Mapping single-cell developmental potential in health and disease with interpretable deep learning.

Autor: Kang M, Armenteros JJA, Gulati GS, Gleyzer R, Avagyan S, Brown EL, Zhang W, Usmani A, Earland N, Wu Z, Zou J, Fields RC, Chen DY, Chaudhuri AA, Newman AM
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 21. Date of Electronic Publication: 2024 Mar 21.
DOI: 10.1101/2024.03.19.585637
Abstrakt: Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cell fate in developmental systems. However, identifying the molecular hallmarks of potency - the capacity of a cell to differentiate into other cell types - has remained challenging. Here, we introduce CytoTRACE 2, an interpretable deep learning framework for characterizing potency and differentiation states on an absolute scale from scRNA-seq data. Across 31 human and mouse scRNA-seq datasets encompassing 28 tissue types, CytoTRACE 2 outperformed existing methods for recovering experimentally determined potency levels and differentiation states covering the entire range of cellular ontogeny. Moreover, it reconstructed the temporal hierarchy of mouse embryogenesis across 62 timepoints; identified pan-tissue expression programs that discriminate major potency levels; and facilitated discovery of cellular phenotypes in cancer linked to survival and immunotherapy resistance. Our results illuminate a fundamental feature of cell biology and provide a broadly applicable platform for delineating single-cell differentiation landscapes in health and disease.
Databáze: MEDLINE