{"id":"https://openalex.org/W4220889857","doi":"https://doi.org/10.1371/journal.pcbi.1009831","title":"Isotope-assisted metabolic flux analysis as an equality-constrained nonlinear program for improved scalability and robustness","display_name":"Isotope-assisted metabolic flux analysis as an equality-constrained nonlinear program for improved scalability and robustness","publication_year":2022,"publication_date":"2022-03-24","ids":{"openalex":"https://openalex.org/W4220889857","doi":"https://doi.org/10.1371/journal.pcbi.1009831","pmid":"https://pubmed.ncbi.nlm.nih.gov/35324890"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1009831","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1009831","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009831&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009831&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5045709200","display_name":"Daniel J. Lugar","orcid":"https://orcid.org/0000-0002-0943-9066"},"institutions":[{"id":"https://openalex.org/I66946132","display_name":"University of Maryland, College Park","ror":"https://ror.org/047s2c258","country_code":"US","type":"education","lineage":["https://openalex.org/I66946132"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel J. Lugar","raw_affiliation_strings":["Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States of America"],"affiliations":[{"raw_affiliation_string":"Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States of America","institution_ids":["https://openalex.org/I66946132"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5059288039","display_name":"Ganesh Sriram","orcid":"https://orcid.org/0000-0002-6303-1328"},"institutions":[{"id":"https://openalex.org/I66946132","display_name":"University of Maryland, College Park","ror":"https://ror.org/047s2c258","country_code":"US","type":"education","lineage":["https://openalex.org/I66946132"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Ganesh Sriram","raw_affiliation_strings":["Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States of America"],"affiliations":[{"raw_affiliation_string":"Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States of America","institution_ids":["https://openalex.org/I66946132"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5059288039"],"corresponding_institution_ids":["https://openalex.org/I66946132"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":0.9548,"has_fulltext":true,"cited_by_count":11,"citation_normalized_percentile":{"value":0.72496816,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":98},"biblio":{"volume":"18","issue":"3","first_page":"e1009831","last_page":"e1009831"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10932","display_name":"Microbial Metabolic Engineering and Bioproduction","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10932","display_name":"Microbial Metabolic Engineering and Bioproduction","score":0.9998999834060669,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10791","display_name":"Advanced Control Systems Optimization","score":0.9987000226974487,"subfield":{"id":"https://openalex.org/subfields/2207","display_name":"Control and Systems Engineering"},"field":{"id":"https://openalex.org/fields/22","display_name":"Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10621","display_name":"Gene Regulatory Network Analysis","score":0.9955999851226807,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/robustness","display_name":"Robustness (evolution)","score":0.7484384775161743},{"id":"https://openalex.org/keywords/scalability","display_name":"Scalability","score":0.6837470531463623},{"id":"https://openalex.org/keywords/nonlinear-system","display_name":"Nonlinear system","score":0.5748742818832397},{"id":"https://openalex.org/keywords/flux","display_name":"Flux (metallurgy)","score":0.5308431386947632},{"id":"https://openalex.org/keywords/metabolic-flux-analysis","display_name":"Metabolic flux analysis","score":0.47920259833335876},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.4523530602455139},{"id":"https://openalex.org/keywords/isotope","display_name":"Isotope","score":0.43321698904037476},{"id":"https://openalex.org/keywords/biological-system","display_name":"Biological system","score":0.42954036593437195},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.39715954661369324},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.36030352115631104},{"id":"https://openalex.org/keywords/bioinformatics","display_name":"Bioinformatics","score":0.335138738155365},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.25920072197914124},{"id":"https://openalex.org/keywords/physics","display_name":"Physics","score":0.22303327918052673},{"id":"https://openalex.org/keywords/metabolism","display_name":"Metabolism","score":0.18042811751365662},{"id":"https://openalex.org/keywords/biochemistry","display_name":"Biochemistry","score":0.1649412214756012},{"id":"https://openalex.org/keywords/nuclear-physics","display_name":"Nuclear