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Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures Suphavilai, Chayaporn; Chia, Shumei; Sharma, Ankur; Tu, Lorna; Da Silva, Rafael P.; Mongia, Aanchal; DasGupta, Ramanuj; Nagarajan, Niranjan
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 .
Item Metadata
Title |
Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures
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Creator | |
Publisher |
BioMed Central
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Date Issued |
2021-12-16
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Description |
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
.
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Subject | |
Genre | |
Type | |
Language |
eng
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Date Available |
2022-01-12
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution 4.0 International (CC BY 4.0)
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DOI |
10.14288/1.0406259
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URI | |
Affiliation | |
Citation |
Genome Medicine. 2021 Dec 16;13(1):189
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Publisher DOI |
10.1186/s13073-021-01000-y
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty; Other
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Copyright Holder |
The Author(s)
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Rights URI | |
Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
Attribution 4.0 International (CC BY 4.0)