Computational prediction of human metabolic pathways from the complete human genome

By Pedro Romero, J. Wagg, M. Green, Dale Kaiser, Markus Krummenacker, Peter D. Karp. Genome Biology, 2004

558 citations recorded by the source corpus.

BackgroundWe 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.ResultsOur 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.ConclusionsOur 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0de3b348a17998b9782239ab490297fb4b8b8fc2

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In Molecular Biology

Citations in the corpus

PID: the Pathway Interaction Database (2008, unknown): “PID diﬀers from Reactome, HumanCyc and KEGG in its focus on signaling and regulatory pathways; it does not attempt to cover metabolic processes or generic mechanisms like transcription and translation (see Table 1 for a comparison of PID with other publicly accessible pathway databases).”
Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, background): “…Metabolic pathway resource http://kegg.jp Kanehisa et al., 2012 MetaCyc http://metacyc.org Caspi et al., 2012 HumanCyc http://humancyc.org Romero et al., 2005 SMPDB Small Molecule (e.g., drug) Pathway Database http://smpdb.ca Frolkis et al., 2010 HMDB Human Metabolome Database…”
ConsensusPathDB—a database for integrating human functional interaction networks (2008, background): “Currently, the database contains human functional interactions, including gene regulations, physical (protein–protein and protein-compound) interactions and biochemical (signaling and metabolic) reactions, obtained by integrating such data from 12 publicly accessible databases (referred to as source”
Network-based prediction of human tissue-specific metabolism (2008, background): “However, in reconstructing human metabolic networks, most of the previous work has focused on characterizing distinct metabolic pathway”
Pathway Commons, a web resource for biological pathway data (2010, background): “However, where source databases do maintain stable pathway records IDs, such as in the case of Reactome and HumanCyc, Pathway Commons plans to make stable pathway links available for these data sources in the future.”
The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases (2009, methodology): “Generation of precursor metabolites and energy (124) Fermentation (34) Respiration (25) Chemoautotrophic Energy Metabolism (14) Methanogenesis (12) Electron Transfer (11) TCA cycle (9) Glycolysis (6) Photosynthesis (6) Pentose Phosphate Pathways (4) Other (3) Detoxification (16) Methylglyoxal Detoxi”
The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function (2010, background): “Data sets are collected from publicly available databases, including co-expression data from Gene Expression Omnibus (GEO) (1); physical and genetic interaction data from BioGRID (2); predicted protein interaction data based on orthology from I2D (3); and pathway and molecular interaction data from ”
Expansion of the BioCyc collection of pathway/genome databases to 160 genomes (2005, background): “BioCyc contains 17 PGDBs in Tier 2, including HumanCyc (24), AgroCyc and FrantCyc (25).”
Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT (2012, methodology): “There are three generic genome-scale human metabolic networks currently available, namely Recon1 [7], the Edinburgh Human Metabolic Network (EHMN) [8] and HumanCyc [9].”
Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology (2010, background): “Animals Homo sapiens (HumanCyc) [68, 69] Mus musculus (MouseCyc) [70] Bos taurus (CattleCyc) [71, 72] Plants A.”