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Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis
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NetExtractor: Extracting a Cerebellar Tissue Gene Regulatory Network Using Differentially Expressed High Mutual

Benafsh Husain1, Allison R Hickman2, Yuqing Hang2

  • 1Biomedical Data Science and Informatics Program, Clemson University, Clemson, SC.

G3 (Bethesda, Md.)
|July 16, 2020
PubMed
Summary

Our NetExtractor algorithm identifies complex, non-linear gene expression relationships missed by traditional methods. It constructs novel gene co-expression networks (GCNs) for brain tissue, revealing biologically relevant connections.

Keywords:
Cerebellar geneDifferential RNAMutual Informationexpressionregulatory network

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Area of Science:

  • Genomics
  • Computational Biology
  • Systems Biology

Background:

  • Traditional gene co-expression network (GCN) construction relies on linear correlations (Pearson, Spearman), failing to capture non-linear dependencies.
  • Noise and sub-population structures in gene expression data obscure biologically relevant gene relationships.
  • Existing methods struggle to identify complex, latent bigenic expression patterns.

Purpose of the Study:

  • To develop and validate a novel algorithm, NetExtractor, for detecting non-linear, differential bigenic expression relationships.
  • To overcome limitations of conventional correlation-based methods in GCN construction.
  • To identify novel gene expression networks in brain tissue.

Main Methods:

  • NetExtractor employs Gaussian mixture models (GMMs) to identify sample sub-populations.
  • Mutual information (MI) analysis is used to detect non-linear bigenic expression relationships.
  • Application to Genotype-Tissue Expression (GTEx) brain RNA profiles and integration with PsychENCODE gene regulatory network (GRN) data.

Main Results:

  • NetExtractor successfully identified non-linear gene expression relationships in brain tissue.
  • A brain tissue-specific gene expression relationship network was constructed, enriched for cerebellar and cerebellar hemisphere edges.
  • A cerebellar cortex (cerebellar) gene regulatory network (GRN) was generated, linked to transcriptionally active regions.

Conclusions:

  • NetExtractor effectively detects biologically relevant and novel non-linear binary gene relationships.
  • The algorithm enhances the construction of gene co-expression networks by accounting for data complexity.
  • This approach provides a powerful tool for uncovering intricate gene interactions in complex tissues like the brain.