Computational prediction of human metabolic pathways from the complete human genome

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We present a computational pathway analysis of the human genome that assigns enzymes encoded therein to predicted metabolic pathways. Pathway assignments place genes in their larger biological context, and are a necessary first step toward quantitative modeling of metabolism. Results Our analysis assigns 2,709 human enzymes to 896 bioreactions; 622 of the enzymes are assigned roles in 135 predicted metabolic pathways. The predicted pathways closely match the known nutritional requirements of humans. This analysis identifies probable omissions in the human genome annotation in the form of 203 pathway holes (missing enzymes within the predicted pathways). We have identified putative genes to fill 25 of these holes. The predicted human metabolic map is described by a Pathway/Genome Database called HumanCyc, which is available at http://HumanCyc.org/ . We describe the generation of HumanCyc, and present an analysis of the human metabolic map. For example, we compare the predicted human metabolic pathway complement to the pathways of Escherichia coli and Arabidopsis thaliana and identify 35 pathways that are shared among all three organisms. Conclusions Our analysis elucidates a significant portion of the human metabolic map, and also indicates probable unidentified genes in the genome. HumanCyc provides a genome-based view of human nutrition that associates the essential dietary requirements of humans with a set of metabolic pathways whose existence is supported by the human genome. The database places many human genes in a pathway context, thereby facilitating analysis of gene expression, proteomics, and metabolomics datasets through a publicly available online tool called the Omics Viewer.

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Published 01 January 2004
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2eRVt0o1,ssuecleArti2R0m4oerlal.emuI,6Open Access Research Computational prediction of human metabolic pathways from the complete human genome *‡ ** † Pedro Romero, Jonathan Wagg, Michelle L Green, Dale Kaiser, * * Markus Krummenackerand Peter D Karp
* † Addresses: BioinformaticsResearch Group, SRI International, 333 Ravenswood Ave, Menlo Park, CA 94025, USA.Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.Current address: School of Informatics, Center for Computational Biology and Bioinformatics, Indiana University - Purdue University Indianapolis, 714 N Senate Ave, Indianapolis, IN 46202, USA.
Correspondence: Peter D Karp. E-mail: pkarp@ai.sri.com
Published: 22 December 2004 GenomeBiology2004,6:R2 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2004/6/1/R2
Received: 25 June 2004 Revised: 11 October 2004 Accepted: 2 December 2004
© 2004 Romeroet al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. <bHopul>imcAapcnaothmwetpatobilcapp.ysaitsuThnoitasrpylislysvoaniahawyrpicedttyawhnaidosensofatghenhoumea-bnagseesinmodviuhhafotewdernttusnerneampit<s/enm.yizonesngisps>aneoceddybtehgenometopredictmde-ate
Abstract Background:We present a computational pathway analysis of the human genome that assigns enzymes encoded therein to predicted metabolic pathways. Pathway assignments place genes in their larger biological context, and are a necessary first step toward quantitative modeling of metabolism.
Results:Our analysis assigns 2,709 human enzymes to 896 bioreactions; 622 of the enzymes are assigned roles in 135 predicted metabolic pathways. The predicted pathways closely match the known nutritional requirements of humans. This analysis identifies probable omissions in the human genome annotation in the form of 203 pathway holes (missing enzymes within the predicted pathways). We have identified putative genes to fill 25 of these holes. The predicted human metabolic map is described by a Pathway/Genome Database called HumanCyc, which is available at http://HumanCyc.org/. We describe the generation of HumanCyc, and present an analysis of the human metabolic map. For example, we compare the predicted human metabolic pathway complement to the pathways ofEscherichia coliandArabidopsis thalianaand identify 35 pathways that are shared among all three organisms.
Conclusions:Our analysis elucidates a significant portion of the human metabolic map, and also indicates probable unidentified genes in the genome. HumanCyc provides a genome-based view of human nutrition that associates the essential dietary requirements of humans with a set of metabolic pathways whose existence is supported by the human genome. The database places many human genes in a pathway context, thereby facilitating analysis of gene expression, proteomics, and metabolomics datasets through a publicly available online tool called the Omics Viewer.
GenomeBiology2004,6:R2