Amirkhah, RahelehGilroy, KathrynMalla, Sudhir B.Lannagan, Tamsin R. M.Byrne, Ryan M,Fisher, Natalie C.Corry, Shania M.Mohamed, Noha-EhssanNaderi-Meshkin, HojjatMills, Megan L.Campbell, Andrew D.Ridgeway, Rachel A.Ahmaderaghi, BaharakMurray, RichardBerenguer Llergo, AntoniSanz Pamplona, RebecaVillanueva Garatachea, AlbertoBatlle, EduardSalazar Soler, RamónLawler, MarkSansom, Owen J.Dunne, Philip D. J.2024-01-302024-01-302023-01-300007-0920https://hdl.handle.net/2445/206667Background: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. Methods: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. Results: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. Conclusions: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.11 p.application/pdfeng(c) Raheleh Amirkhah et al., 2023Càncer colorectalBiologia molecularRatolins (Animals de laboratori)Colorectal cancerMolecular biologyMice (Laboratory animals)info:eu-repo/semantics/article7288432024-01-30info:eu-repo/semantics/openAccess6575480