Optimizing HaploSeq for whole-genome phased haplotypes in biomedical applications

DESCRIPTION provided by applicant Phenomenal advances in DNA sequencing technologies have enabled systematic identification of genetic variants in human individuals and the recent FDA marketing authorization of the first next generation genome sequencer signals the arrival of a new era of pharmacogenomics and personalized medicine Nevertheless DNA sequencing alone fails to provide complete information on the genetic makeup of an individual as two homologous sets of chromosomes are present in the human genome Delineation of both maternal and paternal copies or haplotypes is critical for determining an individualandapos s genetic composition and for understanding the structure and function of the human genome and its role in health and disease Yet genome scale haplotyping or andquot phasingandquot of DNA variants has long remained an elusive goal Existing approaches are prohibitively expensive technically challenging require specialized instrumentation or fall far short of reconstructing chromosome spanning haplotypes Arima Genomics has recently developed an innovative new approach for whole genome haplotyping combining proximity ligation and DNA sequencing with a probabilistic algorithm for haplotype assembly This new method known as HaploSeq achieves chromosome spanning haplotypes with high completeness resolution and accuracy in mammalian genomes As a cost effective streamlined technology HaploSeq is poised to underpin a new standard in genome sequencing in biomedical applications and other markets from pharmacogenomics to agricultural biotechnology The objectives of Arima Genomicsandapos proposed Randamp D efforts involve improvement of HaploSeqandapos s ability to phase rare variants in human cells by adapting the protocol to achieve more uniform genome coverage extension of the HaploSeq algorithmandapos s capabilities to provide genotypes concurrently with haplotypes from the same source sequencing data by developing a new andquot smart mappingandquot computational module and demonstration and benchmarking of HaploSeqandapos s utility in ongoing next generation genetic association studies in partnership with clinical research collaborators at UC San Diego Successful completion of our research aims will contribute invaluable new knowledge to ongoing investigations of how human genetic variation influences the gene regulatory networks involved in cardiac biology and disease and will substantially advance the capabilities of HaploSeq toward commercial viability in diverse research biomedical and clinical sequencing applications HaploSeq promises to greatly enhance our understanding of human genetics in health and contribute to the realization of personalized medicine PUBLIC HEALTH RELEVANCE Delineating both maternal and paternal genetic copies or haplotypes is critical for determining an individualandapos s genetic composition and for understanding the structure and function of the human genome and its role in health and disease yet genome scale haplotyping or andquot phasingandquot of DNA variants has long remained an elusive goal Arima Genomics has recently developed an innovative cost effective and streamlined technology for whole genome haplotyping in humans known as HaploSeq This new method will have broad impacts in diverse research biomedical and clinical sequencing applications and promises to improve our understanding of human genetics in health and contribute to the realization of personalized medicine