RESUMO
MOTIVATION: Biological systems function through dynamic interactions among genes and their products, regulatory circuits and metabolic networks. Our development of the Pathway Tools software was motivated by the need to construct biological knowledge resources that combine these many types of data, and that enable users to find and comprehend data of interest as quickly as possible through query and visualization tools. Further, we sought to support the development of metabolic flux models from pathway databases, and to use pathway information to leverage the interpretation of high-throughput data sets. RESULTS: In the past 4 years we have enhanced the already extensive Pathway Tools software in several respects. It can now support metabolic-model execution through the Web, it provides a more accurate gap filler for metabolic models; it supports development of models for organism communities distributed across a spatial grid; and model results may be visualized graphically. Pathway Tools supports several new omics-data analysis tools including the Omics Dashboard, multi-pathway diagrams called pathway collages, a pathway-covering algorithm for metabolomics data analysis and an algorithm for generating mechanistic explanations of multi-omics data. We have also improved the core pathway/genome databases management capabilities of the software, providing new multi-organism search tools for organism communities, improved graphics rendering, faster performance and re-designed gene and metabolite pages. AVAILABILITY: The software is free for academic use; a fee is required for commercial use. See http://pathwaytools.com. CONTACT: pkarp@ai.sri.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.
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Genômica/métodos , Metabolômica/métodos , Software/normas , Biologia de Sistemas/métodos , Animais , HumanosRESUMO
MetaCyc (MetaCyc.org) is a comprehensive reference database of metabolic pathways and enzymes from all domains of life. It contains 2749 pathways derived from more than 60 000 publications, making it the largest curated collection of metabolic pathways. The data in MetaCyc are evidence-based and richly curated, resulting in an encyclopedic reference tool for metabolism. MetaCyc is also used as a knowledge base for generating thousands of organism-specific Pathway/Genome Databases (PGDBs), which are available in BioCyc.org and other genomic portals. This article provides an update on the developments in MetaCyc during September 2017 to August 2019, up to version 23.1. Some of the topics that received intensive curation during this period include cobamides biosynthesis, sterol metabolism, fatty acid biosynthesis, lipid metabolism, carotenoid metabolism, protein glycosylation, antibiotics and cytotoxins biosynthesis, siderophore biosynthesis, bioluminescence, vitamin K metabolism, brominated compound metabolism, plant secondary metabolism and human metabolism. Other additions include modifications to the GlycanBuilder software that enable displaying glycans using symbolic representation, improved graphics and fonts for web displays, improvements in the PathoLogic component of Pathway Tools, and the optional addition of regulatory information to pathway diagrams.
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Bases de Dados Factuais , Genômica/métodos , Redes e Vias Metabólicas , Metabolômica/métodos , Software , Animais , Enzimas/genética , Enzimas/metabolismo , Humanos , Plantas/genética , Plantas/metabolismoRESUMO
BACKGROUND: The Metabolic Network Explorer is a new addition to the BioCyc.org website and the Pathway Tools software suite that supports the interactive exploration of metabolic networks. Any metabolic network visualization tool must by necessity show only a subset of all possible metabolite connections, or the results will be visually overwhelming. Existing tools, even those that purport to show an organism's full metabolic network, limit the set of displayed connections based on predefined pathways or other preselected criteria. We sought instead to provide a tool that would give the user dynamic control over which connections to follow. RESULTS: The Metabolic Network Explorer is an easy-to-use, web-based software tool that allows the user to specify a starting metabolite of interest and interactively explore its immediate metabolic neighborhood in either or both directions to any desired depth, letting the user select from the full set of connected reactions. Although, as for other tools, only a small portion of the metabolic network is visible at a time, that portion is selected by the user, based on the full reaction complement, and it is easy to switch among alternate paths of interest. The display is intuitive, customizable, and provides copious links to more detailed information pages. CONCLUSIONS: The Metabolic Network Explorer fills a gap in the set of metabolic network visualization tools and complements other modes of exploration. Its primary strengths are its ease of use, diagrams that are intuitive to biologists, and its integration with the broader corpus of data provided by a BioCyc Pathway/Genome Database.
