Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.

Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can b...

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Autores principales: Maike Ahrens, Michael Turewicz, Swaantje Casjens, Caroline May, Beate Pesch, Christian Stephan, Dirk Woitalla, Ralf Gold, Thomas Brüning, Helmut E Meyer, Jörg Rahnenführer, Martin Eisenacher
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:cbf81d05f4f24ccf8e5cf561a07e8ead2021-11-18T08:45:05ZDetection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.1932-620310.1371/journal.pone.0079380https://doaj.org/article/cbf81d05f4f24ccf8e5cf561a07e8ead2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278130/?tool=EBIhttps://doaj.org/toc/1932-6203Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can be characterized by differential expression for only a subgroup-specific set of genes or proteins. Finding such genes and corresponding patient subgroups can help in understanding pathological pathways, diagnosis and defining drug targets. The size of the subgroup and the type of differential expression determine the optimal strategy for subgroup identification. To date, commonly used software packages hardly provide statistical tests and methods for the detection of such subgroups. Different univariate methods for subgroup detection are characterized and compared, both on simulated and on real data. We present an advanced design for simulation studies: Data is simulated under different distributional assumptions for the expression of the subgroup, and performance results are compared against theoretical upper bounds. For each distribution, different degrees of deviation from the majority of observations are considered for the subgroup. We evaluate classical approaches as well as various new suggestions in the context of omics data, including outlier sum, PADGE, and kurtosis. We also propose the new FisherSum score. ROC curve analysis and AUC values are used to quantify the ability of the methods to distinguish between genes or proteins with and without certain subgroup patterns. In general, FisherSum for small subgroups and t-test for large subgroups achieve best results. We apply each method to a case-control study on Parkinson's disease and underline the biological benefit of the new method.Maike AhrensMichael TurewiczSwaantje CasjensCaroline MayBeate PeschChristian StephanDirk WoitallaRalf GoldThomas BrüningHelmut E MeyerJörg RahnenführerMartin EisenacherPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79380 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maike Ahrens
Michael Turewicz
Swaantje Casjens
Caroline May
Beate Pesch
Christian Stephan
Dirk Woitalla
Ralf Gold
Thomas Brüning
Helmut E Meyer
Jörg Rahnenführer
Martin Eisenacher
Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
description Detection of yet unknown subgroups showing differential gene or protein expression is a frequent goal in the analysis of modern molecular data. Applications range from cancer biology over developmental biology to toxicology. Often a control and an experimental group are compared, and subgroups can be characterized by differential expression for only a subgroup-specific set of genes or proteins. Finding such genes and corresponding patient subgroups can help in understanding pathological pathways, diagnosis and defining drug targets. The size of the subgroup and the type of differential expression determine the optimal strategy for subgroup identification. To date, commonly used software packages hardly provide statistical tests and methods for the detection of such subgroups. Different univariate methods for subgroup detection are characterized and compared, both on simulated and on real data. We present an advanced design for simulation studies: Data is simulated under different distributional assumptions for the expression of the subgroup, and performance results are compared against theoretical upper bounds. For each distribution, different degrees of deviation from the majority of observations are considered for the subgroup. We evaluate classical approaches as well as various new suggestions in the context of omics data, including outlier sum, PADGE, and kurtosis. We also propose the new FisherSum score. ROC curve analysis and AUC values are used to quantify the ability of the methods to distinguish between genes or proteins with and without certain subgroup patterns. In general, FisherSum for small subgroups and t-test for large subgroups achieve best results. We apply each method to a case-control study on Parkinson's disease and underline the biological benefit of the new method.
format article
author Maike Ahrens
Michael Turewicz
Swaantje Casjens
Caroline May
Beate Pesch
Christian Stephan
Dirk Woitalla
Ralf Gold
Thomas Brüning
Helmut E Meyer
Jörg Rahnenführer
Martin Eisenacher
author_facet Maike Ahrens
Michael Turewicz
Swaantje Casjens
Caroline May
Beate Pesch
Christian Stephan
Dirk Woitalla
Ralf Gold
Thomas Brüning
Helmut E Meyer
Jörg Rahnenführer
Martin Eisenacher
author_sort Maike Ahrens
title Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
title_short Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
title_full Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
title_fullStr Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
title_full_unstemmed Detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
title_sort detection of patient subgroups with differential expression in omics data: a comprehensive comparison of univariate measures.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/cbf81d05f4f24ccf8e5cf561a07e8ead
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