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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Inference of Gene Regulatory Network from Single-Cell Transcriptomic Data Using pySCENIC.

Nilesh Kumar1, Bharat Mishra1, Mohammad Athar2

  • 1Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA.

Methods in Molecular Biology (Clifton, N.J.)
|July 12, 2021
PubMed
Summary

We introduce pySCENIC, a fast Python tool for analyzing single-cell RNA sequencing data. It infers gene regulatory networks (GRNs) and cell-specific transcription factor activity from gene expression patterns.

Keywords:
Gene co-expression networkGene regulatory networkRNA-Seq count datascRNA-seq

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Area of Science:

  • Genomics
  • Transcriptomics
  • Epigenomics
  • Computational Biology

Background:

  • Next-generation sequencing (NGS) enables single-cell profiling.
  • Single-cell RNA sequencing (scRNA-seq) is crucial for characterizing cell populations and regulatory mechanisms.
  • Gene regulatory networks (GRNs) involve genes and transcription factors (TFs).

Purpose of the Study:

  • To present pySCENIC, a rapid Python implementation of the SCENIC pipeline.
  • To enable inference of cell-specific GRNs from scRNA-seq data.
  • To map TFs to gene regulatory networks and integrate diverse cell types.

Main Methods:

  • Utilizes scRNA-seq data for GRN inference.
  • Incorporates GRNBoost2 and GENIE3 algorithms for efficient GRN construction.
  • Employs a three-step pipeline: co-expression target identification, TF-motif enrichment for regulon discovery, and regulon activity scoring.

Main Results:

  • Provides a lightning-fast Python implementation of the SCENIC pipeline.
  • Facilitates the mapping of TFs onto GRNs.
  • Enables the inference of cell-specific GRNs by integrating various cell types.

Conclusions:

  • pySCENIC offers an efficient computational tool for GRN inference from scRNA-seq data.
  • The pipeline effectively identifies direct TF targets and assesses regulon activity across single cells.
  • Accelerates the analysis of gene regulatory mechanisms at the single-cell level.