{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:29:43Z","timestamp":1768004983638,"version":"3.49.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Minister of Economy and Competitiveness of Spain","award":["PID2019-110344RB-I00"],"award-info":[{"award-number":["PID2019-110344RB-I00"]}]},{"name":"Minister of Economy and Competitiveness of Spain","award":["PID2022-143298OB-I00"],"award-info":[{"award-number":["PID2022-143298OB-I00"]}]},{"name":"PIBA Programme of the Basque Government","award":["PIBA_2020_01_0055"],"award-info":[{"award-number":["PIBA_2020_01_0055"]}]},{"name":"ERANET program ERAPerMed"},{"name":"Elkartek programme of the Basque Government","award":["KK-2022\/00045"],"award-info":[{"award-number":["KK-2022\/00045"]}]},{"name":"Basque Government predoctoral","award":["PRE_2021_2_0025"],"award-info":[{"award-number":["PRE_2021_2_0025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cancer metabolism is a marvellously complex topic, in part, due to the reprogramming of its pathways to self-sustain the malignant phenotype in the disease, to the detriment of its healthy counterpart. Understanding these adjustments can provide novel targeted therapies that could disrupt and impair proliferation of cancerous cells. For this very purpose, genome-scale metabolic models (GEMs) have been developed, with Human1 being the most recent reconstruction of the human metabolism. Based on GEMs, we introduced the genetic Minimal Cut Set (gMCS) approach, an uncontextualized methodology that exploits the concepts of synthetic lethality to predict metabolic vulnerabilities in cancer. gMCSs define a set of genes whose knockout would render the cell unviable by disrupting an essential metabolic task in GEMs, thus, making cellular proliferation impossible. Here, we summarize the gMCS approach and review the current state of the methodology by performing a systematic meta-analysis based on two datasets of gene essentiality in cancer. First, we assess several thresholds and distinct methodologies for discerning highly and lowly expressed genes. Then, we address the premise that gMCSs of distinct length should have the same predictive power. Finally, we question the importance of a gene partaking in multiple gMCSs and analyze the importance of all the essential metabolic tasks defined in Human1. Our meta-analysis resulted in parameter evaluation to increase the predictive power for the gMCS approach, as well as a significant reduction of computation times by only selecting the crucial gMCS lengths, proposing the pertinency of particular parameters for the peak processing of gMCS.<\/jats:p>","DOI":"10.1093\/bib\/bbae115","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T13:00:23Z","timestamp":1711630823000},"source":"Crossref","is-referenced-by-count":5,"title":["Review and meta-analysis of the genetic Minimal Cut Set approach for gene essentiality prediction in cancer metabolism"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-6616","authenticated-orcid":false,"given":"Danel","family":"Olaverri-Mendizabal","sequence":"first","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , Manuel de Lardiz\u00e1bal 13, San Sebasti\u00e1n 20018 , Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3769-5419","authenticated-orcid":false,"given":"Luis V","family":"Valc\u00e1rcel","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , Manuel de Lardiz\u00e1bal 13, San Sebasti\u00e1n 20018 , Spain"},{"name":"Biomedical Engineering Center, University of Navarra , Campus Universitario, Pamplona, Navarra 31009 , Spain"},{"name":"Instituto de Ciencia de los Datos e Inteligencia Artificial (DATAI), University of Navarra , Campus Universitario, Pamplona 31080 , Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4324-3371","authenticated-orcid":false,"given":"Naroa","family":"Barrena","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , Manuel de Lardiz\u00e1bal 13, San Sebasti\u00e1n 20018 , Spain"}]},{"given":"Carlos J","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , Manuel de Lardiz\u00e1bal 13, San Sebasti\u00e1n 20018 , Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-3105","authenticated-orcid":false,"given":"Francisco J","family":"Planes","sequence":"additional","affiliation":[{"name":"Tecnun School of Engineering, University of Navarra , Manuel de Lardiz\u00e1bal 13, San Sebasti\u00e1n 20018 , Spain"},{"name":"Biomedical Engineering Center, University of Navarra , Campus Universitario, Pamplona, Navarra 31009 , Spain"},{"name":"Instituto de Ciencia de los Datos e Inteligencia Artificial (DATAI), University of Navarra , Campus Universitario, Pamplona 31080 , Spain"}]}],"member":"286","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"2024041712531181400_ref1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrg.2017.47","article-title":"Synthetic lethality and cancer","volume":"18","author":"O\u2019Neil","year":"2017","journal-title":"Nat Rev Genet"},{"key":"2024041712531181400_ref2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s41467-021-21478-9","article-title":"Combinatorial CRISPR screen identifies fitness effects of gene paralogues","volume":"12","author":"Thompson","year":"2021","journal-title":"Nat Commun"},{"key":"2024041712531181400_ref3","doi-asserted-by":"crossref","first-page":"e1008466","DOI":"10.1371\/journal.pgen.1008466","article-title":"Paralog buffering contributes to the variable essentiality of genes in cancer cell lines","volume":"15","author":"Kegel","year":"2019","journal-title":"PLoS Genet"},{"key":"2024041712531181400_ref4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1093\/bioinformatics\/btab709","article-title":"Rediscover: an R package to identify mutually