{"id":"https://openalex.org/W124488796","doi":null,"title":"Large-scale metabolic flux analysis for mammalian cells: a systematic progression from model conception to model reduction to experimental design","display_name":"Large-scale metabolic flux analysis for mammalian cells: a systematic progression from model conception to model reduction to experimental design","publication_year":2009,"publication_date":"2009-11-01","ids":{"openalex":"https://openalex.org/W124488796","mag":"124488796"},"language":"en","primary_location":{"id":"mag:124488796","doi":null,"is_oa":false,"landing_page_url":"https://espace.library.uq.edu.au/view/UQ:204905","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null},"volume":null,"type":"article","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5030141585","display_name":"Lake\u2010Ee Quek","orcid":"https://orcid.org/0000-0002-9313-8740","observed_orcids":["https://orcid.org/0000-0002-9313-8740"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Lake\u2010Ee Quek","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-9313-8740","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5030141585"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.1099,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.42100527,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10932","display_name":"Microbial Metabolic Engineering and Bioproduction","score":0.9951000213623047,"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":0.9951000213623047,"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/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.002099999925121665,"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/T10621","display_name":"Gene Regulatory Network Analysis","score":0.00139999995008111,"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/metabolic-flux-analysis","display_name":"metabolic flux analysis","score":0.9150000214576721},{"id":"https://openalex.org/keywords/cho-cells","display_name":"CHO cells","score":0.7009999752044678},{"id":"https://openalex.org/keywords/hybridoma-culture","display_name":"hybridoma cell culture","score":0.8119999766349792},{"id":"https://openalex.org/keywords/13c-metabolic-flux-analysis","display_name":"13C metabolic flux analysis","score":0.9100000262260437},{"id":"https://openalex.org/keywords/stoichiometric-metabolic-model","display_name":"stoichiometric metabolic model","score":0.6690000295639038},{"id":"https://openalex.org/keywords/model-reduction","display_name":"model reduction","score":0.8539999723434448},{"id":"https://openalex.org/keywords/constraint-based-analysis","display_name":"constraint-based analysis","score":0.6620000004768372},{"id":"https://openalex.org/keywords/central-carbon-metabolism","display_name":"central carbon metabolism","score":0.6489999890327454},{"id":"https://openalex.org/keywords/fluxomics","display_name":"fluxomics","score":0.4169999957084656},{"id":"https://openalex.org/keywords/metabolic-engineering","display_name":"metabolic engineering","score":0.5540000200271606},{"id":"https://openalex.org/keywords/recombinant-protein-expression","display_name":"recombinant protein expression","score":0.8859999775886536},{"id":"https://openalex.org/keywords/experimental-design","display_name":"experimental design","score":0.47600001096725464},{"id":"https://openalex.org/keywords/irreversibility-constraints","display_name":"irreversibility constraints","score":0.5830000042915344}],"concepts":[{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.7139723896980286},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.5906129479408264},{"id":"https://openalex.org/C160941953","wikidata":"https://www.wikidata.org/wiki/Q6822342","display_name":"Metabolic flux analysis","level":3,"score":0.5758167505264282},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.5732184052467346},{"id":"https://openalex.org/C68709404","wikidata":"https://www.wikidata.org/wiki/Q1134475","display_name":"Flux (metallurgy)","level":2,"score":0.571792721748352},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5660297870635986},{"id":"https://openalex.org/C2781047461","wikidata":"https://www.wikidata.org/wiki/Q679692","display_name":"Biopharmaceutical","level":2,"score":0.5366377830505371},{"id":"https://openalex.org/C6350086","wikidata":"https://www.wikidata.org/wiki/Q6822347","display_name":"Metabolic engineering","level":3,"score":0.4954298734664917},{"id":"https://openalex.org/C2994212657","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Cellular metabolism","level":3,"score":0.4753793776035309},{"id":"https://openalex.org/C183696295","wikidata":"https://www.wikidata.org/wiki/Q2487696","display_name":"Biochemical engineering","level":1,"score":0.47495126724243164},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.44034281373023987},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.43249309062957764},{"id":"https://openalex.org/C167091322","wikidata":"https://www.wikidata.org/wiki/Q5463029","display_name":"Flux balance analysis","level":2,"score":0.4287063181400299},{"id":"https://openalex.org/C2778755073","wikidata":"https://www.wikidata.org/wiki/Q10858537","display_name":"Scale (ratio)","level":2,"score":0.4133002460002899},{"id":"https://openalex.org/C2991704936","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Cell metabolism","level":3,"score":0.41221633553504944},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.23554518818855286},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.20880860090255737},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.205699622631073},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.19335687160491943},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.17000603675842285},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.15339788794517517},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.11813965439796448},{"id":"https://openalex.org/C62520636","wikidata":"https://www.wikidata.org/wiki/Q944","display_name":"Quantum mechanics","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/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0},{"id":"https://openalex.org/C121332964","wikidata":"https://www.wikidata.org/wiki/Q413","display_name":"Physics","level":0,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"mag:124488796","doi":null,"is_oa":false,"landing_page_url":"https://espace.library.uq.edu.au/view/UQ:204905","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W145337578","https://openalex.org/W1583997234","https://openalex.org/W2991464353","https://openalex.org/W2293230577","https://openalex.org/W1579192815","https://openalex.org/W1907305170","https://openalex.org/W2025083491","https://openalex.org/W2115574341","https://openalex.org/W1181425224","https://openalex.org/W2512776866"],"abstract_inverted_index":{"Recombinant":[0],"protein":[1],"production":[2],"by":[3,518,535,650,722],"mammalian":[4,395,441,717,850,876],"cells":[5,843],"is":[6,86,151,186,211,231,334,453,794],"a":[7,63,82,113,142,196,199,223,417,433,471,600,726,795,798,811,857,872],"core":[8],"component":[9],"of":[10,51,60,102,116,126,167,173,189,222,254,263,320,340,350,355,381,386,402,432,450,473,506,512,525,558,585,592,597,614,654,660,666,725,733,739,746,754,805,836,849,856],"today\u2019s":[11],"multi-billion":[12],"dollar":[13],"biopharmaceutical":[14],"industry.":[15],"Transcriptome":[16],"and":[17,75,109,138,258,291,298,343,353,390,477,498,515,589,646,664,694,757,766,776,786,807,821,826,844,863],"proteome":[18],"technologies":[19,74],"have":[20,35,274,427,599,769],"been":[21,275,698],"used":[22,292],"to":[23,37,56,69,76,92,156,163,204,212,218,232,247,293,346,399,414,429,436,457,468,555,616,677,689,711,736,797,874],"probe":[24],"for":[25,277,281,440,564,716,841],"cellular":[26,52,133],"components":[27],"that":[28,40,67,493,641,729],"correlate":[29],"with":[30,310,853],"higher":[31,864],"cell-specific":[32],"productivity,":[33],"but":[34,383],"yet":[36],"yield":[38],"results":[39,330,768],"can":[41,364,760,809],"be":[42,248,421,533,761,790],"translated":[43],"into":[44,633],"practical":[45],"metabolic":[46,119,149