSN, they tended to share the same indications and side effects. Furthermore, if drugs shared more subpathways, they tended to share more side effects. We then calculated the association score by integrating drug-affected subpathways and disease-related subpathways to quantify the extent of the associations between each drug class and disease class. The results showed some close drug–disease associations such as sex hormone drugs and cancer suggesting drug dual effects. Surprisingly, most drugs displayed close associations with their side effects rather than their indications. To further investigate the mechanism of drug dual effects, we classified all the subpathways in the DRSN into therapeutic and non-therapeutic subpathways representing drug therapeutic effects and side effects. Compared to drug side effects, the therapeutic effects tended to work through tissue-specific genes and these genes tend to be expressed in the adrenal gland, liver and kidney; while drug side effects always occurred in the liver, bone marrow and trachea. Taken together, the DRSN could provide great insights into understanding the global relationship between drugs and metabolic subpathways. Public Library of Science 2012-10-24 /pmc/articles/PMC3480395/ /pubmed/23112813 http://dx.doi.org/10.1371/journal.pone.0047326 Text en © 2012 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, Chunquan Shang, Desi Wang, Yan Li, Jing Han, Junwei Wang, Shuyuan Yao, Qianlan Wang, Yingying Zhang, Yunpeng Zhang, Chunlong Xu, Yanjun Jiang, Wei Li, Xia Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title | Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title_full | Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title_fullStr | Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title_full_unstemmed | Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title_short | Characterizing the Network of Drugs and Their Affected Metabolic Subpathways |
title_sort | characterizing the network of drugs and their affected metabolic subpathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480395/ https://www.ncbi.nlm.nih.gov/pubmed/23112813 http://dx.doi.org/10.1371/journal.pone.0047326 |
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