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Computational prediction of human metabolic pathways from the complete human genome.

Genome biology | Jan 11, 2005

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 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.

Pubmed ID: 15642094 RIS Download

Mesh terms: Arabidopsis | Computational Biology | Enzymes | Escherichia coli | Genome, Bacterial | Genome, Human | Genome, Plant | Humans | Internet | Metabolism | Nutritional Physiological Phenomena | Open Reading Frames

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EcoCyc

Database for the bacterium Escherichia coli K-12 MG1655, the EcoCyc project performs literature-based curation of the entire genome, and of transcriptional regulation, transporters, and metabolic pathways. The long-term goal of the project is to describe the molecular catalog of the E. coli cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of E. coli. EcoCyc is an electronic reference source for E. coli biologists, and for biologists who work with related microorganisms.

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Reactome

Collection of pathways and pathway annotations. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways (signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism) . Provides website to navigate pathway knowledge and a suite of data analysis tools to support the pathway-based analysis of complex experimental and computational data sets.

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HumanCyc: Encyclopedia of Homo sapiens Genes and Metabolism

The HumanCyc database describes human metabolic pathways and the human genome. By presenting metabolic pathways as an organizing framework for the human genome, HumanCyc provides the user with an extended dimension for functional analysis of Homo sapiens at the genomic level. A computational pathway analysis of the human genome assigned human enzymes to predicted metabolic pathways. Pathway assignments place genes in their larger biological context, and are a necessary step toward quantitative modeling of metabolism. HumanCyc contains the complete genome sequence of Homo sapiens, as presented in Build 31. Data on the human genome from Ensembl, LocusLink and GenBank were carefully merged to create a minimally redundant human gene set to serve as an input to SRI''s PathoLogic software, which generated the database and predicted Homo sapiens metabolic pathways from functional information contained in the genome''s annotation. SRI did not re-annotate the genome, but worked with the gene function assignments in Ensembl, LocusLink, and GenBank. The resulting pathway/genome database (PGDB) includes information on 28,783 genes, their products and the metabolic reactions and pathways they catalyze. Also included are many links to other databases and publications. The Pathway Tools software/database bundle includes HumanCyc and the Pathway Tools software suite and is available under license. This form of HumanCyc is faster and more powerful than the Web version.

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Plant enzymes and biochemical pathways database

The Plant Metabolic Network (PMN) is a collaborative project among databases and biochemists with a common goal to build a broad network of plant metabolic pathway databases. A central feature of the PMN is PlantCyc, a comprehensive plant biochemical pathway database, containing curated information from the literature and computational analyses about the genes, enzymes, compounds, reactions, and pathways involved in primary and secondary metabolism. The central goal of the Plant Metabolic Network (PMN) is to bring together biochemical pathway databases and research communities focused on plant metabolism. PMN will generate an infrastructure for drawing together diverse sources of plant metabolism information.

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