Analysis of genetic variation and potential applications in genome-scale metabolic modeling

Frontiers in Bioengineering and Biotechnology
João G R CardosoNikolaus Sonnenschein

Abstract

Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic variation during a long term production process may lead to significant economic losses and it is important to understand how to control this type of variation. With the emergence of next-generation sequencing technologies, genetic variation in microbial strains can now be determined on an unprecedented scale and resolution by re-sequencing thousands of strains systematically. In this article, we review challenges in the integration and analysis of large-scale re-sequencing data, present an extensive overview of bioinformatics methods for predicting the effects of genetic variants on protein function, and discuss approaches for interfacin...Continue Reading

Citations

Aug 16, 2015·Molecular Genetics and Metabolism·Diego A SalazarCarlos J Alméciga-Díaz
Dec 5, 2015·Frontiers in Bioengineering and Biotechnology·Daniel MachadoMarkus J Herrgård
Jul 19, 2019·Human Mutation·Panagiotis Katsonis, Olivier Lichtarge
May 24, 2020·Nature Communications·Erol S KavvasBernhard O Palsson
Aug 8, 2015·Briefings in Bioinformatics·Mufassra NazMartin Hofmann-Apitius
Mar 29, 2018·Biochemical Society Transactions·Martin H Rau, Ahmad A Zeidan
Sep 23, 2020·Nature Reviews. Microbiology·Xin FangBernhard O Palsson

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Methods Mentioned

BETA
gene knockout
genotyping
in silico methods
protein folding

Software Mentioned

FunSAV
MAGE
MUTE
Polyphen
PROVEAN
HANSA
PI
RELATCH
AUTO
Mutation taster

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