Applying data science methodologies with artificial intelligence variant reinterpretation to map and estimate genetic disorder prevalence utilizing clinical data.

Data science methodologies can be utilized to ascertain and analyze clinical genetic data that is often unstructured and rarely used outside of patient encounters. Genetic variants from all genetic testing resulting to a large pediatric healthcare system for a 5-year period were obtained and reinterpreted utilizing the previously validated Franklin© Artificial Intelligence (AI). Using PowerBI©, the data were further matched to patients in the electronic healthcare record to associate with demographic data to generate a variant data table and mapped by ZIP codes. Three thousand and sixty-five variants were identified and 98% were matched to patients with geographic data. Franklin© changed the interpretation for 24% of variants. One hundred and fifty-six clinically actionable variant reinterpretations were made. A total of 739 Mendelian genetic disorders were identified with disorder prevalence estimation. Mapping of variants demonstrated hot-spots for pathogenic genetic variation such as PEX6-associated Zellweger Spectrum Disorder. Seven patients were identified with Bardet-Biedl syndrome and seven patients with Rett syndrome amenable to newly FDA-approved therapeutics. Utilizing readily available software we developed a database and Exploratory Data Analysis (EDA) methodology enabling us to systematically reinterpret variants, estimate variant prevalence, identify conditions amenable to new treatments, and localize geographies enriched for pathogenic variants.

Effects of Oxytocin Administration on Cue-Induced Craving in Co-occurring Alcohol Use Disorder and PTSD: A Within-Participant Randomized Clinical Trial.

BACKGROUND: Individuals with alcohol use disorder (AUD) are much more likely to meet criteria for posttraumatic stress disorder (PTSD) than the general population. Compared to AUD alone, those with comorbid AUD-PTSD experience worse outcomes. Prior literature suggests that oxytocin, a hypothalamic neuropeptide, may be effective in the treatment of both AUD and PTSD when administered intranasally, although specific mechanisms remain elusive. METHODS: Forty-seven male patients with comorbid AUD-PTSD were administered intranasal oxytocin in a randomized, double-blind, dose-ranging (20 IU, 40 IU, and matched placebo), within-participant design with study visits at least 1 week apart. A cue-induced craving paradigm was conducted using each participant's preferred alcoholic beverage versus a neutral water cue. Self-reported alcohol craving and heart rate (HR) were recorded and analyzed using linear mixed-effect models. RESULTS: While alcohol cues significantly induced self-reported craving and increased HR compared to neutral water cues, neither dosage of oxytocin compared to placebo reduced self-reported cue-induced alcohol craving nor cue-induced changes in HR in patients with PTSD-AUD. CONCLUSIONS: These preliminary findings suggest that oxytocin does not affect cue-induced craving. Our results contribute to an ever-growing field of research investigating the effects of intranasal oxytocin on the symptoms of substance use disorders and will help further refine methodology and streamline future inquiries in this area.