Accurate estimation of cell composition in bulk expression through robust integration of single-cell information.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
03
06
2019
accepted:
25
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
4
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32332754
doi: 10.1038/s41467-020-15816-6
pii: 10.1038/s41467-020-15816-6
pmc: PMC7181686
doi:
Substances chimiques
RNA, Small Cytoplasmic
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1971Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG010505
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL028481
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105561
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL095056
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL142180
Pays : United States
Commentaires et corrections
Type : ErratumIn
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