physics","score":0.08165612816810608}],"concepts":[{"id":"https://openalex.org/C63479239","wikidata":"https://www.wikidata.org/wiki/Q7353546","display_name":"Robustness (evolution)","level":3,"score":0.7484384775161743},{"id":"https://openalex.org/C48044578","wikidata":"https://www.wikidata.org/wiki/Q727490","display_name":"Scalability","level":2,"score":0.6837470531463623},{"id":"https://openalex.org/C158622935","wikidata":"https://www.wikidata.org/wiki/Q660848","display_name":"Nonlinear system","level":2,"score":0.5748742818832397},{"id":"https://openalex.org/C68709404","wikidata":"https://www.wikidata.org/wiki/Q1134475","display_name":"Flux (metallurgy)","level":2,"score":0.5308431386947632},{"id":"https://openalex.org/C160941953","wikidata":"https://www.wikidata.org/wiki/Q6822342","display_name":"Metabolic flux analysis","level":3,"score":0.47920259833335876},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4523530602455139},{"id":"https://openalex.org/C164304813","wikidata":"https://www.wikidata.org/wiki/Q25276","display_name":"Isotope","level":2,"score":0.43321698904037476},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.42954036593437195},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.39715954661369324},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.36030352115631104},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.335138738155365},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.25920072197914124},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.22303327918052673},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.18042811751365662},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1649412214756012},{"id":"https://openalex.org/C185544564","wikidata":"https://www.wikidata.org/wiki/Q81197","display_name":"Nuclear physics","level":1,"score":0.08165612816810608},{"id":"https://openalex.org/C77088390","wikidata":"https://www.wikidata.org/wiki/Q8513","display_name":"Database","level":1,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002247","descriptor_name":"Carbon Isotopes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002247","descriptor_name":"Carbon Isotopes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002247","descriptor_name":"Carbon Isotopes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007553","descriptor_name":"Isotope Labeling","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D007553","descriptor_name":"Isotope Labeling","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D007553","descriptor_name":"Isotope Labeling","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015470","descriptor_name":"Leukemia, Myeloid, Acute","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015470","descriptor_name":"Leukemia, Myeloid, Acute","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015470","descriptor_name":"Leukemia, Myeloid, Acute","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D053858","descriptor_name":"Metabolic Networks and Pathways","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053858","descriptor_name":"Metabolic Networks and Pathways","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053858","descriptor_name":"Metabolic Networks and Pathways","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D064688","descriptor_name":"Metabolic Flux Analysis","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D064688","descriptor_name":"Metabolic Flux Analysis","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D064688","descriptor_name":"Metabolic Flux Analysis","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":5,"locations":[{"id":"doi:10.1371/journal.pcbi.1009831","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1009831","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009831&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:35324890","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/35324890","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS computational biology","raw_type":null},{"id":"pmh:oai:RePEc:plo:pcbi00:1009831","is_oa":false,"landing_page_url":"https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009831","pdf_url":null,"source":{"id":"https://openalex.org/S4306401271","display_name":"RePEc: Research Papers in Economics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I77793887","host_organization_name":"Federal Reserve Bank of