Boolean Network Models of Human Preimplantation Development

J Comput Biol. 2024 Jun;31(6):513-523. doi: 10.1089/cmb.2024.0517. Epub 2024 May 29.

Abstract

Single-cell transcriptomic studies of differentiating systems allow meaningful understanding, especially in human embryonic development and cell fate determination. We present an innovative method aimed at modeling these intricate processes by leveraging scRNAseq data from various human developmental stages. Our implemented method identifies pseudo-perturbations, since actual perturbations are unavailable due to ethical and technical constraints. By integrating these pseudo-perturbations with prior knowledge of gene interactions, our framework generates stage-specific Boolean networks (BNs). We apply our method to medium and late trophectoderm developmental stages and identify 20 pseudo-perturbations required to infer BNs. The resulting BN families delineate distinct regulatory mechanisms, enabling the differentiation between these developmental stages. We show that our program outperforms existing pseudo-perturbation identification tool. Our framework contributes to comprehending human developmental processes and holds potential applicability to diverse developmental stages and other research scenarios.

Keywords: Answer Set Programming; Boolean networks; human embryonic development; scRNAseq; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blastocyst / metabolism
  • Cell Differentiation / genetics
  • Computational Biology / methods
  • Embryonic Development* / genetics
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Humans
  • Single-Cell Analysis / methods
  • Transcriptome