Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

Standardization, Collaboration, and Education in the Implementation of Artificial Intelligence in Otolaryngology: The Key to Scalable Impact.

The study delves into the crucial role of standardization, collaboration, and education in the integration of artificial intelligence (AI) in otolaryngology. It emphasizes the necessity of large, diverse datasets for effective AI implementation in health care, particularly in otolaryngology, due to its reliance on medical imagery and diverse instruments. The text identifies current barriers, including siloed work in academia and sparse academic-industrial partnerships, while proposing solutions like forming interdisciplinary teams and aligning incentives. Moreover, it discusses the importance of standardizing AI projects through system reporting and advocates for AI education and literacy among otolaryngology practitioners.

Voice as a Biomarker in Health-Tech: Mapping the Evolving Landscape of Voice Biomarkers in the Start-Up World.

OBJECTIVE: The vocal biomarkers market was worth $1.9B in 2021 and is projected to exceed $5.1B by 2028, for a compound annual growth rate of 15.15%. The investment growth demonstrates a blossoming interest in voice and artificial intelligence (AI) as it relates to human health. The objective of this study was to map the current landscape of start-ups utilizing voice as a biomarker in health-tech. DATA SOURCES: A comprehensive search for start-ups was conducted using Google, LinkedIn, Twitter, and Facebook. A review of the research was performed using company website, PubMed, and Google Scholar. REVIEW METHODS: A 3-pronged approach was taken to thoroughly map the landscape. First, an internet search was conducted to identify current start-ups focusing on products relating to voice as a biomarker of health. Second, Crunchbase was utilized to collect financial and organizational information. Third, a review of the literature was conducted to analyze publications associated with the identified start-ups. RESULTS: A total of 27 start-up start-ups with a focus in the utilization of AI for developing biomarkers of health from the human voice were identified. Twenty-four of these start-ups garnered $178,808,039 in investments. The 27 start-ups published 194 publications combined, 128 (66%) of which were peer reviewed. CONCLUSION: There is growing enthusiasm surrounding voice as a biomarker in health-tech. Academic drive may complement commercialization to best achieve progress in this arena. More research is needed to accurately capture the entirety of the field, including larger industry players, academic institutions, and non-English content.