{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:04:12Z","timestamp":1776326652670,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,12,8]],"date-time":"2019-12-08T00:00:00Z","timestamp":1575763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM075742"],"award-info":[{"award-number":["GM075742"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM080746"],"award-info":[{"award-number":["GM080746"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM077678"],"award-info":[{"award-number":["GM077678"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability<\/jats:title>\n                  <jats:p>The software is free for academic use; a fee is required for commercial use. See http:\/\/pathwaytools.com.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Contact<\/jats:title>\n                  <jats:p>pkarp@ai.sri.com<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Briefings in Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bib\/bbz104","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T11:27:23Z","timestamp":1564054043000},"page":"109-126","source":"Crossref","is-referenced-by-count":202,"title":["Pathway Tools version 23.0 update: software for pathway\/genome informatics and systems biology"],"prefix":"10.1093","volume":"22","author":[{"given":"Peter D","family":"Karp","sequence":"first","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Peter E","family":"Midford","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Richard","family":"Billington","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Anamika","family":"Kothari","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Markus","family":"Krummenacker","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Mario","family":"Latendresse","sequence":"additional","affiliation":[{"name":"Artificial Intelligence Center, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Wai Kit","family":"Ong","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Pallavi","family":"Subhraveti","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Ron","family":"Caspi","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Carol","family":"Fulcher","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Ingrid M","family":"Keseler","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]},{"given":"Suzanne M","family":"Paley","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Group, SRI International, Menlo Park, CA 94025, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,12,8]]},"reference":[{"key":"2021092107223837100_ref1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/bib\/bbx085","article-title":"The BioCyc collection of microbial genomes and metabolic pathways","volume":"20","author":"Karp","year":"2017","journal-title":"Briefings in Bioinformatics"},{"key":"2021092107223837100_ref2","first-page":"1","volume-title":"Pathway Tools version 19.0: Integrated software for pathway\/genome informatics and systems biology. arXiv","author":"Karp","year":"2015"},{"issue":"1","key":"2021092107223837100_ref3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2105-5-76","article-title":"A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases","volume":"5","author":"Green","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2021092107223837100_ref4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijfoodmicro.2018.05.017","article-title":"Metagenomic and metatranscriptomic analysis of the microbial community in swiss-type maasdam cheese during ripening","volume":"281","author":"Duru","year":"2018","journal-title":"Int J Food Microbiol"},{"issue":"13","key":"2021092107223837100_ref5","doi-asserted-by":"crossref","first-page":"e00554-18","DOI":"10.1128\/AEM.00554-18","article-title":"Food spoilage-associated leuconostoc, lactococcus, and lactobacillus species display different survival strategies in response to competition","volume":"84","author":"Andreevskaya","year":"2018","journal-title":"Appl Environ Microbiol"},{"issue":"8","key":"2021092107223837100_ref6","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1099\/mic.0.000473","article-title":"Systems and synthetic biology perspective of the versatile plant-pathogenic and polysaccharide-producing bacterium xanthomonas campestris","volume":"163","author":"Schatschneider","year":"2017","journal-title":"Microbiology-SGM"},{"key":"2021092107223837100_ref7","doi-asserted-by":"crossref","first-page":"170035","DOI":"10.1038\/sdata.2017.35","article-title":"A geographically-diverse collection of 418 human gut microbiome pathway genome databases","volume":"4","author":"Hahn","year":"2017","journal-title":"Scientific Data"},{"issue":"1","key":"2021092107223837100_ref8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.syapm.2018.08.007","article-title":"Candidatus prosiliicoccus vernus, a spring phytoplankton bloom associated member of the flavobacteriaceae","volume":"42","author":"Francis","year":"2019","journal-title":"Syst Appl Microbiol"},{"key":"2021092107223837100_ref9","author":"Pathway\/Genome Database Websites"},{"key":"2021092107223837100_ref10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fmicb.2019.00208","article-title":"A comparison of microbial genome web portals","volume":"10","author":"Karp","year":"2019","journal-title":"Front Microbiol"},{"issue":"D1","key":"2021092107223837100_ref11","doi-asserted-by":"crossref","first-page":"D507","DOI":"10.1093\/nar\/gkw929","article-title":"IMG\/M: integrated genome and metagenome comparative data analysis system","volume":"45","author":"Chen","year":"2017","journal-title":"Nuc Acids Res"},{"issue":"7","key":"2021092107223837100_ref12","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nbt.4163","article-title":"KBase: the United States Department of Energy