{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:14:35Z","timestamp":1772172875657,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009157","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-IDEX-0003-02"],"award-info":[{"award-number":["ANR-11-IDEX-0003-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species,\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    and\n                    <jats:italic>S. uvarum<\/jats:italic>\n                    . The data included protein abundances, integrated traits (life-history\/fermentation) and computational estimates of metabolic fluxes. Results highlighted that the negative correlation between production traits such as population carrying capacity (\n                    <jats:italic>K<\/jats:italic>\n                    ) and traits associated with growth and fermentation rates (\n                    <jats:italic>J<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) is explained by a differential usage of energy production pathways: a high\n                    <jats:italic>K<\/jats:italic>\n                    was associated with high TCA fluxes, while a high\n                    <jats:italic>J<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results.\n                  <\/jats:p>\n                  <jats:p>This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009157","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T13:46:42Z","timestamp":1626356802000},"page":"e1009157","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Data integration uncovers the metabolic bases of phenotypic variation in yeast"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-428X","authenticated-orcid":true,"given":"Marianyela Sabina","family":"Petrizzelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3395-7901","authenticated-orcid":true,"given":"Dominique","family":"de Vienne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3032-9838","authenticated-orcid":true,"given":"Thibault","family":"Nidelet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"No\u00fbs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-341X","authenticated-orcid":true,"given":"Christine","family":"Dillmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"pcbi.1009157.ref001","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.27468","volume-title":"The Genetical Theory of Natural Selection","author":"RA Fisher","year":"1930"},{"key":"pcbi.1009157.ref002","volume-title":"The evolution of life histories","author":"S Stearns","year":"1992"},{"issue":"3","key":"pcbi.1009157.ref003","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrg2949","article-title":"The pleiotropic structure of the genotype-phenotype map: the evolvability of complex organisms","volume":"12","author":"GP Wagner","year":"2011","journal-title":"Nat Rev Genet"},{"issue":"3","key":"pcbi.1009157.ref004","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10295-015-1585-x","article-title":"Methods and advances in metabolic flux analysis: a mini-review","volume":"42","author":"MR Antoniewicz","year":"2015","journal-title":"J Ind Microbiol Biotechnol"},{"issue":"7216","key":"pcbi.1009157.ref005","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/4551054a","article-title":"Systems biology: Metabonomics","volume":"455","author":"JK Nicholson","year":"2008","journal-title":"Nature"},{"key":"pcbi.1009157.ref006","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.12688\/f1000research.11495.1","article-title":"New frontiers in metabolomics: from measurement to insight","volume":"6","author":"E Riekeberg","year":"2017","journal-title":"F1000Research"},{"issue":"3","key":"pcbi.1009157.ref007","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1042\/bj2380781","article-title":"Fat synthesis in adipose tissue. 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