Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex

Abstract Cellular deconvolution of bulk RNA-sequencing data using single cell/nuclei RNA-seq reference data is an important strategy for estimating cell type composition in heterogeneous tissues, such as the human brain. Here, we generate a multi-assay dataset in postmortem human dorsolateral prefro...

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Main Authors: Louise A. Huuki-Myers, Kelsey D. Montgomery, Sang Ho Kwon, Sophia Cinquemani, Nicholas J. Eagles, Daianna Gonzalez-Padilla, Sean K. Maden, Joel E. Kleinman, Thomas M. Hyde, Stephanie C. Hicks, Kristen R. Maynard, Leonardo Collado-Torres
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Language:English
Published: BMC 2025-04-01
Series:Genome Biology
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Online Access:https://doi.org/10.1186/s13059-025-03552-3
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author Louise A. Huuki-Myers
Kelsey D. Montgomery
Sang Ho Kwon
Sophia Cinquemani
Nicholas J. Eagles
Daianna Gonzalez-Padilla
Sean K. Maden
Joel E. Kleinman
Thomas M. Hyde
Stephanie C. Hicks
Kristen R. Maynard
Leonardo Collado-Torres
author_facet Louise A. Huuki-Myers
Kelsey D. Montgomery
Sang Ho Kwon
Sophia Cinquemani
Nicholas J. Eagles
Daianna Gonzalez-Padilla
Sean K. Maden
Joel E. Kleinman
Thomas M. Hyde
Stephanie C. Hicks
Kristen R. Maynard
Leonardo Collado-Torres
author_sort Louise A. Huuki-Myers
collection DOAJ
description Abstract Cellular deconvolution of bulk RNA-sequencing data using single cell/nuclei RNA-seq reference data is an important strategy for estimating cell type composition in heterogeneous tissues, such as the human brain. Here, we generate a multi-assay dataset in postmortem human dorsolateral prefrontal cortex from 22 tissue blocks, including bulk RNA-seq, reference snRNA-seq, and orthogonal measurement of cell type proportions with RNAScope/ImmunoFluorescence. We use this dataset to evaluate six deconvolution algorithms. Bisque and hspe were the most accurate methods. The dataset, as well as the Mean Ratio gene marker finding method, is made available in the DeconvoBuddies R/Bioconductor package.
format Article
id doaj-art-1619e61dabde4e159e2ba7aea247a097
institution OA Journals
issn 1474-760X
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series Genome Biology
spelling doaj-art-1619e61dabde4e159e2ba7aea247a0972025-08-20T02:12:02ZengBMCGenome Biology1474-760X2025-04-0126113510.1186/s13059-025-03552-3Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortexLouise A. Huuki-Myers0Kelsey D. Montgomery1Sang Ho Kwon2Sophia Cinquemani3Nicholas J. Eagles4Daianna Gonzalez-Padilla5Sean K. Maden6Joel E. Kleinman7Thomas M. Hyde8Stephanie C. Hicks9Kristen R. Maynard10Leonardo Collado-Torres11Lieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthLieber Institute for Brain Development, Johns Hopkins Medical CampusLieber Institute for Brain Development, Johns Hopkins Medical CampusAbstract Cellular deconvolution of bulk RNA-sequencing data using single cell/nuclei RNA-seq reference data is an important strategy for estimating cell type composition in heterogeneous tissues, such as the human brain. Here, we generate a multi-assay dataset in postmortem human dorsolateral prefrontal cortex from 22 tissue blocks, including bulk RNA-seq, reference snRNA-seq, and orthogonal measurement of cell type proportions with RNAScope/ImmunoFluorescence. We use this dataset to evaluate six deconvolution algorithms. Bisque and hspe were the most accurate methods. The dataset, as well as the Mean Ratio gene marker finding method, is made available in the DeconvoBuddies R/Bioconductor package.https://doi.org/10.1186/s13059-025-03552-3DeconvolutionTranscriptomicsRNA-seqsnRNA-seqsmFISHRNAScope
spellingShingle Louise A. Huuki-Myers
Kelsey D. Montgomery
Sang Ho Kwon
Sophia Cinquemani
Nicholas J. Eagles
Daianna Gonzalez-Padilla
Sean K. Maden
Joel E. Kleinman
Thomas M. Hyde
Stephanie C. Hicks
Kristen R. Maynard
Leonardo Collado-Torres
Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
Genome Biology
Deconvolution
Transcriptomics
RNA-seq
snRNA-seq
smFISH
RNAScope
title Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
title_full Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
title_fullStr Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
title_full_unstemmed Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
title_short Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex
title_sort benchmark of cellular deconvolution methods using a multi assay dataset from postmortem human prefrontal cortex
topic Deconvolution
Transcriptomics
RNA-seq
snRNA-seq
smFISH
RNAScope
url https://doi.org/10.1186/s13059-025-03552-3
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