Dataset Information

Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap.

ABSTRACT: The connectivity among signatures upon perturbations curated in the CMap library provides a valuable resource for understanding therapeutic pathways and biological processes associated with the drugs and diseases. However, because of the nature of bulk-level expression profiling by the L1000 assay, intraclonal heterogeneity and subpopulation compositional change that could contribute to the responses to perturbations are largely neglected, hampering the interpretability and reproducibility of the connections. In this work, we proposed a computational framework, Premnas, to estimate the abundance of undetermined subpopulations from L1000 profiles in CMap directly according to an ad hoc subpopulation representation learned from a well-normalized batch of single-cell RNA-seq datasets by the archetypal analysis. By recovering the information of subpopulation changes upon perturbation, the potentials of drug-resistant/susceptible subpopulations with CMap L1000 were further explored and examined. The proposed framework enables a new perspective to understand the connectivity among cellular signatures and expands the scope of the CMAP and other similar perturbation datasets limited by the bulk profiling technology.

SUBMITTER: Hsieh CY

PROVIDER: S-EPMC9187873 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap.

Hsieh Chiao-Yu CY Tu Ching-Chih CC Hung Jui-Hung JH

Life science alliance 20220610 10

The connectivity among signatures upon perturbations curated in the CMap library provides a valuable resource for understanding therapeutic pathways and biological processes associated with the drugs and diseases. However, because of the nature of bulk-level expression profiling by the L1000 assay, intraclonal heterogeneity and subpopulation compositional change that could contribute to the responses to perturbations are largely neglected, hampering the interpretability and reproducibility of th ...[more]

PMID: 35688486

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Dataset Information

Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap.

Publications

Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap.

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