Approaches to Computational Strain Design in the Multiomics Era

Peter St. John, Yannick Bomble

Research output: Contribution to journalArticlepeer-review

17 Scopus Citations

Abstract

Modern omics analyses are able to effectively characterize the genetic, regulatory, and metabolic phenotypes of engineered microbes, yet designing genetic interventions to achieve a desired phenotype remains challenging. With recent developments in genetic engineering techniques, timelines associated with building and testing strain designs have been greatly reduced, allowing for the first time an efficient closed loop iteration between experiment and analysis. However, the scale and complexity associated with multi-omics datasets complicates manual biological reasoning about the mechanisms driving phenotypic changes. Computational techniques therefore form a critical part of the Design-Build-Test-Learn (DBTL) cycle in metabolic engineering. Traditional statistical approaches can reduce the dimensionality of these datasets and identify common motifs among high-performing strains. While successful in many studies, these methods do not take full advantage of known connections between genes, proteins, and metabolic networks. There is therefore a growing interest in model-aided design, in which modeling frameworks from systems biology are used to integrate experimental data and generate effective and non-intuitive design predictions. In this mini-review, we discuss recent progress and challenges in this field. In particular, we compare methods augmenting flux balance analysis with additional constraints from fluxomic, genomic, and metabolomic datasets and methods employing kinetic representations of individual metabolic reactions, and machine learning. We conclude with a discussion of potential future directions for improving strain design predictions in the omics era and remaining experimental and computational hurdles.

Original languageAmerican English
Article number597
Number of pages7
JournalFrontiers in Microbiology
Volume10
Issue numberAPR
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 St. John and Bomble. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

NREL Publication Number

  • NREL/JA-2700-73411

Keywords

  • Constraint-based methods
  • Kinetic metabolic models
  • Machine learning
  • Multiomics
  • Strain engineering

Fingerprint

Dive into the research topics of 'Approaches to Computational Strain Design in the Multiomics Era'. Together they form a unique fingerprint.

Cite this