Computational methods for analyzing and modeling genome structure and organization

Wiley Interdiscip Rev Syst Biol Med. 2019 Jan;11(1):e1435. doi: 10.1002/wsbm.1435. Epub 2018 Jul 18.

Abstract

Recent advances in chromosome conformation capture technologies have led to the discovery of previously unappreciated structural features of chromatin. Computational analysis has been critical in detecting these features and thereby helping to uncover the building blocks of genome architecture. Algorithms are being developed to integrate these architectural features to construct better three-dimensional (3D) models of the genome. These computational methods have revealed the importance of 3D genome organization to essential biological processes. In this article, we review the state of the art in analytic and modeling techniques with a focus on their application to answering various biological questions related to chromatin structure. We summarize the limitations of these computational techniques and suggest future directions, including the importance of incorporating multiple sources of experimental data in building a more comprehensive model of the genome. This article is categorized under: Analytical and Computational Methods > Computational Methods Laboratory Methods and Technologies > Genetic/Genomic Methods Models of Systems Properties and Processes > Mechanistic Models.

Keywords: 3D genome modeling; chromosome architecture; computational methods; reviews.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Computational Biology*
  • Embryo, Mammalian / embryology*
  • Embryonic Development / physiology*
  • Embryonic Germ Cells / cytology
  • Embryonic Germ Cells / metabolism*
  • Genome / physiology*
  • Mice
  • Models, Biological*
  • Transcription, Genetic / physiology