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

Chiao Yu Hsieh, Ching Chih Tu, Jui Hung Hung*

*此作品的通信作者

研究成果: Article同行評審

摘要

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.

原文English
文章編號e202101299
期刊Life Science Alliance
5
發行號10
DOIs
出版狀態Published - 10月 2022

指紋

深入研究「Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap」主題。共同形成了獨特的指紋。

引用此