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Redes e Vias Metabólicas , Software , InternetRESUMO
BACKGROUND: Enrichment or over-representation analysis is a common method used in bioinformatics studies of transcriptomics, metabolomics, and microbiome datasets. The key idea behind enrichment analysis is: given a set of significantly expressed genes (or metabolites), use that set to infer a smaller set of perturbed biological pathways or processes, in which those genes (or metabolites) play a role. Enrichment computations rely on collections of defined biological pathways and/or processes, which are usually drawn from pathway databases. Although practitioners of enrichment analysis take great care to employ statistical corrections (e.g., for multiple testing), they appear unaware that enrichment results are quite sensitive to the pathway definitions that the calculation uses. RESULTS: We show that alternative pathway definitions can alter enrichment p-values by up to nine orders of magnitude, whereas statistical corrections typically alter enrichment p-values by only two orders of magnitude. We present multiple examples where the smaller pathway definitions used in the EcoCyc database produces stronger enrichment p-values than the much larger pathway definitions used in the KEGG database; we demonstrate that to attain a given enrichment p-value, KEGG-based enrichment analyses require 1.3-2.0 times as many significantly expressed genes as does EcoCyc-based enrichment analyses. The large pathways in KEGG are problematic for another reason: they blur together multiple (as many as 21) biological processes. When such a KEGG pathway receives a high enrichment p-value, which of its component processes is perturbed is unclear, and thus the biological conclusions drawn from enrichment of large pathways are also in question. CONCLUSIONS: The choice of pathway database used in enrichment analyses can have a much stronger effect on the enrichment results than the statistical corrections used in these analyses.
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Biologia Computacional , Metabolômica , Bases de Dados FactuaisRESUMO
BioCyc.org is a microbial genome Web portal that combines thousands of genomes with additional information inferred by computer programs, imported from other databases and curated from the biomedical literature by biologist curators. BioCyc also provides an extensive range of query tools, visualization services and analysis software. Recent advances in BioCyc include an expansion in the content of BioCyc in terms of both the number of genomes and the types of information available for each genome; an expansion in the amount of curated content within BioCyc; and new developments in the BioCyc software tools including redesigned gene/protein pages and metabolite pages; new search tools; a new sequence-alignment tool; a new tool for visualizing groups of related metabolic pathways; and a facility called SmartTables, which enables biologists to perform analyses that previously would have required a programmer's assistance.
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Genoma Microbiano , Redes e Vias Metabólicas , Software , Biologia Computacional , Bases de Dados Genéticas , Escherichia coli/genética , Escherichia coli/metabolismo , Genômica , Internet , Modelos Biológicos , Ferramenta de BuscaRESUMO
MOTIVATION: The increasing availability of annotated genome sequences enables construction of genome-scale metabolic networks, which are useful tools for studying organisms of interest. However, due to incomplete genome annotations, draft metabolic models contain gaps that must be filled in a time-consuming process before they are usable. Optimization-based algorithms that fill these gaps have been developed, however, gap-filling algorithms show significant error rates and often introduce incorrect reactions. RESULTS: Here, we present a new gap-filling method that computes the costs of candidate gap-filling reactions from a universal reaction database (MetaCyc) based on taxonomic information. When gap-filling a metabolic model for an organism M (such as Escherichia coli), the cost for reaction R is based on the frequency with which R occurs in other organisms within the phylum of M (in this case, Proteobacteria). The assumption behind this method is that different taxonomic groups are biased toward using different metabolic reactions. Evaluation of the new gap-filler on randomly degraded variants of the EcoCyc metabolic model for E.coli showed an increase in the average F1-score to 99.0 (when using the variable weights by frequency method at the phylum level), compared to 91.0 using the previous MetaFlux gap-filler and 80.3 using a basic gap-filler. Evaluation on two other microbial metabolic models showed similar improvements. AVAILABILITY AND IMPLEMENTATION: The Pathway Tools software (including MetaFlux) is free for academic use and is available at http://pathwaytools.com. Additional code for reproducing the results presented here is available at www.ai.sri.com/pkarp/pubs/taxgap/supplementary.zip. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Software , Bases de Dados Factuais , Genoma , Redes e Vias MetabólicasRESUMO
To understand and engineer plant metabolism, we need a comprehensive and accurate annotation of all metabolic information across plant species. As a step towards this goal, we generated genome-scale metabolic pathway databases of 126 algal and plant genomes, ranging from model organisms to crops to medicinal plants (https://plantcyc.org). Of these, 104 have not been reported before. We systematically evaluated the quality of the databases, which revealed that our semi-automated validation pipeline dramatically improves the quality. We then compared the metabolic content across the 126 organisms using multiple correspondence analysis and found that Brassicaceae, Poaceae, and Chlorophyta appeared as metabolically distinct groups. To demonstrate the utility of this resource, we used recently published sorghum transcriptomics data to discover previously unreported trends of metabolism underlying drought tolerance. We also used single-cell transcriptomics data from the Arabidopsis root to infer cell type-specific metabolic pathways. This work shows the quality and quantity of our resource and demonstrates its wide-ranging utility in integrating metabolism with other areas of plant biology.
