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We developed Constraint-based Optimization of Metabolic Objectives (COMO), a user-friendly pipeline that integrates multi-omics data processing, context-specific metabolic model development, simulations, drug databases and disease data to aid drug discovery. COMO can be installed as a Docker Image or with Conda and includes intuitive instructions within a Jupyter Lab environment. It provides a comprehensive solution for the integration of bulk and single-cell RNA-seq, microarrays and proteomics outputs to develop context-specific metabolic models. Using public databases, open-source solutions for model construction and a streamlined approach for predicting repurposable drugs, COMO enables researchers to investigate low-cost alternatives and novel disease treatments. As a case study, we used the pipeline to construct metabolic models of B cells, which simulate and analyze them to predict metabolic drug targets for rheumatoid arthritis and systemic lupus erythematosus, respectively. COMO can be used to construct models for any cell or tissue type and identify drugs for any human disease where metabolic inhibition is relevant. The pipeline has the potential to improve the health of the global community cost-effectively by providing high-confidence targets to pursue in preclinical and clinical studies. The source code of the COMO pipeline is available at https:\/\/github.com\/HelikarLab\/COMO. The Docker image can be pulled at https:\/\/github.com\/HelikarLab\/COMO\/pkgs\/container\/como.<\/jats:p>","DOI":"10.1093\/bib\/bbad387","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T02:15:09Z","timestamp":1699323309000},"source":"Crossref","is-referenced-by-count":10,"title":["COMO: a pipeline for multi-omics data integration in metabolic modeling and drug discovery"],"prefix":"10.1093","volume":"24","author":[{"given":"Brandt","family":"Bessell","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln , NE ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josh","family":"Loecker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Nebraska-Lincoln , NE ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of 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