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Nucleic Acids Res., Nov 20 2023, gkad1087 | https://doi.org/10.1093/nar/gkad1087 DRMref: comprehensive reference map of drug resistance mechanisms in human cancer

Xiaona Liu ¹, Jiahao Yi ², Tina Li ¹, Jianguo Wen ¹, Kexin Huang ³, Jiajia Liu¹, Grant Wang⁴, Pora Kim ¹, Qianqian Song⁵, Xiaobo Zhou ¹

¹Center for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

²Bioinformatics and Biomedical Big Data Mining Laboratory, Department of Medical Informatics, School of Big Health, Guizhou Medical University, Guiyang 550025, China.

³West China Biomedical Big Data Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

⁴Department of Bioengineering, Rice University, Houston, TX 77005, USA.

⁵Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Correspondence: Pora Kim, Qianqian Song, Xiaobo Zhou

Abstract

Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have 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, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in DRMref are browsable and searchable, with detailed annotations provided. Meanwhile, DRMref includes analyses of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, cell-cell interaction and differentially expressed genes in resistant cells. Notably, DRMref investigates the drug resistance mechanisms (e.g. Aberration of Drug's Therapeutic Target, Drug Inactivation by Structure Modification, etc.) in resistant cells. Additional enrichment analysis of hallmark/KEGG (Kyoto Encyclopedia of Genes and Genomes)/GO (Gene Ontology) pathways, as well as the identification of microRNA, motif and transcription factors involved in resistant cells, is provided in DRMref for user's exploration. Overall, DRMref serves as a unique single-cell-based resource for studying drug resistance, drug combination therapy and discovering novel drug targets.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-22)
연구진국외 연구진
분야 의약학 > 유전 및 유전체의학

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