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The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study.

Davis AP, Murphy CG, Rosenstein MC, Wiegers TC, Mattingly CJ - BMC Med Genomics (2008)

Bottom Line: Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases.The analysis reported here is extensible to any environmental chemical or therapeutic drug.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioinformatics, The Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672 USA. apd@mdibl.org

ABSTRACT

Background: The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate physiological processes. Understanding interactions between environmental chemicals and genes/proteins may provide insights into the mechanisms of chemical actions, disease susceptibility, toxicity, and therapeutic drug interactions. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) provides these insights by curating and integrating data describing relationships between chemicals, genes/proteins, and human diseases. To illustrate the scope and application of CTD, we present an analysis of curated data for the chemical arsenic. Arsenic represents a major global environmental health threat and is associated with many diseases. The mechanisms by which arsenic modulates these diseases are not well understood.

Methods: Curated interactions between arsenic compounds and genes were downloaded using export and batch query tools at CTD. The list of genes was analyzed for molecular interactions, Gene Ontology (GO) terms, KEGG pathway annotations, and inferred disease relationships.

Results: CTD contains curated data from the published literature describing 2,738 molecular interactions between 21 different arsenic compounds and 1,456 genes and proteins. Analysis of these genes and proteins provide insight into the biological functions and molecular networks that are affected by exposure to arsenic, including stress response, apoptosis, cell cycle, and specific protein signaling pathways. Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.

Conclusion: CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases. While many reports describe the molecular response to arsenic, CTD integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug.

No MeSH data available.


Related in: MedlinePlus

Arsenic-gene-disease predictions. CTD describes a molecular interaction between arsenic (As) and 1,456 genes; 424 of those genes are also directly associated with a disease. The integration of these two data sets predicts diseases that parallel those already known to be associated with arsenic exposure, underscoring the potential value and validity of these inferred relationships.
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Figure 3: Arsenic-gene-disease predictions. CTD describes a molecular interaction between arsenic (As) and 1,456 genes; 424 of those genes are also directly associated with a disease. The integration of these two data sets predicts diseases that parallel those already known to be associated with arsenic exposure, underscoring the potential value and validity of these inferred relationships.

Mentions: Among the genes with curated arsenic interactions in CTD, 424 have curated relationships with 516 diseases. Therefore, arsenic has inferred relationships with 516 diseases in CTD. Using the hierarchical disease vocabulary in CTD, these diseases were clustered into 26 general categories (see Methods). The most common disease categories associated with arsenic included neoplasms, nervous system diseases, skin diseases, digestive system diseases, metabolic disorders, and immune system diseases (Table 5). Notably, many of these diseases were corroborated in the literature as being associated with arsenic, including malignancies (skin, lung, liver, kidney and bladder cancer), neurological defects (peripheral neuropathy and cognitive impairment), skin lesions, diabetes, and many others (Figure 3) [19-21]. This corroboration supported the value of using CTD-inferred disease relationships to develop novel hypotheses about the health effects of exposure to environmental chemicals.


The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study.

Davis AP, Murphy CG, Rosenstein MC, Wiegers TC, Mattingly CJ - BMC Med Genomics (2008)

Arsenic-gene-disease predictions. CTD describes a molecular interaction between arsenic (As) and 1,456 genes; 424 of those genes are also directly associated with a disease. The integration of these two data sets predicts diseases that parallel those already known to be associated with arsenic exposure, underscoring the potential value and validity of these inferred relationships.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2576347&req=5

Figure 3: Arsenic-gene-disease predictions. CTD describes a molecular interaction between arsenic (As) and 1,456 genes; 424 of those genes are also directly associated with a disease. The integration of these two data sets predicts diseases that parallel those already known to be associated with arsenic exposure, underscoring the potential value and validity of these inferred relationships.
Mentions: Among the genes with curated arsenic interactions in CTD, 424 have curated relationships with 516 diseases. Therefore, arsenic has inferred relationships with 516 diseases in CTD. Using the hierarchical disease vocabulary in CTD, these diseases were clustered into 26 general categories (see Methods). The most common disease categories associated with arsenic included neoplasms, nervous system diseases, skin diseases, digestive system diseases, metabolic disorders, and immune system diseases (Table 5). Notably, many of these diseases were corroborated in the literature as being associated with arsenic, including malignancies (skin, lung, liver, kidney and bladder cancer), neurological defects (peripheral neuropathy and cognitive impairment), skin lesions, diabetes, and many others (Figure 3) [19-21]. This corroboration supported the value of using CTD-inferred disease relationships to develop novel hypotheses about the health effects of exposure to environmental chemicals.

Bottom Line: Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases.The analysis reported here is extensible to any environmental chemical or therapeutic drug.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioinformatics, The Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672 USA. apd@mdibl.org

ABSTRACT

Background: The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate physiological processes. Understanding interactions between environmental chemicals and genes/proteins may provide insights into the mechanisms of chemical actions, disease susceptibility, toxicity, and therapeutic drug interactions. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) provides these insights by curating and integrating data describing relationships between chemicals, genes/proteins, and human diseases. To illustrate the scope and application of CTD, we present an analysis of curated data for the chemical arsenic. Arsenic represents a major global environmental health threat and is associated with many diseases. The mechanisms by which arsenic modulates these diseases are not well understood.

Methods: Curated interactions between arsenic compounds and genes were downloaded using export and batch query tools at CTD. The list of genes was analyzed for molecular interactions, Gene Ontology (GO) terms, KEGG pathway annotations, and inferred disease relationships.

Results: CTD contains curated data from the published literature describing 2,738 molecular interactions between 21 different arsenic compounds and 1,456 genes and proteins. Analysis of these genes and proteins provide insight into the biological functions and molecular networks that are affected by exposure to arsenic, including stress response, apoptosis, cell cycle, and specific protein signaling pathways. Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.

Conclusion: CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases. While many reports describe the molecular response to arsenic, CTD integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug.

No MeSH data available.


Related in: MedlinePlus