scDrugAtlas: an integrative single-cell drug response atlas for unraveling tumor heterogeneity in therapeutic efficacy

Abstract

Tumor heterogeneity often leads to substantial differences in responses to same drug treatment. The presence of pre-existing or acquired drug-resistant cell subpopulations within a tumor survive and proliferate, ultimately resulting in tumor relapse and metastasis. The drug resistance is the leading cause of failure in clinical tumor therapy. Therefore, accurate identification of drug-resistant tumor cell subpopulations could greatly facilitate the precision medicine and novel drug development. However, the scarcity of single-cell drug response data significantly hinders the exploration of tumor cell resistance mechanisms and the development of computational predictive methods. In this paper, we propose scDrugAtlas, a comprehensive database devoted to integrating the drug response data at single-cell level. We manually compiled more than 100 datasets containing single-cell drug responses from various public resources. The current version comprises large-scale single-cell transcriptional profiles and drug response labels from more than 1,000 samples (cell line, mouse, PDX models, patients and bacterium), across 66 unique drugs and 13 major cancer types. Particularly, we assigned a confidence level to each response label based on the tissue source (primary or relapse/metastasis), drug exposure time and drug-induced cell phenotype. We believe scDrugAtlas could greatly facilitate the Bioinformatics community for developing computational models and biologists for identifying drug-resistant tumor cells and underlying molecular mechanism. The scDrugAtlas database is available at: http://drug.hliulab.tech/scDrugAtlas/.