DRMref: compr ehensive r efer ence map of drug r esistance mechanisms in human cancer

Abstract

Drug resistance posesã significant challenge in cancer treatment. Despite the initial effectiveness of therapies suchãs chemotherapy, targeted therapyãnd immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistanceãt cell le v el. Herein, w e ha v e built the DRMref database ( https://ccsm.uth.edu/ DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, co v ering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimensãnd 42 drugs. All datasets in DRMrefãre browsableãnd searchable, with detailedãnnotations pro vided. Mean while, DRMref includesãnalyses of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, cell-cell interactionãnd differentially expressed genes in resistãnt cells. Notãbly, DRMref in v estigates the drug resistãnce mechanisms (e.g . Aberration of Drug' s Therapeutic Tãrget, Drug Inactivãtion b y Str uct ure Modification, etc.) in resistant cells. A dditional enrichmentãnaly sis of hallmark / KEGG (Ky oto Ency clopedia of Genesãnd Genomes) / GO (Gene Ontology) pathwã y s,ãs w ellãs the identification of microRNA, motifãnd transcription fãctors in v olv ed in resistant cells, is provided in DRMref for user's exploration. Overall, DRMref servesãsã unique single-cell-based resource for st udying dr ug resistance, drug combination therapyãnd discovering novel drug targets.