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Bases de Dados Factuais , Redes e Vias Metabólicas , Plantas/metabolismo , Viridiplantae/metabolismo , Genoma de Planta , Plantas/genéticaRESUMO
We present a rationale for expanding the presence of the Lisp family of programming languages in bioinformatics and computational biology research. Put simply, Lisp-family languages enable programmers to more quickly write programs that run faster than in other languages. Languages such as Common Lisp, Scheme and Clojure facilitate the creation of powerful and flexible software that is required for complex and rapidly evolving domains like biology. We will point out several important key features that distinguish languages of the Lisp family from other programming languages, and we will explain how these features can aid researchers in becoming more productive and creating better code. We will also show how these features make these languages ideal tools for artificial intelligence and machine learning applications. We will specifically stress the advantages of domain-specific languages (DSLs): languages that are specialized to a particular area, and thus not only facilitate easier research problem formulation, but also aid in the establishment of standards and best programming practices as applied to the specific research field at hand. DSLs are particularly easy to build in Common Lisp, the most comprehensive Lisp dialect, which is commonly referred to as the 'programmable programming language'. We are convinced that Lisp grants programmers unprecedented power to build increasingly sophisticated artificial intelligence systems that may ultimately transform machine learning and artificial intelligence research in bioinformatics and computational biology.
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Inteligência Artificial , Biologia Computacional/métodos , Linguagens de Programação , SoftwareRESUMO
MetaCyc (https://MetaCyc.org) is a comprehensive reference database of metabolic pathways and enzymes from all domains of life. It contains more than 2570 pathways derived from >54 000 publications, making it the largest curated collection of metabolic pathways. The data in MetaCyc is strictly evidence-based and richly curated, resulting in an encyclopedic reference tool for metabolism. MetaCyc is also used as a knowledge base for generating thousands of organism-specific Pathway/Genome Databases (PGDBs), which are available in the BioCyc (https://BioCyc.org) and other PGDB collections. This article provides an update on the developments in MetaCyc during the past two years, including the expansion of data and addition of new features.
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Bases de Dados Factuais , Enzimas/metabolismo , Redes e Vias Metabólicas , Animais , Archaea/metabolismo , Bactérias/metabolismo , Curadoria de Dados , Bases de Dados de Compostos Químicos , Bases de Dados de Proteínas , Humanos , Internet , Filogenia , Plantas/metabolismo , Software , Especificidade da EspécieRESUMO
BACKGROUND: High-throughput experiments can bring to light associations between genes, proteins and/or metabolites, many of which will be explainable by existing knowledge. Our aim is to speed elucidation of such explanations and, in some cases, find explanations that scientists might otherwise overlook. RESULTS: We describe the MultiOmics Explainer, a new tool within the Pathway Tools software suite that leverages what is known about an organism's metabolic and regulatory network to suggest explanations for the results of omics experiments. Querying a database such as EcoCyc, the MultiOmics Explainer searches the organism's network of metabolic reactions, transporters, cofactors, enzyme substrate-level activation and inhibition relationships, and transcriptional and translational regulation relationships to identify paths of influence among input genes, proteins and metabolites. Results are presented in a combined metabolic and regulatory diagram. We present several examples of explanations generated for associations found in the Escherichia coli literature. CONCLUSIONS: The MultiOmics Explainer is a valuable tool that helps researchers understand and interpret the results of their omics experiments in the context of what is known about an organism's metabolic and regulatory network. It showcases the rich set of computational inferences that can be drawn from a database such as EcoCyc that encodes a diverse range of biological interactions.
