{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T05:14:03Z","timestamp":1783228443008,"version":"3.54.6"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL151392"],"award-info":[{"award-number":["R01HL151392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Current strategies for optimizing gene therapeutics and recombinant protein production typically rely on universal host codon usage indices. However, there is a growing shift toward incorporating gene-specific traits to enhance therapeutic characteristics. In this study, we investigate position-specific variations in codon and adjacent codon-pair usage biases (CPUBs), offering potential for more tailored gene engineering approaches. We focus our analysis on the coding sequences of four coagulation factors: ADAMTS13, von Willebrand factor, factor VIII, and factor IX, which have been used in therapeutic applications. By aligning transcript homologs with human sequences for each gene using Discontiguous Megablast and MACSE, we assess \u201csequence-position-specific\u201d codon and CPUBs; 157 homologous sequences for ADAMTS13, 148 for F8, 96 for F9, and 202 for VWF. Species with homologs ranged from Primates and Artiodactyla (Even-toed Ungulates) to Testudines. Statistically significant, position-specific positive CPUBs were observed that contrasted with conventional, alignment-specific negative CPUBs. Moreover, we observed that codon and codon-pair usages are highly associated at sequence positions despite little or no association in conventional-position-agnostic analyses. The distinct biases observed at different positions\/functionally critical domains in coding sequences highlight the importance of considering position-specific effects in codon optimization strategies.<\/jats:p>","DOI":"10.1093\/nargab\/lqaf169","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:08:54Z","timestamp":1761743334000},"source":"Crossref","is-referenced-by-count":1,"title":["Uncovering position-specific patterns in codon and codon-pair usage in candidate genes associated with blood coagulation diseases"],"prefix":"10.1093","volume":"7","author":[{"given":"Nathan J","family":"Clement","sequence":"first","affiliation":[{"name":"Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD 20993 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuko","family":"Hamasaki-Katagiri","sequence":"additional","affiliation":[{"name":"Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD 20993 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lin","sequence":"additional","affiliation":[{"name":"Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD 20993 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton A","family":"Komar","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University , Cleveland, OH 44115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"DiCuccio","sequence":"additional","affiliation":[{"name":"Rockville , MD 20853 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haim","family":"Bar","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Connecticut , Storrs, CT 06269 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8585","authenticated-orcid":false,"given":"Chava","family":"Kimchi-Sarfaty","sequence":"additional","affiliation":[{"name":"Hemostasis Branch 1, Division of Hemostasis, Office of Plasma Protein Therapeutics, Office Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD 20993 ,","place":["United 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