Biophysically motivated regulatory network inference: Progress and prospects

Tarmo Äijö, Richard Bonneau

Research output: Contribution to journalReview articlepeer-review

Abstract

Thanks to the confluence of genomic technology and computational developments, the possibility of network inference methods that automatically learn large comprehensive models of cellular regulation is closer than ever. This perspective focuses on enumerating the elements of computational strategies that, when coupled to appropriate experimental designs, can lead to accurate large-scale models of chromatin state and transcriptional regulatory structure and dynamics. We highlight 4 research questions that require further investigation in order to make progress in network inference: (1) using overall constraints on network structure such as sparsity, (2) use of informative priors and data integration to constrain individual model parameters, (3) estimation of latent regulatory factor activity under varying cell conditions, and (4) new methods for learning and modeling regulatory factor interactions. We conclude that methods combining advances in these 4 categories of required effort with new genomic technologies will result in biophysically motivated dynamic genome-wide regulatory network models for several of the best-studied organisms and cell types.

Original languageEnglish (US)
Pages (from-to)62-77
Number of pages16
JournalHuman Heredity
Volume81
Issue number2
DOIs
StatePublished - Jan 1 2017

Keywords

  • Chromatin state
  • Constraints
  • Factor activity
  • Informative priors
  • Regulatory network inference

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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