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Candidate biomarker assessment for pharmacological response
Using the information from our CellMiner (https://discover.nci.nih.gov/cellminer/) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-based applications, we identified 3978 molecular events with significant links to pharmacological response for genes that are either targets, biomarker...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348063/ https://www.ncbi.nlm.nih.gov/pubmed/32652468 http://dx.doi.org/10.1016/j.tranon.2020.100830 |
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author | Reinhold, William C. Elloumi, Fathi Varma, Sudhir Robert, Jacques Mills, Gordon B. Pommier, Yves |
author_facet | Reinhold, William C. Elloumi, Fathi Varma, Sudhir Robert, Jacques Mills, Gordon B. Pommier, Yves |
author_sort | Reinhold, William C. |
collection | PubMed |
description | Using the information from our CellMiner (https://discover.nci.nih.gov/cellminer/) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-based applications, we identified 3978 molecular events with significant links to pharmacological response for genes that are either targets, biomarkers, or have established causal linkage to drugs. Molecular events included DNA copy number, methylation and mutation; and transcript; and whole or phospho-protein expression for the NCI-60 human cancer cell lines. While all forms of molecular data were informative in some (gene-drug) pairings, the type of significantly linked molecular events was found to vary widely by drug. Some forms of molecular data were found to have more frequent significant correlation than others. Leading were phosphoproteins as measured by antibody (31%), followed by transcript as measured by microarray (16%), and total protein levels as measured by mass spectrometry or antibody (14%). All other measurements ranged between 5 and 11%. Data reliability was underscored by concordant results when using differing drugs with the same targets, as well as different measurements of the same molecular parameter. The significance of correlations of the various molecular parameters to the pharmacological responses provides functional indication of those parameters that are biologically relevant for each gene-drug pairing, as well as comparisons between measurement types. |
format | Online Article Text |
id | pubmed-7348063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-73480632020-07-14 Candidate biomarker assessment for pharmacological response Reinhold, William C. Elloumi, Fathi Varma, Sudhir Robert, Jacques Mills, Gordon B. Pommier, Yves Transl Oncol Original article Using the information from our CellMiner (https://discover.nci.nih.gov/cellminer/) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-based applications, we identified 3978 molecular events with significant links to pharmacological response for genes that are either targets, biomarkers, or have established causal linkage to drugs. Molecular events included DNA copy number, methylation and mutation; and transcript; and whole or phospho-protein expression for the NCI-60 human cancer cell lines. While all forms of molecular data were informative in some (gene-drug) pairings, the type of significantly linked molecular events was found to vary widely by drug. Some forms of molecular data were found to have more frequent significant correlation than others. Leading were phosphoproteins as measured by antibody (31%), followed by transcript as measured by microarray (16%), and total protein levels as measured by mass spectrometry or antibody (14%). All other measurements ranged between 5 and 11%. Data reliability was underscored by concordant results when using differing drugs with the same targets, as well as different measurements of the same molecular parameter. The significance of correlations of the various molecular parameters to the pharmacological responses provides functional indication of those parameters that are biologically relevant for each gene-drug pairing, as well as comparisons between measurement types. Neoplasia Press 2020-07-08 /pmc/articles/PMC7348063/ /pubmed/32652468 http://dx.doi.org/10.1016/j.tranon.2020.100830 Text en © 2020 Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Reinhold, William C. Elloumi, Fathi Varma, Sudhir Robert, Jacques Mills, Gordon B. Pommier, Yves Candidate biomarker assessment for pharmacological response |
title | Candidate biomarker assessment for pharmacological response |
title_full | Candidate biomarker assessment for pharmacological response |
title_fullStr | Candidate biomarker assessment for pharmacological response |
title_full_unstemmed | Candidate biomarker assessment for pharmacological response |
title_short | Candidate biomarker assessment for pharmacological response |
title_sort | candidate biomarker assessment for pharmacological response |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348063/ https://www.ncbi.nlm.nih.gov/pubmed/32652468 http://dx.doi.org/10.1016/j.tranon.2020.100830 |
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