exclusive mutations","volume":"38","author":"Ferrer-Bonsoms","year":"2022","journal-title":"Bioinformatics"},{"key":"2024041712531181400_ref5","first-page":"1","article-title":"Computational methods, databases and tools for synthetic lethality prediction","volume":"23","author":"Wang","year":"2022","journal-title":"Brief Bioinform"},{"key":"2024041712531181400_ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/msb.2011.51","article-title":"Predicting selective drug targets in cancer through metabolic networks","volume":"7","author":"Folger","year":"2011","journal-title":"Mol Syst Biol"},{"key":"2024041712531181400_ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/msb.145122","article-title":"Identification of anticancer drugs for hepatocellular carcinoma through personalized genome-scale metabolic modeling","volume":"10","author":"Agren","year":"2014","journal-title":"Mol Syst Biol"},{"key":"2024041712531181400_ref8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ebiom.2019.04.046","article-title":"Identifying and targeting cancer-specific metabolism with network-based drug target prediction","volume":"43","author":"Pacheco","year":"2019","journal-title":"EBioMedicine"},{"key":"2024041712531181400_ref9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scisignal.aaz1482","article-title":"An atlas of human metabolism","volume":"13","author":"Robinson","year":"2020","journal-title":"Sci Signal"},{"key":"2024041712531181400_ref10","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41419-023-05955-1","article-title":"Metabolic modelling-based in silico drug target prediction identifies six novel repurposable drugs for melanoma","volume":"14","author":"Bintener","year":"2023","journal-title":"Cell Death Dis"},{"key":"2024041712531181400_ref11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-00555-y","article-title":"An in-silico approach to predict and exploit synthetic lethality in cancer metabolism","volume":"8","author":"Apaolaza","year":"2017","journal-title":"Nat Commun"},{"key":"2024041712531181400_ref12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/bioinformatics\/bty656","article-title":"GMCS: fast computation of genetic minimal cut sets in large networks","volume":"35","author":"Apaolaza","year":"2019","journal-title":"Bioinformatics"},{"key":"2024041712531181400_ref13","first-page":"1","article-title":"gMCStool: automated network-based tool to search for metabolic","author":"Valc\u00e1rcel","year":"2022"},{"key":"2024041712531181400_ref14","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1038\/s41375-022-01601-5","article-title":"The bone marrow niche regulates redox and energy balance in MLL::AF9 leukemia stem cells","volume":"36","author":"Vi\u00f1ado","year":"2022","journal-title":"Leukemia"},{"key":"2024041712531181400_ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pcbi.1009395","article-title":"A network-based approach to integrate nutrient microenvironment in the prediction of synthetic lethality in cancer metabolism","volume":"18","author":"Apaolaza","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2024041712531181400_ref16","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"2024041712531181400_ref17","doi-asserted-by":"crossref","DOI":"10.1038\/s41540-023-00296-3","article-title":"Synthetic lethality in large-scale integrated metabolic and regulatory network models of human cells","author":"Barrena","year":"2023"},{"key":"2024041712531181400_ref18","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41596-018-0098-2","article-title":"Creation and analysis of biochemical constraint-based models using the COBRA toolbox v.3.0","volume":"14","author":"Heirendt","year":"2019","journal-title":"Nat Protoc"},{"key":"2024041712531181400_ref19","article-title":"gMCSpy: efficient and accurate computation of genetic minimal cut sets in python supplementary information","author":"Rodriguez","year":"2024"},{"key":"2024041712531181400_ref20","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/j.cell.2015.11.015","article-title":"High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities","volume":"163","author":"Hart","year":"2015","journal-title":"Cell"},{"key":"2024041712531181400_ref21","author":"DepMap, Broad","year":"2021"},{"key":"2024041712531181400_ref22","doi-asserted-by":"crossref","first-page":"e1007185","DOI":"10.1371\/journal.pcbi.1007185","article-title":"Assessing key decisions for transcriptomic data integration in biochemical networks","volume":"15","author":"Richelle","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"2024041712531181400_ref23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2024041712531181400_ref24","doi-asserted-by":"crossref","first-page":"D387","DOI":"10.1093\/nar\/gkab1053","article-title":"The sequence read archive: a decade more of explosive growth","volume":"50","author":"Katz","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2024041712531181400_ref25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-generation characterization of the cancer cell line Encyclopedia","volume":"569","author":"Ghandi","year":"2019","journal-title":"Nature"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/3\/bbae115\/57242337\/bbae115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/3\/bbae115\/57242337\/bbae115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T19:08:18Z","timestamp":1713380898000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae115\/7636145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,27]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,27]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae115","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,3,27]]},"article-number":"bbae115"}}