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Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer
Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. DNA methylation, transcripts, protein and glycos...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120220/ https://www.ncbi.nlm.nih.gov/pubmed/29927052 http://dx.doi.org/10.1002/1878-0261.12348 |
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author | Murphy, Keefe Murphy, Brendan T. Boyce, Susie Flynn, Louise Gilgunn, Sarah O'Rourke, Colm J. Rooney, Cathy Stöckmann, Henning Walsh, Anna L. Finn, Stephen O'Kennedy, Richard J. O'Leary, John Pennington, Stephen R. Perry, Antoinette S. Rudd, Pauline M. Saldova, Radka Sheils, Orla Shields, Denis C. Watson, R. William |
author_facet | Murphy, Keefe Murphy, Brendan T. Boyce, Susie Flynn, Louise Gilgunn, Sarah O'Rourke, Colm J. Rooney, Cathy Stöckmann, Henning Walsh, Anna L. Finn, Stephen O'Kennedy, Richard J. O'Leary, John Pennington, Stephen R. Perry, Antoinette S. Rudd, Pauline M. Saldova, Radka Sheils, Orla Shields, Denis C. Watson, R. William |
author_sort | Murphy, Keefe |
collection | PubMed |
description | Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. DNA methylation, transcripts, protein and glycosylation biomarkers were assessed in a single cohort of patients treated by radical prostatectomy. Novel multiblock statistical data integration approaches were used to deal with missing data and modelled via stepwise multinomial logistic regression, or LASSO. After applying leave‐one‐out cross‐validation to each model, the probabilistic predictions of disease type for each individual panel were aggregated to improve prediction accuracy using all available information for a given patient. Through assessment of three performance parameters of area under the curve (AUC) values, calibration and decision curve analysis, the study identified an integrated biomarker panel which predicts disease type with a high level of accuracy, with Multi AUC value of 0.91 (0.89, 0.94) and Ordinal C‐Index (ORC) value of 0.94 (0.91, 0.96), which was significantly improved compared to the values for the clinical panel alone of 0.67 (0.62, 0.72) Multi AUC and 0.72 (0.67, 0.78) ORC. Biomarker integration across different omic platforms significantly improves prediction accuracy. We provide a novel multiplatform approach for the analysis, determination and performance assessment of novel panels which can be applied to other diseases. With further refinement and validation, this panel could form a tool to help inform appropriate treatment strategies impacting on patient outcome in early stage prostate cancer. |
format | Online Article Text |
id | pubmed-6120220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61202202018-09-05 Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer Murphy, Keefe Murphy, Brendan T. Boyce, Susie Flynn, Louise Gilgunn, Sarah O'Rourke, Colm J. Rooney, Cathy Stöckmann, Henning Walsh, Anna L. Finn, Stephen O'Kennedy, Richard J. O'Leary, John Pennington, Stephen R. Perry, Antoinette S. Rudd, Pauline M. Saldova, Radka Sheils, Orla Shields, Denis C. Watson, R. William Mol Oncol Research Articles Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone. DNA methylation, transcripts, protein and glycosylation biomarkers were assessed in a single cohort of patients treated by radical prostatectomy. Novel multiblock statistical data integration approaches were used to deal with missing data and modelled via stepwise multinomial logistic regression, or LASSO. After applying leave‐one‐out cross‐validation to each model, the probabilistic predictions of disease type for each individual panel were aggregated to improve prediction accuracy using all available information for a given patient. Through assessment of three performance parameters of area under the curve (AUC) values, calibration and decision curve analysis, the study identified an integrated biomarker panel which predicts disease type with a high level of accuracy, with Multi AUC value of 0.91 (0.89, 0.94) and Ordinal C‐Index (ORC) value of 0.94 (0.91, 0.96), which was significantly improved compared to the values for the clinical panel alone of 0.67 (0.62, 0.72) Multi AUC and 0.72 (0.67, 0.78) ORC. Biomarker integration across different omic platforms significantly improves prediction accuracy. We provide a novel multiplatform approach for the analysis, determination and performance assessment of novel panels which can be applied to other diseases. With further refinement and validation, this panel could form a tool to help inform appropriate treatment strategies impacting on patient outcome in early stage prostate cancer. John Wiley and Sons Inc. 2018-08-07 2018-09 /pmc/articles/PMC6120220/ /pubmed/29927052 http://dx.doi.org/10.1002/1878-0261.12348 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Murphy, Keefe Murphy, Brendan T. Boyce, Susie Flynn, Louise Gilgunn, Sarah O'Rourke, Colm J. Rooney, Cathy Stöckmann, Henning Walsh, Anna L. Finn, Stephen O'Kennedy, Richard J. O'Leary, John Pennington, Stephen R. Perry, Antoinette S. Rudd, Pauline M. Saldova, Radka Sheils, Orla Shields, Denis C. Watson, R. William Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title | Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title_full | Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title_fullStr | Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title_full_unstemmed | Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title_short | Integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
title_sort | integrating biomarkers across omic platforms: an approach to improve stratification of patients with indolent and aggressive prostate cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120220/ https://www.ncbi.nlm.nih.gov/pubmed/29927052 http://dx.doi.org/10.1002/1878-0261.12348 |
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