[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-435603-105":59,"doc-detail-435603-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","biocomputational-frameworks-for-exploring-ornithine-transcarbamylase-mutations-in-otc-deficiency-psychosis-letter-to-the-editor","Biocomputational frameworks for exploring ornithine transcarbamylase mutations in OTC deficiency psychosis - Letter to the Editor","","Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder marked by metabolic derangements and neurocognitive dysfunction, including episodes of acute or chronic psychosis. The letter argues that neuropsychiatric presentations are often misdiagnosed as primary psychotic disorders, delaying appropriate metabolic evaluation and treatment. It highlights how artificial intelligence, molecular dynamics, homology modeling, docking, machine learning, and systems biology may link OTC mutations to psychiatric phenotypes, supporting risk stratification, predictive biomarkers, and precision monitoring.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/biocomputational-frameworks-for-exploring-ornithine-transcarbamylase-mutations-in-otc-deficiency-psychosis-letter-to-the-editor/435603/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/biocomputational-frameworks-for-exploring-ornithine-transcarbamylase-mutations-in-otc-deficiency-psychosis-letter-to-the-editor/435603.png","ImageObject",300,407,{"name":92,"@type":93},"RuangKosong","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes OTCD psychosis challenging to diagnose?","Question",{"text":112,"@type":113},"OTCD neuropsychiatric features, especially episodes of psychosis, remain a mechanistic and diagnostic challenge due to genetic heterogeneity, distinct phenotypic patterns, and incomplete penetrance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How can biocomputational frameworks help in understanding OTC mutations?",{"text":117,"@type":113},"By simulating structural and energetic changes in missense variants, these frameworks can link genotype to clinical presentation and help explain how mutations impair protein stability and enzymatic activity, contributing to ammonia accumulation and downstream neuropsychiatric effects.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are computational predictions not sufficient on their own?",{"text":121,"@type":113},"Computational findings generally need correlation with neurocognitive assessments, biochemical assays, and real-world clinical outcomes, along with careful communication and genetic counseling for asymptomatic carriers.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},435603,1790760556,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},962090883219,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Letter to the Editor  \nBiocomputational frameworks for exploringornithine transcarbamylase mutationsin OTCdeficiency psychosis  \nSarim Hassan Shahab, MBBSa , Fazal Habib, MBBSb ,*  \nTo the Editor,  \nOrnithine transcarbamylase deficiency (OTCD) is anX-linked disorder. It is characterized by hypothermia, hyper -ammonemia, respiratory alkalosis, and late-onset neurocogni -tive dysfunction, including psychosis [1] . Itis the most commonurea cycle disorder throughout the world, occurring 1 in almost8000 newborns worldwide. Traditionally thought of asa metabolic disorder, OTCD’s neuropsychiatric features, inparticular, episodes of acute or chronic psychosis, remaina mechanistic and diagnostic challenge. This is due to thegenetic heterogeneity, different phenotypic patterns, andincomplete penetrance [2,3] . Current development of biocompu -tational frameworks may open up transformative ways for ourunderstanding of how OTC mutations give rise to specificpsychiatric phenotypes.  \nIn a recent study, aritifical intelligence prediction modelsand molecular dynamics simulations have been used to showthat A208T mutations alter substrate affinity, destabilize pro -tein misfolding, and impair enzymatic activity, leading even -tually to ammonia accumulation in OTCD[4] . These advancesoffer a new potential role for biocomputational frameworks.These frameworks can reveal molecular mechanisms linkinggenotype to clinical presentation. Thus, by simulating thestructural and energetic sequences of missense variants, it is  \npossible for researchers to foresee, wellin advance of the clin -ical symptoms, the pathogenicity with striking precision andaccuracy.  \nPsychiatric presentations of OTCD are often misdiagnosed forprimary psychotic disorders; this delays appropriate metabolicevaluation and treatment[2] . Glutamine–glutamine cycling andastrocyte energy metabolism involved in neurotransmission and  \naDepartment of Internal Medicine, Nishtar Medical University, Multan, Pakistan andbDepartment of Internal Medicine, Sher-e-Bangla Medical College, Barisal,Bangladesh  \nSponsorships or competing interests that maybe relevant to content are disclosedatthe end of this article.  \n*Corresponding author. Address: Department of Internal Medicine,Sher-e-Bangla Medical College, Barisal 8200, Bangladesh.  \nE-mail: fazalhabib346@gmail.com (F. Habib).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is anopen access article distributed under the terms of the Creative CommonsAttribution-Non Commercial License 4.0 (CCBY-NC), where itis permissible todownload, share, remix, transform, and buildup the work provided itis properlycited. The work cannot be used commercially without permission from the journal.  \nAnnals of Medicine & Surgery (2026) 88:1011–1012Received 3 November 2025; Accepted 5 November 2025Published online 14 November 2025http://dx.doi.org/10.1097/MS9.0000000000004354  \nneuroplasty become dysregulated in subclinical hyperammone -mia. It results in excitotoxicity and neurotransmitter imbalancethat leads to precipitation of psychotic and manic episodes[5] .Integration of biocomputational methods with neurobiologicaldata allows forthe construction of a mechanistic continuum forneural dysfunction and genetic mutations. For example, by com -bining brain metabolomicand imaging data with molecular simu -lations, we can reveal how specific enzyme defects translate intomitochondrial dynamics and glutamatergic signaling, both ofwhich are critical in psychosis pathophysiology[6] .  \nBy utilizing homology modeling, molecular docking, andmachine learning algorithms, the modern biocomputationalplatform explores the impact of single amino acid substitutionson protein function and structure[7] . Some of the key computa -tional techniques are described in Table 1 .  \nThe extension of such models to OTC variants can thereforeoffer a unique opportunity for risk stratification andthe designof personalized monitoring strategies among carriers.Mo","cbCaimCbcWwG7FSD","https://ap.wps.com/l/cbCaimCbcWwG7FSD","pdf",195115,"English","# Letter to the Editor\n## Background on OTCD and psychosis\n## Biocomputational approaches and mechanistic links\n## Validation, ethics, and translation to precision medicine\n## Conclusion\n## Table 1: Computational techniques for OTC gene mutations","[{\"question\":\"What makes OTCD psychosis challenging to diagnose?\",\"answer\":\"OTCD neuropsychiatric features, especially episodes of psychosis, remain a mechanistic and diagnostic challenge due to genetic heterogeneity, distinct phenotypic patterns, and incomplete penetrance.\"},{\"question\":\"How can biocomputational frameworks help in understanding OTC mutations?\",\"answer\":\"By simulating structural and energetic changes in missense variants, these frameworks can link genotype to clinical presentation and help explain how mutations impair protein stability and enzymatic activity, contributing to ammonia accumulation and downstream neuropsychiatric effects.\"},{\"question\":\"Why are computational predictions not sufficient on their own?\",\"answer\":\"Computational findings generally need correlation with neurocognitive assessments, biochemical assays, and real-world clinical outcomes, along with careful communication and genetic counseling for asymptomatic carriers.\"}]","Biocomputational frameworks for exploring ornithine transcarbamylase mutations in OTC deficiency psychosis - Letter to the Editor | PDF",1790674376]