PC3T
Han L, Song B, Zhang P, Zhong Z, Zhang Y, Bo X, Wang H, Zhang Y, Cui X, Zhou W
2023 · Communications biology
Cellular transitions hold great promise in translational medicine research.
Abstract
From the original paper, Communications biology · PubMed
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.
Summary
Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how PC3T relates to the cross-modality inverse-design framework of the review.
Why this level
Level 2 because the method instantiates the inverse-design objective through an empirical or learned proxy response map rather than a mechanistic intervention-dependent model. Representation family is signature / state-matching. Cited in §3.3 of the review. Editorial rationale pending review by the maintainer.