,307,359,483,568],"engineering":[47],"strategies.":[48],"The":[49,171,207,424,500,824],"recognition":[50],"complexity":[53],"has":[54,553,697],"led":[55,428,554],"an":[57,447,513,519],"increasing":[58],"adoption":[59],"systems":[61,143],"biology,":[62],"holistic":[64],"investigation":[65,848],"approach":[66,862],"aims":[68],"bring":[70],"together":[71],"different":[72,752],"omics":[73,169],"analyze":[77],"the":[78,89,99,117,123,165,187,214,220,227,252,255,264,282,318,329,348,351,369,384,400,430,454,486,529,549,556,590,619,625,634,639,701,723,744,771,802,854],"resulting":[79],"datasets":[80],"under":[81,638],"unifying":[83],"context.":[84],"Fluxomics":[85],"chosen":[87],"as":[88,234,237],"platform":[90],"context":[91],"investigate":[93],"cell":[94,127,279,301,877],"metabolism":[95,128,221,372],"because":[96,538],"it":[97,411],"captures":[98],"integrated":[100],"effects":[101],"gene":[103],"expression,":[104],"enzyme":[105],"activity,":[106],"metabolite":[107],"availability":[108],"regulation,":[110],"thereby":[111],"providing":[112],"global":[114],"picture":[115],"cell\u2019s":[118],"phenotype.":[120],"At":[121],"present,":[122],"routine":[124],"quantification":[125],"revolves":[129],"around":[130],"very":[131,201,412,609],"basic":[132],"parameters:":[134],"growth,":[135],"substrate":[136,387],"utilization":[137],"product":[139],"formation.":[140],"For":[141],"approach,":[144],"however,":[145],"just":[146],"measuring":[147],"gross":[148],"features":[150,710],"insufficient;":[152],"we":[153,868],"are":[154,489,496,578,643,647,657,708,778,869],"compelled":[155],"perform":[157,437,458,678],"high-resolution,":[158],"large-scale":[159,175,438,572,679,713],"fluxomics":[160,176,840],"in":[161,208,228,323,337,368,394,397,466,485,528,571,829],"order":[162,467],"match":[164],"scale":[166],"other":[168,815],"datasets.":[170],"challenges":[172,425],"performing":[174,837],"come":[177],"from":[178,192,271,377,406,475,624,742],"two":[179,781],"opposing":[180],"fronts.":[181],"Metabolic":[182],"flux":[183,265,360,374,714,879],"analysis":[184,313,361,715],"(MFA)":[185],"estimation":[188],"intracellular":[190],"fluxes":[191,236,322,367],"experimental":[193,240,749,767],"data":[194,303,345,405],"using":[195,239,373,751,784],"stoichiometric":[197],"model,":[198],"process":[200],"much":[202],"susceptible":[203],"modelling":[205,861],"biases.":[206],"silico":[209],"challenge":[210,230],"construct":[213],"most":[215,321],"comprehensive":[216,497],"model":[217,257,288,352,445,637,702],"represent":[219,611],"specific":[224],"cell,":[225],"while":[226,328],"vivo":[229],"resolve":[233,366],"many":[235],"possible":[238],"measurements":[241,735,759],"or":[242,606,704],"constraints.":[243],"A":[244,286,443,461,522,595],"compromise":[245],"needs":[246],"established":[249],"between":[250],"maximizing":[251],"resolution":[253,319,813],"MFA":[256,268,439,537,682],"working":[259,636],"within":[260,834],"technical":[261],"limitations":[262],"experiment.":[266],"Conventional":[267],"models":[269],"assembled":[270],"textbook":[272],"pathways":[273,484,527,569,645,659],"available":[276],"animal":[278,842],"culture":[280,297,302,878],"past":[283],"15":[284,882],"years.":[285],"state-of-the-art":[287],"was":[289,464,675,687,720],"developed":[290,465,676,828],"analyse":[294],"continuous":[295],"hybridoma":[296],"batch":[299],"CHO":[300],"(Chapter":[304,480,574,670,683,763,819],"3).":[305],"Reasonable":[306],"assumptions":[308],"combined":[309],"constraint":[311],"based":[312,581],"exploiting":[314],"irreversibility":[315],"constraints":[316,375],"enabled":[317],"central":[324,370],"carbon":[325,371,550],"metabolism.":[326,851],"However,":[327],"appear":[331],"consistent,":[332],"there":[333,793],"insufficient":[335],"information":[336],"conventional":[338],"measurement":[339],"uptake,":[341],"secretion":[342],"growth":[344],"assess":[347],"completeness":[349],"validity":[354],"all":[356],"assumptions.":[357],"13C":[358,378,403,536,545,681,748],"(13C":[362],"MFA)":[363],"potentially":[365,648],"generated":[376,623],"enrichment":[379,404,546,705],"patterns":[380,547],"metabolites,":[382],"multitude":[385],"uptakes":[388],"(glucose":[389],"amino":[391,408,662,668],"acids)":[392],"seen":[393],"cells,":[396],"addition":[398],"lack":[401],"proteinogenic":[407],"acids,":[409],"makes":[410],"difficult":[413],"anticipate":[415],"how":[416],"labelling":[418],"experiment":[419],"should":[420,789],"carried":[422],"out.":[423],"above":[426],"development":[431,557,724],"systematic":[434,860],"workflow":[435],"cells.":[442,718],"genome-scale":[444],"(GeMs),":[446],"accurate":[448,514],"compilation":[449],"gene-protein-reaction-metabolite":[451],"associations,":[452],"starting":[455],"basis":[456],"whole-cell":[459],"fluxomics.":[460],"semi-automated":[462],"method":[463],"rapidly":[469],"extract":[470],"prototype":[472],"GeM":[474,488,517,531],"KEGG":[476],"UniProtKB":[478],"databases":[479,495],"4).":[481],"Core":[482],"mouse":[487,530,626],"mostly":[490],"complete,":[491],"suggesting":[492],"these":[494,566,655],"sufficient.":[499],"rapid":[501],"prototyping":[502],"system":[503],"takes":[504],"advantage":[505],"this,":[507],"making":[508],"long":[509],"term":[510],"maintenance":[511],"up-to-date":[516],"individual":[520],"possible.":[521],"large":[523],"number":[524],"under-determined":[526,567,621],"cannot":[532],"resolved":[534],"they":[539,642],"do":[540],"not":[541],"produce":[542],"any":[543],"distinctive":[544],"among":[548],"metabolites.":[551],"This":[552,685,719],"SLIPs":[559,577,598,622,630,656],"(short":[560],"linearly":[561],"independent":[562],"pathways)":[563],"visualizing":[565],"contained":[570],"GeMs":[573],"5).":[575],"Certain":[576],"subsequently":[579],"removed":[580],"on":[582,700],"careful":[583],"consideration":[584],"their":[586,593],"pathway":[587],"functions":[588],"implications":[591],"removal.":[594],"majority":[596],"cyclic":[601],"configuration,":[602],"sharing":[603],"similar":[604],"redox":[605],"energy":[607],"co-metabolites;":[608],"few":[610],"true":[612],"conversion":[613],"substrates":[615,756],"products.":[617],"Of":[618],"266":[620],"GeM,":[627],"only":[628],"27":[629],"were":[631],"incorporated":[632],"final":[635],"criterion":[640],"significant":[644],"resolvable":[649],"tracer":[651],"experiments.":[652],"Most":[653],"degradation":[658],"essential":[661],"acids":[663,669],"inter-conversion":[665],"non-essential":[667],"8).":[671,823],"In":[672],"parallel,":[673],"OpenFLUX":[674],"isotopic":[680],"6).":[684],"software":[686],"built":[688],"accept":[690],"multiple":[691],"labelled":[692,816],"substrates,":[693],"no":[695],"restriction":[696,796],"placed":[699],"type":[703],"data.":[706],"These":[707],"necessary":[709],"support":[712],"followed":[721],"design":[727],"strategy":[728],"uses":[730],"analytical":[731],"gradients":[732],"isotopomer":[734,758],"predict":[737],"resolvability":[738],"free":[740],"fluxes,":[741],"which":[743],"effectiveness":[745],"various":[747],"scenarios":[750],"combinations":[753],"input":[755],"evaluated":[762],"7).":[764],"Hypothetical":[765],"confirmed":[770],"predictions":[772],"that,":[773],"when":[774],"glucose":[775,817],"glutamate/glutamine":[777],"simultaneously":[779],"consumed,":[780],"separate":[782],"experiments":[783,880],"[U-13C]-":[785,806],"[1-13C]-glucose,":[787],"respectively,":[788],"performed.":[791],"If":[792],"single":[799],"experiment,":[800],"then":[801],"80:20":[803],"mixture":[804],"[1-13C]-glucose":[808],"provide":[810],"better":[812],"than":[814],"mixtures":[818],"7":[820],"Chapter":[822],"tools":[825],"framework":[827],"this":[830],"thesis":[831],"brings":[832],"us":[833],"reach":[835],"large-scale,":[838],"high-resolution":[839],"hence":[845],"realising":[846],"systems-level":[847],"Moreover,":[852],"establishment":[855],"more":[858],"rigorous,":[859],"functioning":[865],"computational":[866],"tools,":[867],"now":[870],"at":[871],"position":[873],"validate":[875],"performed":[881],"years":[883],"ago.":[884]},"counts_by_year":[],"updated_date":"2026-09-12T09:15:50.089291","created_date":"2016-06-24T00:00:00"}