Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and per...

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Main Authors: Heewon Park, Teppei Shimamura, Satoru Miyano, Seiya Imoto
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4201473?pdf=render
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author Heewon Park
Teppei Shimamura
Satoru Miyano
Seiya Imoto
author_facet Heewon Park
Teppei Shimamura
Satoru Miyano
Seiya Imoto
author_sort Heewon Park
collection DOAJ
description The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc.) and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.
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spelling doaj.art-683f2ee6eb2e447f8e020f86ae42e7042022-12-22T03:34:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10899010.1371/journal.pone.0108990Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.Heewon ParkTeppei ShimamuraSatoru MiyanoSeiya ImotoThe personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc.) and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.http://europepmc.org/articles/PMC4201473?pdf=render
spellingShingle Heewon Park
Teppei Shimamura
Satoru Miyano
Seiya Imoto
Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
PLoS ONE
title Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
title_full Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
title_fullStr Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
title_full_unstemmed Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
title_short Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.
title_sort robust prediction of anti cancer drug sensitivity and sensitivity specific biomarker
url http://europepmc.org/articles/PMC4201473?pdf=render
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AT teppeishimamura robustpredictionofanticancerdrugsensitivityandsensitivityspecificbiomarker
AT satorumiyano robustpredictionofanticancerdrugsensitivityandsensitivityspecificbiomarker
AT seiyaimoto robustpredictionofanticancerdrugsensitivityandsensitivityspecificbiomarker