Fusion of single-cell transcriptome and DNA-binding data, for genomic network inference in cortical development

BMC Bioinformatics. 2021 Jun 4;22(1):301. doi: 10.1186/s12859-021-04201-9.

Abstract

Background: Network models are well-established as very useful computational-statistical tools in cell biology. However, a genomic network model based only on gene expression data can, by definition, only infer gene co-expression networks. Hence, in order to infer gene regulatory patterns, it is necessary to also include data related to binding of regulatory factors to DNA.

Results: We propose a new dynamic genomic network model, for inferring patterns of genomic regulatory influence in dynamic processes such as development. Our model fuses experiment-specific gene expression data with publicly available DNA-binding data. The method we propose is computationally efficient, and can be applied to genome-wide data with tens of thousands of transcripts. Thus, our method is well suited for use as an exploratory tool for genome-wide data. We apply our method to data from human fetal cortical development, and our findings confirm genomic regulatory patterns which are recognised as being fundamental to neuronal development.

Conclusions: Our method provides a mathematical/computational toolbox which, when coupled with targeted experiments, will reveal and confirm important new functional genomic regulatory processes in mammalian development.

Keywords: Cortical development; Gene regulatory networks; Single-cell RNA-seq.

MeSH terms

  • Animals
  • Computational Biology
  • Gene Regulatory Networks
  • Genome
  • Genomics*
  • Humans
  • Transcriptome*