Connecting genotype to phenotype in the era of high-throughput sequencing

Document Type

Article

Publication Date

10-2011

Publication Source

Biochimica et Biophysica Acta - General Subjects

Volume Number

1810

Issue Number

10

First Page

967

Last Page

977

Publisher

Elsevier Science BV

ISSN

0304-4165

Comments

Article co-authored by 19 additional non-Hope College authors from 5 other institutions.

Abstract

Background: The development of next generation sequencing technology is rapidly changing the face of the genome annotation and analysis field. One of the primary uses for genome sequence data is to improve our understanding and prediction of phenotypes for microbes and microbial communities, but the technologies for predicting phenotypes must keep pace with the new sequences emerging. Scope of review: This review presents an integrated view of the methods and technologies used in the inference of phenotypes for microbes and microbial communities based on genomic and metagenomic data. Given the breadth of this topic, we place special focus on the resources available within the SEED Project. We discuss the two steps involved in connecting genotype to phenotype: sequence annotation, and phenotype inference, and we highlight the challenges in each of these steps when dealing with both single genome and metagenome data. Major conclusions: This integrated view of the genotype-to-phenotype problem highlights the importance of a controlled ontology in the annotation of genomic data, as this benefits subsequent phenotype inference and metagenome annotation. We also note the importance of expanding the set of reference genomes to improve the annotation of all sequence data, and we highlight metagenome assembly as a potential new source for complete genomes. Finally, we find that phenotype inference, particularly from metabolic models, generates predictions that can be validated and reconciled to improve annotations. General significance: This review presents the first look at the challenges and opportunities associated with the inference of phenotype from genotype during the next generation sequencing revolution. This article is part of a Special Issue entitled: SystemsBiology of Microorganisms. Published by Elsevier BM.

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