Gene Cascade Finder: A tool for identification of gene cascades and its application in Caenorhabditis elegans

PLoS One. 2019 Sep 10;14(9):e0215187. doi: 10.1371/journal.pone.0215187. eCollection 2019.


Obtaining a comprehensive understanding of the gene regulatory networks, or gene cascades, involved in cell fate determination and cell lineage segregation in Caenorhabditis elegans is a long-standing challenge. Although RNA-sequencing (RNA-Seq) is a promising technique to resolve these questions, the bioinformatics tools to identify associated gene cascades from RNA-Seq data remain inadequate. To overcome these limitations, we developed Gene Cascade Finder (GCF) as a novel tool for building gene cascades by comparison of mutant and wild-type RNA-Seq data along with integrated information of protein-protein interactions, expression timing, and domains. Application of GCF to RNA-Seq data confirmed that SPN-4 and MEX-3 regulate the canonical Wnt pathway during embryonic development. Moreover, lin-35, hsp-3, and gpa-12 were found to be involved in MEX-1-dependent neurogenesis, and MEX-3 was found to control the gene cascade promoting neurogenesis through lin-35 and apl-1. Thus, GCF could be a useful tool for building gene cascades from RNA-Seq data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*
  • Genomics / methods*
  • Neurogenesis
  • Protein Interaction Maps*
  • Software*


  • Caenorhabditis elegans Proteins

Grants and funding

This study was supported by MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1511028) to Dr. Masahiro Ito. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.