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Perfilação da Expressão Gênica , Metabolômica , Proteômica , Software , Bases de Dados Factuais , Bases de Dados Genéticas , Escherichia coli/genética , Escherichia coli/metabolismo , Genoma , Redes e Vias MetabólicasRESUMO
The Omics Dashboard is a software tool for interactive exploration and analysis of gene-expression datasets. The Omics Dashboard is organized as a hierarchy of cellular systems. At the highest level of the hierarchy the Dashboard contains graphical panels depicting systems such as biosynthesis, energy metabolism, regulation and central dogma. Each of those panels contains a series of X-Y plots depicting expression levels of subsystems of that panel, e.g. subsystems within the central dogma panel include transcription, translation and protein maturation and folding. The Dashboard presents a visual read-out of the expression status of cellular systems to facilitate a rapid top-down user survey of how all cellular systems are responding to a given stimulus, and to enable the user to quickly view the responses of genes within specific systems of interest. Although the Dashboard is complementary to traditional statistical methods for analysis of gene-expression data, we show how it can detect changes in gene expression that statistical techniques may overlook. We present the capabilities of the Dashboard using two case studies: the analysis of lipid production for the marine alga Thalassiosira pseudonana, and an investigation of a shift from anaerobic to aerobic growth for the bacterium Escherichia coli.
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Perfilação da Expressão Gênica/métodos , Software , Diatomáceas/genética , Diatomáceas/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Metabolismo dos LipídeosRESUMO
EcoCyc (EcoCyc.org) is a freely accessible, comprehensive database that collects and summarizes experimental data for Escherichia coli K-12, the best-studied bacterial model organism. New experimental discoveries about gene products, their function and regulation, new metabolic pathways, enzymes and cofactors are regularly added to EcoCyc. New SmartTable tools allow users to browse collections of related EcoCyc content. SmartTables can also serve as repositories for user- or curator-generated lists. EcoCyc now supports running and modifying E. coli metabolic models directly on the EcoCyc website.
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Biologia Computacional/métodos , Bases de Dados Genéticas , Escherichia coli K12/genética , Escherichia coli K12/metabolismo , Metabolismo Energético , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Redes e Vias Metabólicas , Transdução de Sinais , Software , Fatores de Transcrição/metabolismo , NavegadorRESUMO
BACKGROUND: Completion of genome-scale flux-balance models using computational reaction gap-filling is a widely used approach, but its accuracy is not well known. RESULTS: We report on computational experiments of reaction gap filling in which we generated degraded versions of the EcoCyc-20.0-GEM model by randomly removing flux-carrying reactions from a growing model. We gap-filled the degraded models and compared the resulting gap-filled models with the original model. Gap-filling was performed by the Pathway Tools MetaFlux software using its General Development Mode (GenDev) and its Fast Development Mode (FastDev). We explored 12 GenDev variants including two linear solvers (SCIP and CPLEX) for solving the Mixed Integer Linear Programming (MILP) problems for gap filling; three different sets of linear constraints were applied; and two MILP methods were implemented. We compared these 13 variants according to accuracy, speed, and amount of information returned to the user. CONCLUSIONS: We observed large variation among the performance of the 13 gap-filling variants. Although no variant was best in all dimensions, we found one variant that was fast, accurate, and returned more information to the user. Some gap-filling variants were inaccurate, producing solutions that were non-minimum or invalid (did not enable model growth). The best GenDev variant showed a best average precision of 87% and a best average recall of 61%. FastDev showed an average precision of 71% and an average recall of 59%. Thus, using the most accurate variant, approximately 13% of the gap-filled reactions were incorrect (were not the reactions removed from the model), and 39% of gap-filled reactions were not found, suggesting that curation is still an important aspect of metabolic-model development.
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Análise do Fluxo Metabólico/métodos , Modelos Biológicos , Algoritmos , Genômica , Programação Linear , SoftwareRESUMO
Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The software provides genome-informatics tools such as a genome browser, sequence alignments, a genome-variant analyzer and comparative-genomics operations. It offers metabolic-informatics tools, such as metabolic reconstruction, quantitative metabolic modeling, prediction of reaction atom mappings and metabolic route search. Pathway Tools also provides regulatory-informatics tools, such as the ability to represent and visualize a wide range of regulatory interactions. This article outlines the advances in Pathway Tools in the past 5 years. Major additions include components for metabolic modeling, metabolic route search, computation of atom mappings and estimation of compound Gibbs free energies of formation; addition of editors for signaling pathways, for genome sequences and for cellular architecture; storage of gene essentiality data and phenotype data; display of multiple alignments, and of signaling and electron-transport pathways; and development of Python and web-services application programming interfaces. Scientists around the world have created more than 9800 Pathway/Genome Databases by using Pathway Tools, many of which are curated databases for important model organisms.
