Machine learning reveals genetic modifiers of the immune microenvironment of cancer.
Cancer systems biology
Microenvironment
Quantitative genetics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
15 Sep 2023
15 Sep 2023
Historique:
received:
06
01
2023
revised:
01
05
2023
accepted:
04
08
2023
medline:
4
9
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
Heritability in the immune tumor microenvironment (iTME) has been widely observed yet remains largely uncharacterized. Here, we developed a machine learning approach to map iTME modifiers within loci from genome-wide association studies (GWASs) for breast cancer (BrCa) incidence. A random forest model was trained on a positive set of immune-oncology (I-O) targets, and then used to assign I-O target probability scores to 1,362 candidate genes in linkage disequilibrium with 155 BrCa GWAS loci. Cluster analysis of the most probable candidates revealed two subfamilies of genes related to effector functions and adaptive immune responses, suggesting that iTME modifiers impact multiple aspects of anticancer immunity. Two of the top ranking BrCa candidates,
Identifiants
pubmed: 37664640
doi: 10.1016/j.isci.2023.107576
pii: S2589-0042(23)01653-X
pmc: PMC10470213
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107576Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
B.R.G., E.K., S.W., J.R., Z.D., and M.J.F. are employees of AbbVie. All animal studies and histological analysis of human breast cancer specimens were conducted at the Medical College of Wisconsin (MCW), at which time M.J.F. was a full-time faculty member of MCW. S.W.T., A.R.P., K.W., A.L., and H.R. are employees of MCW and have no financial relationship with AbbVie to disclose. The design, study conduct, and financial support for all other research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.
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