PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.

The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the...

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Autores principales:	Wenlian Qiao, Gerald Quon, Elizabeth Csaszar, Mei Yu, Quaid Morris, Peter W Zandstra
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ec7091913adf4e83b105c09ea43da92f
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spelling	oai:doaj.org-article:ec7091913adf4e83b105c09ea43da92f2021-11-18T05:52:37ZPERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.1553-734X1553-735810.1371/journal.pcbi.1002838https://doaj.org/article/ec7091913adf4e83b105c09ea43da92f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284283/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity.Wenlian QiaoGerald QuonElizabeth CsaszarMei YuQuaid MorrisPeter W ZandstraPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 12, p e1002838 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Wenlian Qiao Gerald Quon Elizabeth Csaszar Mei Yu Quaid Morris Peter W Zandstra PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
description	The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity.
format	article
author	Wenlian Qiao Gerald Quon Elizabeth Csaszar Mei Yu Quaid Morris Peter W Zandstra
author_facet	Wenlian Qiao Gerald Quon Elizabeth Csaszar Mei Yu Quaid Morris Peter W Zandstra
author_sort	Wenlian Qiao
title	PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
title_short	PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
title_full	PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
title_fullStr	PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
title_full_unstemmed	PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
title_sort	pert: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/ec7091913adf4e83b105c09ea43da92f
work_keys_str_mv	AT wenlianqiao pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions AT geraldquon pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions AT elizabethcsaszar pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions AT meiyu pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions AT quaidmorris pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions AT peterwzandstra pertamethodforexpressiondeconvolutionofhumanbloodsamplesfromvariedmicroenvironmentalanddevelopmentalconditions
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PERT: a method for expression deconvolution of human blood samples from varied microenvironmental and developmental conditions.

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