{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:23:37Z","timestamp":1773275017716,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012109","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000}}],"reference-count":309,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007911","name":"University of California, San Diego","doi-asserted-by":"publisher","award":["The Y.C. Fung Chair in Bioengineering"],"award-info":[{"award-number":["The Y.C. Fung Chair in Bioengineering"]}],"id":[{"id":"10.13039\/100007911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL146442, R01HL149714, and R01HL148151"],"award-info":[{"award-number":["R01HL146442, R01HL149714, and R01HL148151"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Advancements with cost-effective, high-throughput omics technologies have had a transformative effect on both fundamental and translational research in the medical sciences. These advancements have facilitated a departure from the traditional view of human red blood cells (RBCs) as mere carriers of hemoglobin, devoid of significant biological complexity. Over the past decade, proteomic analyses have identified a growing number of different proteins present within RBCs, enabling systems biology analysis of their physiological functions. Here, we introduce RBC-GEM, one of the most comprehensive, curated genome-scale metabolic reconstructions of a specific human cell type to-date. It was developed through meta-analysis of proteomic data from 29 studies published over the past two decades resulting in an RBC proteome composed of more than 4,600 distinct proteins. Through workflow-guided manual curation, we have compiled the metabolic reactions carried out by this proteome to form a genome-scale metabolic model (GEM) of the RBC. RBC-GEM is hosted on a version-controlled GitHub repository, ensuring adherence to the standardized protocols for metabolic reconstruction quality control and data stewardship principles. RBC-GEM represents a metabolic network is a consisting of 820 genes encoding proteins acting on 1,685 unique metabolites through 2,723 biochemical reactions: a 740% size expansion over its predecessor. We demonstrated the utility of RBC-GEM by creating context-specific proteome-constrained models derived from proteomic data of stored RBCs for 616 blood donors, and classified reactions based on their simulated abundance dependence. This reconstruction as an up-to-date curated GEM can be used for contextualization of data and for the construction of a computational whole-cell models of the human RBC.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012109","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T17:26:12Z","timestamp":1741800372000},"page":"e1012109","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["RBC-GEM: A genome-scale metabolic model for systems biology of the human red blood cell"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-5050","authenticated-orcid":true,"given":"Zachary 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