Accurate estimation of cell composition in bulk expression through robust integration of single-cell information

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Jew , B , Alvarez , M , Rahmani , E , Miao , Z , Ko , A , Garske , K M , Sul , J H , Pietiläinen , K H , Pajukanta , P & Halperin , E 2020 , ' Accurate estimation of cell composition in bulk expression through robust integration of single-cell information ' , Nature Communications , vol. 11 , no. 1 , 1971 . https://doi.org/10.1038/s41467-020-15816-6

Title: Accurate estimation of cell composition in bulk expression through robust integration of single-cell information
Author: Jew, Brandon; Alvarez, Marcus; Rahmani, Elior; Miao, Zong; Ko, Arthur; Garske, Kristina M.; Sul, Jae Hoon; Pietiläinen, Kirsi H.; Pajukanta, Päivi; Halperin, Eran
Contributor organization: HUS Abdominal Center
Department of Medicine
Research Programs Unit
CAMM - Research Program for Clinical and Molecular Metabolism
University of Helsinki
Endokrinologian yksikkö
Helsinki University Hospital Area
Date: 2020-04-24
Language: eng
Number of pages: 11
Belongs to series: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-020-15816-6
URI: http://hdl.handle.net/10138/318653
Abstract: We present Bisque, a tool for estimating cell type proportions in bulk expression. Bisque implements a regression-based approach that utilizes single-cell RNA-seq (scRNA-seq) or single-nucleus RNA-seq (snRNA-seq) data to generate a reference expression profile and learn gene-specific bulk expression transformations to robustly decompose RNA-seq data. These transformations significantly improve decomposition performance compared to existing methods when there is significant technical variation in the generation of the reference profile and observed bulk expression. Importantly, compared to existing methods, our approach is extremely efficient, making it suitable for the analysis of large genomic datasets that are becoming ubiquitous. When applied to subcutaneous adipose and dorsolateral prefrontal cortex expression datasets with both bulk RNA-seq and snRNA-seq data, Bisque replicates previously reported associations between cell type proportions and measured phenotypes across abundant and rare cell types. We further propose an additional mode of operation that merely requires a set of known marker genes.
Subject: ADIPOSE-TISSUE
MICROGLIA
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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