Medical College of Wisconsin
CTSIResearch InformaticsREDCap

Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets. Nat Commun 2023 May 27;14(1):3064

Date

05/28/2023

Pubmed ID

37244909

Pubmed Central ID

PMC10224950

DOI

10.1038/s41467-023-38637-9

Scopus ID

2-s2.0-85160374592 (requires institutional sign-in at Scopus site)   72 Citations

Abstract

Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. Single-cell technologies such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific GRNs are limited in their ability to integrate scRNA-seq and scATAC-seq measurements and to model network dynamics on a cell lineage. To address this challenge, we have developed single-cell Multi-Task Network Inference (scMTNI), a multi-task learning framework to infer the GRN for each cell type on a lineage from scRNA-seq and scATAC-seq data. Using simulated and real datasets, we show that scMTNI is a broadly applicable framework for linear and branching lineages that accurately infers GRN dynamics and identifies key regulators of fate transitions for diverse processes such as cellular reprogramming and differentiation.

Author List

Zhang S, Pyne S, Pietrzak S, Halberg S, McCalla SG, Siahpirani AF, Sridharan R, Roy S

Author

Stefan Joseph Pietrzak PhD, BS Postdoctoral Researcher in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Lineage
Chromatin
Gene Regulatory Networks
Single-Cell Analysis
Transcription Factors