St. Louis","host_organization_lineage":["https://openalex.org/I77793887"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"article"},{"id":"pmh:oai:doaj.org/article:652b72dea8d74ef69a5416bf3665baf2","is_oa":true,"landing_page_url":"https://doaj.org/article/652b72dea8d74ef69a5416bf3665baf2","pdf_url":null,"source":{"id":"https://openalex.org/S112646816","display_name":"SHILAP Revista de lepidopterolog\u00eda","issn_l":"0300-5267","issn":["0300-5267","2340-4078"],"is_oa":true,"is_in_doaj":true,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 18, Iss 3, p e1009831 (2022)","raw_type":"article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8947808","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8947808","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Comput Biol","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1009831","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1009831","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009831&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G1874039297","display_name":null,"funder_award_id":"MCB-1517671","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G5745323628","display_name":"Collaborative Research: Predictive Modeling of Maize Metabolism","funder_award_id":"1517671","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G6894402473","display_name":null,"funder_award_id":"Fellowship","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G8401123137","display_name":null,"funder_award_id":"2019-67015-29412","funder_id":"https://openalex.org/F4320332299","funder_display_name":"National Institute of Food and Agriculture"},{"id":"https://openalex.org/G842482667","display_name":null,"funder_award_id":"GAANN","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G848032724","display_name":null,"funder_award_id":"Science","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G8793609731","display_name":null,"funder_award_id":"2019-15 67015-29412","funder_id":"https://openalex.org/F4320332299","funder_display_name":"National Institute of Food and Agriculture"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320306114","display_name":"U.S. Department of Agriculture","ror":"https://ror.org/01na82s61"},{"id":"https://openalex.org/F4320332299","display_name":"National Institute of Food and Agriculture","ror":"https://ror.org/05qx3fv49"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4220889857.pdf","grobid_xml":"https://content.openalex.org/works/W4220889857.grobid-xml"},"referenced_works_count":37,"referenced_works":["https://openalex.org/W128066468","https://openalex.org/W1665355332","https://openalex.org/W1738124305","https://openalex.org/W1975870669","https://openalex.org/W1976336094","https://openalex.org/W1997679574","https://openalex.org/W1997774242","https://openalex.org/W2008204246","https://openalex.org/W2011970986","https://openalex.org/W2013116502","https://openalex.org/W2014323212","https://openalex.org/W2024060531","https://openalex.org/W2029290244","https://openalex.org/W2030933109","https://openalex.org/W2039262150","https://openalex.org/W2044354987","https://openalex.org/W2048295028","https://openalex.org/W2048374178","https://openalex.org/W2059902696","https://openalex.org/W2062183865","https://openalex.org/W2066333398","https://openalex.org/W2091463279","https://openalex.org/W2134138595","https://openalex.org/W2142111857","https://openalex.org/W2148497594","https://openalex.org/W2169376598","https://openalex.org/W2221321873","https://openalex.org/W2316274763","https://openalex.org/W2321346247","https://openalex.org/W2420758288","https://openalex.org/W2475074491","https://openalex.org/W2793252115","https://openalex.org/W2806788718","https://openalex.org/W2949499968","https://openalex.org/W2952877808","https://openalex.org/W3096266289","https://openalex.org/W4214486406"],"related_works":["https://openalex.org/W3096214969","https://openalex.org/W2912883929","https://openalex.org/W2245096339","https://openalex.org/W2345428922","https://openalex.org/W3037347004","https://openalex.org/W2420406980","https://openalex.org/W2006196154","https://openalex.org/W1865446941","https://openalex.org/W2026690417","https://openalex.org/W4200244030"],"abstract_inverted_index":{"Stable":[0],"isotope-assisted":[1],"metabolic":[2,17],"flux":[3],"analysis":[4],"(MFA)":[5],"is":[6,23,102,155,176,219,243,299,348,402],"a":[7,24,116,226,302,406,437],"powerful":[8],"method":[9],"to":[10,43,78,145,245,355,369,441,452,473],"estimate":[11],"carbon":[12],"flow":[13],"and":[14,31,67,98,115,142,163,185,209,215,274,362,378,396,412,419,423,445,461,485],"partitioning":[15],"in":[16,58,150,191,338,410],"networks.":[18,147],"At":[19],"its":[20],"core,":[21],"MFA":[22,55,74,95,234,276,475],"parameter":[25,140,194],"estimation":[26,141],"problem":[27,75],"wherein":[28],"the":[29,73,88,94,99,105,112,153,173,192,206,216,233,248,272,286,289,296,308,332,339,370,375,388,399,416,427,430,443],"fluxes":[30],"metabolite":[32,263],"pool":[33],"sizes":[34],"are":[35,39,91,212],"model":[36,96,113,164,193,210,249],"parameters":[37,211],"that":[38,133,373,414,458],"estimated,":[40],"via":[41],"optimization,":[42,172],"account":[44],"for":[45,65,138,307,351,393,470,481],"measurements":[46],"of":[47,72,107,118,169,179,225,237,247,258,304,390,429,447],"steady-state":[48,273,395,422],"or":[49,266],"isotopically-nonstationary":[50,275],"isotope":[51],"labeling":[52,119,297],"patterns.":[53],"As":[54],"problems":[56,278],"advance":[57],"scale,":[59],"they":[60],"require":[61],"efficient":[62],"computational":[63],"methods":[64,204,372],"fast":[66],"robust":[68,139,365],"convergence.":[69],"The":[70,254,345],"structure":[71],"enables":[76],"it":[77],"be":[79,124,280,316,467],"cast":[80],"as":[81,104,282,478],"an":[82,128,171,252,283,320,325],"equality-constrained":[83],"nonlinear":[84],"program":[85],"(NLP),":[86],"where":[87,205],"equality":[89],"constraints":[90,256,306],"constructed":[92],"from":[93,183],"equations,":[97],"objective":[100],"function":[101],"defined":[103],"sum":[106],"squared":[108],"residuals":[109],"(SSR)":[110],"between":[111,160],"predictions":[114],"set":[117],"measurements.":[120],"This":[121,196,312],"NLP":[122,230,255,309,314,321,346,385,417,431],"can":[123],"solved":[125,281,317],"by":[126],"using":[127,310,319],"algebraic":[129,305],"modeling":[130,235],"language":[131],"(AML)":[132],"offers":[134],"state-of-the-art":[135],"optimization":[136,154,197],"solvers":[137],"superior":[143],"scalability":[144,444],"large":[146,356],"When":[148],"implemented":[149,323,337],"this":[151,186,269,384,448,459],"manner,":[152],"performed":[156],"with":[157,189,201,358,487],"no":[158],"distinction":[159],"state":[161,175,207,218,377],"variables":[162,208],"parameters.":[165],"During":[166],"each":[167,223,381],"iteration":[168,224],"such":[170,477],"system":[174,217,294,303,376],"updated":[177],"instead":[178],"being":[180],"calculated":[181],"explicitly":[182],"scratch,":[184],"occurs":[187],"concurrently":[188],"improvement":[190],"estimates.":[195],"approach":[198,386,418],"starkly":[199],"contrasts":[200],"traditional":[202],"\"shooting\"":[203],"kept":[213],"distinct":[214],"computed":[220],"afresh":[221],"during":[222],"stepwise":[227],"optimization.":[228],"Our":[229],"formulation":[231,432],"uses":[232,415],"framework":[236,347,401,460],"Wiechert":[238],"et":[239],"al.":[240],"[1],":[241],"which":[242],"amenable":[244],"incorporation":[246],"equations":[250],"into":[251,301],"NLP.":[253,284],"consist":[257],"balances":[259],"on":[260,324,433],"either":[261],"elementary":[262],"units":[264],"(EMUs)":[265],"cumomers.":[267],"In":[268,327,450],"formulation,":[270],"both":[271,394,421],"(inst-MFA)":[277],"may":[279,315],"For":[285],"inst-MFA":[287,397,439,454,472],"case,":[288],"ordinary":[290],"differential":[291],"equation":[292],"(ODE)":[293],"describing":[295],"dynamics":[298],"transcribed":[300],"collocation.":[311],"large-scale":[313],"efficiently":[318],"solver":[322,335],"AML.":[326],"our":[328,462],"implementation,":[329],"we":[330,456],"used":[331],"reduced":[333],"gradient":[334],"CONOPT,":[336],"General":[340],"Algebraic":[341],"Modeling":[342],"System":[343],"(GAMS).":[344],"particularly":[349,468],"advantageous":[350],"inst-MFA,":[352],"scaling":[353],"well":[354],"networks":[357],"many":[359],"free":[360],"parameters,":[361],"having":[363],"more":[364],"convergence":[366],"properties":[367],"compared":[368],"shooting":[371],"compute":[374],"sensitivities":[379],"at":[380],"iteration.":[382],"Additionally,":[383],"supports":[387,420],"use":[389],"tandem-MS":[391],"data":[392],"when":[398],"cumomer":[400],"used.":[403],"We":[404,425],"assembled":[405],"software,":[407,464],"eiFlux,":[408,465],"written":[409],"Python":[411],"GAMS":[413],"inst-MFA.":[424],"demonstrate":[426],"effectiveness":[428],"several":[434],"examples,":[435],"including":[436],"genome-scale":[438],"model,":[440],"highlight":[442],"robustness":[446],"approach.":[449],"addition":[451],"typical":[453],"applications,":[455],"expect":[457],"associated":[463],"will":[466],"useful":[469],"applying":[471],"complex":[474],"models,":[476],"those":[479],"developed":[480],"eukaryotes":[482],"(e.g.":[483],"algae)":[484],"co-cultures":[486],"multiple":[488],"cell":[489],"types.":[490]},"counts_by_year":[{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":1}],"updated_date":"2026-04-10T15:06:20.359241","created_date":"2025-10-10T00:00:00"}
