Systems approach to refining genome annotation.

TitleSystems approach to refining genome annotation.
Publication TypeJournal Article
Year of Publication2006
AuthorsReed JL, Patel TR, Chen KH, Joyce AR, Applebee KM, Herring CD, Bui OT, Knight EM, Fong S, Palsson BØ
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue46
Pagination17480-4
PubMed Date2006 Nov 14
ISSN0027-8424
KeywordsBiological Transport, Carbon, Cell Proliferation, Computational Biology, Computer Simulation, Escherichia coli, Genome, Bacterial, Malates, Open Reading Frames, Sugar Acids, Thymidine
Abstract

Genome-scale models of Escherichia coli K-12 MG1655 metabolism have been able to predict growth phenotypes in most, but not all, defined growth environments. Here we introduce the use of an optimization-based algorithm that predicts the missing reactions that are required to reconcile computation and experiment when they disagree. The computer-generated hypotheses for missing reactions were verified experimentally in five cases, leading to the functional assignment of eight ORFs (yjjLMN, yeaTU, dctA, idnT, and putP) with two new enzymatic activities and four transport functions. This study thus demonstrates the use of systems analysis to discover metabolic and transport functions and their genetic basis by a combination of experimental and computational approaches.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID17088549

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