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PC3T: a signature-driven predictor of chemical compounds for cellular transition

ABSTRACT: PC3T: a signature-driven predictor of chemical compounds for cellular transition

PROVIDER: PRJNA970319 | ENA |

REPOSITORIES: ENA

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PC3T: a signature-driven predictor of chemical compounds for cellular transition.

Project description:Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tunable approach to overcome these issues. Here, we present PC3T, a computational framework to enrich molecules that induce desired cellular transitions, and PC3T was able to consistently enrich small molecules that had been experimentally validated in both bulk and single-cell datasets. We then predicted small molecule reprogramming of fibroblasts into hepatic progenitor-like cells (HPLCs). The converted cells exhibited epithelial cell-like morphology and HPLC-like gene expression pattern. Hepatic functions were also observed, such as glycogen storage and lipid accumulation. Finally, we collected and manually curated a cell state transition resource containing 224 time-course gene expression datasets and 153 cell types. Our framework, together with the data resource, is freely available at http://pc3t.idrug.net.cn/ . We believe that PC3T is a powerful tool to promote chemical-induced cell state transitions.

| S-EPMC10533498 | biostudies-literature

PC3T: a signature-driven predictor of chemical compounds for cellular transition

2023-05-09 | GSE231967 | GEO

Gene expression analysis of dendritic cells treated with small chemical compounds

Project description:Identification of newer compounds to modulate dendritic cell functions. Total RNA obtained from bone marrow-derived dendritic cells treated for 6 hours with small chemical compounds or vehicle alone in the presence or absence of lipopolysaccharide (LPS).

2011-09-18 | E-GEOD-15360 | biostudies-arrayexpress

A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion [Bulk RNA-seq]

Project description:Cellular conversion can be induced by perturbing a handful of key transcription factors (TFs). Replacement of direct manipulation of key TFs with chemical compounds offers a less laborious and safer strategy to drive cellular conversion for regenerative medicine. Nevertheless, identifying optimal chemical compounds currently requires large-scale screening of chemical libraries, which is resource-intensive. Existing computational methods aim at predicting cell conversion TFs, however there are no methods for identifying chemical compounds targeting these TFs. Here, we develop a single cell-based platform (SiPer) to systematically prioritize chemical compounds targeting desired TFs to guide cellular conversions. SiPer integrates a large compendium of chemical perturbations on non-cancer cells with a network model, and predicted known and novel chemical compounds in diverse cell conversion examples. Importantly, we applied SiPer to develop a highly efficient protocol for human hepatic maturation. Overall, SiPer provides a valuable resource to efficiently identify chemical compounds for cell conversion.

2022-11-17 | GSE162908 | GEO

A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion [Single-cell RNA-seq]

Project description:Conversion of cellular identity can be achieved safely, without genetic manipulation, by inducing signalling perturbations with chemical compounds to target cell fate-governing transcription factors (TFs). However, chemical-induced cellular conversion currently requires large-scale screening of small compounds, which is time- and labour-intensive. There are no existing computational approaches that facilitate chemical conversion of cell fate. Here, we develop a computational framework (SiPer) to systematically predict chemical compounds specifically targeting desired sets of TFs to direct cellular conversion. This framework integrates a large compendium of chemical perturbation datasets with a network model. We show that SiPer is generally applicable to diverse cellular conversion examples, recapitulating the known chemical compounds and their corresponding protein targets. Furthermore, using chemical compounds predicted by SiPer, we develop a highly efficient protocol for the generation of functional human induced hepatocytes (hiHeps). These results demonstrate that SiPer provides a valuable resource to efficiently identify chemical compounds for cellular conversion.

2022-11-17 | GSE162909 | GEO

A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats

Project description:A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats

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Human toxicology-relevant cell lines treated with three doses of 34 chemical compounds

Project description:Human toxicology-relevant cell lines treated with three doses of 34 chemical compounds

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A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats [drug treatment]

Project description:A chemical screen identifies compounds limiting the toxicity of C9ORF72 dipeptide repeats [drug treatment]

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Chemical-Induced Phase Transition and Global Conformational Reorganization of Chromatin [RNA-seq]

Project description:Chemical-Induced Phase Transition and Global Conformational Reorganization of Chromatin [RNA-seq]

| PRJNA918623 | ENA

Chemical-Induced Phase Transition and Global Conformational Reorganization of Chromatin [ATAC-seq]

Project description:Chemical-Induced Phase Transition and Global Conformational Reorganization of Chromatin [ATAC-seq]

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