Detection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSMC enables biobank-scale detection and dating of IBD segments within several thousands of years in the past. We apply FastSMC to 487,409 UK Biobank samples and detect ~214 billion IBD segments transmitted by shared ancestors within the past 1500 years, obtaining a fine-grained picture of genetic relatedness in the UK. Sharing of common ancestors strongly correlates with geographic distance, enabling the use of genomic data to localize a sample’s birth coordinates with a median error of 45 km. We seek evidence of recent positive selection by identifying loci with unusually strong shared ancestry and detect 12 genome-wide significant signals. We devise an IBD-based test for association between phenotype and ultra-rare loss-of-function variation, identifying 29 association signals in 7 blood-related traits.
The wide application of next-generation sequencing (NGS), mainly through whole genome, exome and transcriptome sequencing, provides a high-resolution and global view of the cancer genome. Coupled with powerful bioinformatics tools, NGS promises to revolutionize cancer research, diagnosis and therapy. In this paper, we review the recent advances in NGS-based cancer genomic research as well as clinical application, summarize the current integrative oncogenomic projects, resources and computational algorithms, and discuss the challenge and future directions in the research and clinical application of cancer genomic sequencing.
SARS-CoV-2 vaccines are powerful tools to combat the COVID-19 pandemic, but vaccine hesitancy threatens these vaccines' effectiveness. To address COVID-19 vaccine hesitancy and ensure equitable distribution, understanding the extent of and factors associated with vaccine hesitancy is critical. We report the results of a large nationwide study conducted December 2020-January 2021 of 34,470 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. Nineteen percent of respondents expressed vaccine hesitancy, the majority being undecided. Vaccine hesitancy was significant among females, younger people, minority and low-income communities, healthcare and essential workers, rural residents, geographical regions with higher COVID-19 burden, those who did not use protective measures, and those who did not receive COVID-19 tests. Our findings support the need for targeted efforts to develop education and outreach programs to overcome vaccine hesitancy and improve equitable access, diversity, and inclusion in the national response to COVID-19.
The wide application of next-generation sequencing (NGS), mainly through whole genome, exome and transcriptome sequencing, provides a high-resolution and global view of the cancer genome. Coupled with powerful bioinformatics tools, NGS promises to revolutionize cancer research, diagnosis and therapy. In this paper, we review the recent advances in NGS-based cancer genomic research as well as clinical application, summarize the current integrative oncogenomic projects, resources and computational algorithms, and discuss the challenge and future directions in the research and clinical application of cancer genomic sequencing.
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