Performance of tumour microenvironment deconvolution methods in breast cancer using single-cell simulated bulk mixtures.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
16 09 2023
Historique:
received: 31 07 2022
accepted: 01 09 2023
medline: 18 9 2023
pubmed: 17 9 2023
entrez: 16 9 2023
Statut: epublish

Résumé

Cells within the tumour microenvironment (TME) can impact tumour development and influence treatment response. Computational approaches have been developed to deconvolve the TME from bulk RNA-seq. Using scRNA-seq profiling from breast tumours we simulate thousands of bulk mixtures, representing tumour purities and cell lineages, to compare the performance of nine TME deconvolution methods (BayesPrism, Scaden, CIBERSORTx, MuSiC, DWLS, hspe, CPM, Bisque, and EPIC). Some methods are more robust in deconvolving mixtures with high tumour purity levels. Most methods tend to mis-predict normal epithelial for cancer epithelial as tumour purity increases, a finding that is validated in two independent datasets. The breast cancer molecular subtype influences this mis-prediction. BayesPrism and DWLS have the lowest combined numbers of false positives and false negatives, and have the best performance when deconvolving granular immune lineages. Our findings highlight the need for more single-cell characterisation of rarer cell types, and suggest that tumour cell compositions should be considered when deconvolving the TME.

Identifiants

pubmed: 37717006
doi: 10.1038/s41467-023-41385-5
pii: 10.1038/s41467-023-41385-5
pmc: PMC10505141
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5758

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Khoa A Tran (KA)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia.

Venkateswar Addala (V)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Rebecca L Johnston (RL)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

David Lovell (D)

School of Computer Science, Queensland University of Technology, Brisbane, QLD, 4000, Australia.
QUT Centre for Data Science, Brisbane, QLD, 4000, Australia.

Andrew Bradley (A)

Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, 4000, Australia.

Lambros T Koufariotis (LT)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Scott Wood (S)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Sunny Z Wu (SZ)

Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, 2052, Australia.

Daniel Roden (D)

Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, 2052, Australia.

Ghamdan Al-Eryani (G)

Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, 2052, Australia.

Alexander Swarbrick (A)

Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, 2052, Australia.

Elizabeth D Williams (ED)

School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia.
Australian Prostate Cancer Research Centre - Queensland (APCRC-Q) and Queensland Bladder Cancer Initiative (QBCI), Brisbane, QLD, 4000, Australia.

John V Pearson (JV)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Olga Kondrashova (O)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Nicola Waddell (N)

Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia. Nic.waddell@qimrberghofer.edu.au.
School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia. Nic.waddell@qimrberghofer.edu.au.

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