Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures

Autor: Chayaporn Suphavilai, Shumei Chia, Ankur Sharma, Lorna Tu, Rafael Peres Da Silva, Aanchal Mongia, Ramanuj DasGupta, Niranjan Nagarajan
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Genome Medicine, Vol 13, Iss 1, Pp 1-14 (2021)
Druh dokumentu: article
ISSN: 1756-994X
DOI: 10.1186/s13073-021-01000-y
Popis: Abstract While understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validity of CaDRReS-Sc’s monotherapy (Pearson r>0.6) and combinatorial predictions targeting clone-specific vulnerabilities (>10% improvement). Applying CaDRReS-Sc to rapidly expanding scRNA-seq compendiums can serve as in silico screen to accelerate drug-repurposing studies. Availability: https://github.com/CSB5/CaDRReS-Sc .
Databáze: Directory of Open Access Journals