Systems Biology Knowledgebase","volume":"36","author":"Arkin","year":"2018","journal-title":"Nat Biotechnol"},{"issue":"D1","key":"2021092107223837100_ref13","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nuc Acids Res"},{"issue":"Database issue","key":"2021092107223837100_ref14","doi-asserted-by":"crossref","first-page":"D581","DOI":"10.1093\/nar\/gkt1099","article-title":"PATRIC, the bacterial bioinformatics database and analysis resource","volume":"42","author":"Wattam","year":"2014","journal-title":"Nuc Acids Res"},{"issue":"1","key":"2021092107223837100_ref15","doi-asserted-by":"crossref","first-page":"D802","DOI":"10.1093\/nar\/gkx1011","article-title":"Ensembl genomes 2018: an integrated omics infrastructure for non-vertebrate species","volume":"46","author":"Kersey","year":"2018","journal-title":"Nuc Acids Res"},{"key":"2021092107223837100_ref16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40168-016-0168-z","article-title":"The metagenomics and metadesign of the subways and urban biomes (metasub) international consortium inaugural meeting report","volume":"4","author":"The MetaSUB International Consortium","year":"2016","journal-title":"Microbiome"},{"key":"2021092107223837100_ref17","first-page":"bax086","article-title":"Update notifications for the BioCyc collection of databases","author":"Paley","year":"2017","journal-title":"Database"},{"key":"2021092107223837100_ref18","author":"BioCyc Web Services"},{"key":"2021092107223837100_ref19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s40168-019-0706-6","article-title":"Metabolic route computation in organism communities","volume":"7","author":"Krummenacker","year":"2019","journal-title":"Microbiome"},{"key":"2021092107223837100_ref20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41540-019-0087-2","article-title":"Differential metabolic activity and discovery of therapeutic targets using summarized metabolic pathway models","volume":"5","author":"\u00c7ubuk","year":"2019","journal-title":"npj Systems Biology and Applications"},{"issue":"5","key":"2021092107223837100_ref21","first-page":"1363","article-title":"P-Hydroxyphenylacetate decarboxylase from Clostridium difficile","volume":"268","author":"Selmer","year":"2001","journal-title":"A novel glycyl radical enzyme catalysing the formation of p-cresol Eur J Biochem"},{"issue":"3","key":"2021092107223837100_ref22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4056\/sigs.1794338","article-title":"The pathway tools pathway prediction algorithm","volume":"5","author":"Karp","year":"2011","journal-title":"Stand Genomic Sci"},{"key":"2021092107223837100_ref23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1471-2105-11-15","article-title":"Machine learning methods for metabolic pathway prediction","volume":"11","author":"Dale","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2021092107223837100_ref24","author":"SCIP Software Home Page"},{"key":"2021092107223837100_ref25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12859-018-2050-4","article-title":"Evaluation of reaction gap-filling accuracy by randomization","volume":"19","author":"Latendresse","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"2021092107223837100_ref26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1752-0509-8-79","article-title":"A genome-scale metabolic flux model of E. coli K\u201312 derived from the EcoCyc database","volume":"8","author":"Weaver","year":"2014","journal-title":"BMC Syst Biol"},{"key":"2021092107223837100_ref27","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx910","article-title":"The Omics dashboard for interactive exploration of gene-expression data","author":"Paley","year":"2017","journal-title":"Nuc Acids Res"},{"issue":"1","key":"2021092107223837100_ref28","article-title":"The systems biology markup language (sbml): language specification for level 3 version 2 core","volume":"15","author":"Hucka","year":"2018","journal-title":"J Integr Bioinform"},{"issue":"3","key":"2021092107223837100_ref29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/genes8030090","article-title":"Rapid sampling of Escherichia coli after changing oxygen conditions reveals transcriptional dynamics","volume":"8","author":"von Wulffen","year":"2017","journal-title":"Genes (Basel)"},{"issue":"5","key":"2021092107223837100_ref30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3390\/metabo9050088","article-title":"Using pathway covering to explore connections among metabolites","volume":"9","author":"Midford","year":"2019","journal-title":"Metabolites"},{"key":"2021092107223837100_ref31","doi-asserted-by":"crossref","first-page":"D463","DOI":"10.1093\/nar\/gkv1042","article-title":"Metabolomics workbench: an international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools","volume":"44","author":"Sud","year":"2015","journal-title":"Nuc Acids Res"},{"issue":"1","key":"2021092107223837100_ref32","doi-asserted-by":"crossref","first-page":"907","DOI":"10.15252\/msb.20167150","article-title":"Genome-wide landscape of gene-metabolome associations in Escherichia coli","volume":"13","author":"Fuhrer","year":"2017","journal-title":"Mol Syst Biol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/1\/109\/40418534\/bbz104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/1\/109\/40418534\/bbz104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T07:23:28Z","timestamp":1632209008000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/22\/1\/109\/5669859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,8]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,18]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbz104","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1]]},"published":{"date-parts":[[2019,12,8]]}}}