Applications of single-cell and bulk RNA sequencing in onco-immunology.

The rising interest for precise characterization of the tumour immune contexture has recently brought forward the high potential of RNA sequencing (RNA-seq) in identifying molecular mechanisms engaged in the response to immunotherapy. In this review, we provide an overview of the major principles of single-cell and conventional (bulk) RNA-seq applied to onco-immunology. We describe standard preprocessing and statistical analyses of data obtained from such techniques and highlight some computational challenges relative to the sequencing of individual cells. We notably provide examples of gene expression analyses such as differential expression analysis, dimensionality reduction, clustering and enrichment analysis. Additionally, we used public data sets to exemplify how deconvolution algorithms can identify and quantify multiple immune subpopulations from either bulk or single-cell RNA-seq. We give examples of machine and deep learning models used to predict patient outcomes and treatment effect from high-dimensional data. Finally, we balance the strengths and weaknesses of single-cell and bulk RNA-seq regarding their applications in the clinic.

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Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement M.K., D.M., M.A., F.X.D. and A.Z. have no conflict of interest to declare. L.V. reports personal fees from Adaptherapy, non-personal fees from Pierre-Fabre and Servier, grants from Bristol-Myers Squibb, all outside the submitted work. As part of the Drug Development Department (DITEP), A.M. and L.V. report being: Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Therapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Xencor. Research Grants from AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Onxeo, Pfizer, Roche, Sanofi. Non-financial support (drug supplied) from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Medimmune, Merck, NH TherAGuiX, Onxeo, Pfizer, Roche. A.Z. was supported by the Ministry of Science and Higher Education of the Russian Federation (Project No. 075-15-2020-808) and by European Union's Horizon 2020 program (grant No. 826121, iPC project).