possible by HudsonAlpha in collaboration with Discovery Life Sciences (DLS) , a company located on the Hudson- Alpha campus. HudsonAlpha Discovery, a division of DLS, began performing long-read sequencing work with the All of Us program in 2019. An initial pilot study identified PacBio ® circular consensus sequencing (also called “Hi-fi” sequencing) as the most appropriate platform for the All of Us program data. HudsonAlpha is on track to complete a long-read genome for more than 2,000 All of Us participants. This is one of the first and largest long-read sequencing proj- ects of its kind. The information gained from such a large cohort is invaluable to the All of Us program and the ge- nomics community as a whole. HudsonAlpha delivers the sequencing data to the bioinformatics team at The Broad Institute for analysis, alignment, and eventually release into the All of Us Researcher Workbench. The first release will be made available in the winter of 2022.
of researchers, including several members of the HGSC, set out to sequence the Ceratopteris richardii fern genome, which has one of the highest chromosome counts of any plant. With the high-quality genome sequence in hand, the research team was surprised to find that the genome was so large because Ceratopteris accumulated millions of jumping genes, likely inherited from other organisms. Many of the jumping genes in Ceratopteris code for defense-related products, although how the fern uses most of them requires further studies. The information gleaned from the complex genome could have downstream practical applications ranging from developing novel biopesticides to innovative new conservation strategies. DETECTION OF STRUCTURAL VARIANTS IN HUMANS Several HudsonAlpha labs, including Faculty Investigator Greg Cooper, PhD , are using long-read sequencing technology to help physicians make diagnoses for pediatric patients affected by undiagnosed neurodevelop- mental disorders. The HGSC team used long-read sequencing to re- analyze the genomes of six family trios (mom, dad, and the affected child) that each had children affected by neurode- velopmental disorders 2 . The families previously had their genomes sequenced with short-read technology, but no causal genetic variant was identified. Cooper and his team found thousands of genetic variants in each family that were previously undetectable using short-read technology. Among them, the team identified likely pathogenic vari- ation in two of the six children. Reanalysis of short-read genomes is an ongoing part of the lab’s work. ALL OF US LONG-READ SEQUENCING DATASET The National Institute of Health’s All of Us program is committed to using the most cutting-edge techniques to collect and analyze health information from over one mil- lion diverse Americans. One example of this is using long- read sequencing technology to sequence DNA samples. The first set of All of Us long-read sequencing data is made
CONSORTIUM FOR LONG READ SEQUENCING (COLORS)
Because of their position as leaders in the long-read sequencing field, several HudsonAlpha researchers were invited to participate in a new initiative aiming to accelerate the utility of long-read human genome data- sets. The Consortium for Long Read Sequencing (CoLoRS) was created by PacBio ® , a leading developer of high- quality, highly accurate sequencing solutions. Cooper, Grimwood, and Schmutz are among the founding members of the consortium. Long-read sequencing covers regions of the genome inaccessible to other technologies, providing unique insights for disease and genome research. CoLoRS is focused on cataloging and providing frequency information for all classes of variation found within the human genome using long-read whole genome sequencing. The first set of genomic data to populate the CoLoRS database will be extracted from pre-existing and ongoing research projects conducted by consortium members. HudsonAlpha has already submitted 80 samples to the database, with more on the way, which will go live in late 2022. ■
RESEARCH REPORT
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