Advanced Life Sciences Program, Graduate School of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
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.
全面了解参与秀丽隐杆线虫细胞命运决定和细胞谱系分离的基因调控网络（或基因级联）是一个长期存在的挑战。尽管 RNA 测序（RNA-Seq）是解决这些问题的有前途的技术，但从 RNA-Seq 数据中识别相关基因级联的生物信息学工具仍然不足。为了克服这些限制，我们开发了 Gene Cascade Finder（GCF），这是一种通过比较突变体和野生型 RNA-Seq 数据以及蛋白质-蛋白质相互作用、表达时间和结构域的综合信息来构建基因级联的新工具。将 GCF 应用于 RNA-Seq 数据证实，SPN-4 和 MEX-3 在胚胎发育过程中调节经典 Wnt 途径。此外，发现 lin-35、hsp-3 和 gpa-12 参与 MEX-1 依赖性神经发生，并且发现 MEX-3 通过 lin-35 和 apl-1 控制促进神经发生的基因级联。因此，GCF 可以成为从 RNA-Seq 数据构建基因级联的有用工具。
