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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
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scDR: Predicting Drug Response at Single-Cell Resolution.

Wanyue Lei1, Mengqin Yuan1, Min Long1

  • 1Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

Genes
|February 25, 2023
PubMed
Summary
This summary is machine-generated.

We developed a single-cell drug response (scDR) prediction method using single-cell RNA sequencing data. This method accurately predicts patient outcomes and drug resistance mechanisms at the single-cell level.

Keywords:
cancerdrug resistancedrug responseheterogeneityscRNA-seq

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Area of Science:

  • Genomics
  • Computational Biology
  • Pharmacology

Background:

  • Tumor heterogeneity impacts drug efficacy.
  • Understanding drug response at single-cell resolution is crucial for personalized medicine.

Purpose of the Study:

  • To develop a precise single-cell drug response (scDR) prediction method for single-cell RNA sequencing (scRNA-seq) data.
  • To validate scDR using diverse transcriptomics datasets and assess its predictive capabilities for cancer prognoses.
  • To explore drug resistance mechanisms using scDR.

Main Methods:

  • Calculated a drug-response score (DRS) per cell by integrating drug-response genes (DRGs) and scRNA-seq gene expression.
  • Validated scDR with internal/external bulk and scRNA-seq data from cell lines and patient tissues.
  • Applied scDR to time-series data to investigate drug resistance mechanisms.

Main Results:

  • scDR accurately predicted drug responses and prognoses for BLCA, PAAD, and STAD.
  • scDR demonstrated higher accuracy compared to existing methods across 53,502 cells from 198 cancer cell lines.
  • Identified an intrinsic resistant cell subgroup in melanoma and explored mechanisms like cell cycle activation.

Conclusions:

  • scDR is a credible method for predicting drug response at single-cell resolution.
  • scDR aids in exploring drug resistance mechanisms.
  • scDR has potential applications in personalized cancer therapy.