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Systems Approach to Refining Genome Annotation
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 an...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (46), p.17480-17484 |
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container_end_page | 17484 |
container_issue | 46 |
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container_title | Proceedings of the National Academy of Sciences - PNAS |
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creator | Reed, Jennifer L. Patel, Trina R. Chen, Keri H. Joyce, Andrew R. Applebee, Margaret K. Herring, Christopher D. Bui, Olivia T. Knight, Eric M. Fong, Stephen S. Palsson, Bernhard O. |
description | 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. |
doi_str_mv | 10.1073/pnas.0603364103 |
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subjects | Algorithms Biological Sciences Biological Transport Carbon Carbon - metabolism Cell Proliferation Complementary DNA Computational Biology Computer Simulation E coli Escherichia coli Escherichia coli - cytology Escherichia coli - genetics Escherichia coli - metabolism Genetic screening Genome, Bacterial - genetics Genomes Genomics Malates - metabolism Metabolism Modeling Open Reading Frames - genetics Phenotypes Propionates Reverse transcriptase polymerase chain reaction Studies Sugar Acids - metabolism Thymidine - metabolism |
title | Systems Approach to Refining Genome Annotation |
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