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Genoma , Biologia Computacional , Genômica , Internet , Redes e Vias Metabólicas , Design de Software , Biologia de SistemasRESUMO
The MetaCyc database (MetaCyc.org) is a freely accessible comprehensive database describing metabolic pathways and enzymes from all domains of life. The majority of MetaCyc pathways are small-molecule metabolic pathways that have been experimentally determined. MetaCyc contains more than 2400 pathways derived from >46,000 publications, and is the largest curated collection of metabolic pathways. BioCyc (BioCyc.org) is a collection of 5700 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems, and pathway-hole fillers. The BioCyc website offers a variety of tools for querying and analyzing PGDBs, including Omics Viewers and tools for comparative analysis. This article provides an update of new developments in MetaCyc and BioCyc during the last two years, including addition of Gibbs free energy values for compounds and reactions; redesign of the primary gene/protein page; addition of a tool for creating diagrams containing multiple linked pathways; several new search capabilities, including searching for genes based on sequence patterns, searching for databases based on an organism's phenotypes, and a cross-organism search; and a metabolite identifier translation service.
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Bases de Dados de Compostos Químicos , Enzimas/metabolismo , Redes e Vias Metabólicas , Bases de Dados Genéticas , Transporte de Elétrons , Genoma , Internet , Redes e Vias Metabólicas/genética , SoftwareRESUMO
MOTIVATION: Metabolic modeling depends on accurately representing the cellular locations of enzyme-catalyzed and transport reactions. We sought to develop a representation of cellular compartmentation that would accurately capture cellular location information. We further sought a representation that would support automated inference of the cellular compartments present in newly sequenced organisms to speed model development, and that would enable representing the cellular compartments present in multiple cell types within a multicellular organism. RESULTS: We define the cellular architecture of a unicellular organism, or of a cell type from a multicellular organism, as the collection of cellular components it contains plus the topological relationships among those components. We developed a tool for inferring cellular architectures across many domains of life and extended our Cell Component Ontology to enable representation of the inferred architectures. We provide software for visualizing cellular architectures to verify their correctness and software for editing cellular architectures to modify or correct them. We also developed a representation that records the cellular compartment assignments of reactions with minimal duplication of information. AVAILABILITY AND IMPLEMENTATION: The Cell Component Ontology is freely available. The Pathway Tools software is freely available for academic research and is available for a fee for commercial use. CONTACT: pkarp@ai.sri.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Fenômenos Fisiológicos Celulares , Gráficos por Computador , Software , Algoritmos , Biologia Celular , Modelos TeóricosRESUMO
BACKGROUND: Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? RESULTS: We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. CONCLUSIONS: Pathway collages enable facile construction of personalized multi-pathway diagrams.
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Escherichia coli/metabolismo , Metabolômica/métodos , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Redes e Vias Metabólicas , Modelos Biológicos , SoftwareRESUMO
UNLABELLED: Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains and three-dimensional protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB) announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology 2016, Orlando, FL). CONTACT: dkovats@iscb.org or rost@in.tum.de.
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Distinções e Prêmios , Pesquisa Biomédica , Biologia Computacional , Doença pelo Vírus Ebola/virologia , Sociedades Científicas , Bases de Dados Factuais , Ebolavirus/genética , Ebolavirus/patogenicidade , Humanos , Agências InternacionaisRESUMO
The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37,000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states.
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Bases de Dados de Compostos Químicos , Enzimas/metabolismo , Redes e Vias Metabólicas , Enzimas/química , Enzimas/classificação , Ontologia Genética , Genoma , Internet , Cinética , Redes e Vias Metabólicas/genética , Polissacarídeos/metabolismo , SoftwareRESUMO
PortEco (http://porteco.org) aims to collect, curate and provide data and analysis tools to support basic biological research in Escherichia coli (and eventually other bacterial systems). PortEco is implemented as a 'virtual' model organism database that provides a single unified interface to the user, while integrating information from a variety of sources. The main focus of PortEco is to enable broad use of the growing number of high-throughput experiments available for E. coli, and to leverage community annotation through the EcoliWiki and GONUTS systems. Currently, PortEco includes curated data from hundreds of genome-wide RNA expression studies, from high-throughput phenotyping of single-gene knockouts under hundreds of annotated conditions, from chromatin immunoprecipitation experiments for tens of different DNA-binding factors and from ribosome profiling experiments that yield insights into protein expression. Conditions have been annotated with a consistent vocabulary, and data have been consistently normalized to enable users to find, compare and interpret relevant experiments. PortEco includes tools for data analysis, including clustering, enrichment analysis and exploration via genome browsers. PortEco search and data analysis tools are extensively linked to the curated gene, metabolic pathway and regulation content at its sister site, EcoCyc.