In VAs Million Veteran Program, researchers are mapping the human genome by using genotypinga process that spells out several hundred thousand data points, one-by-one. (Photo for illustrative purposes only Getty Images/alanphillips)
May 19, 2022
By Mike Richman VA Research Communications
"The importance of this cannot be overstated. Using TOPMed's imputation panel vastly enriches MVP's genetic database."
Since 2011, more than 875,000 Veterans have donated their DNA to the VA Million Veteran Program (MVP). In the program, VA researchers are sequencing Veterans' genomesa complete set of genetic materialto better understand how genes, lifestyles, and military exposures can affect a persons health and risk for illness.
Centrifugation helps scientists extract DNA from a Veteran's blood sample and prepare the DNA for genetic analysis, either through genotyping or whole genome sequencing.
Centrifugation helps scientists extract DNA from a Veteran's blood sample and prepare the DNA for genetic analysis, either through genotyping or whole genome sequencing.
Researchers map the genomes using genotypinga process that spells out several hundred thousand data points, one-by-one. To fill in any missing data, scientists look to genomes where all data points have been fully sequenced. These genomes are used as a reference to determine the missing letters.
MVP has created whole genome sequences for over 140,000 Veterans. However, it takes time to process this large amount of data and make it available for research. It takes even more time to develop a calculation toolcalled an imputation panelto determine the missing data points that remain when genotyping is complete.
In efforts to find a more accurate and cost-effective method for predicting missing genomic data points, VA investigators found a potential interim solution just across town in Bethesda, Maryland: a genomic research program at the National Institutes of Health (NIH).
As part of that solution, MVP has been collaborating with NIH to use a reference panel for imputation.
The panel is run by TOPMedthe Trans-Omics for Precision Medicine Program. The program, funded by NIHs National Heart, Lung, and Blood Institute (NHLBI), aims to generate scientific resources that will improve the understanding of heart, lung, blood, and sleep disorders and advance precision medicine, an approach in health care that takes into account a persons gene variants and his or her environment and lifestyle to find the right treatment.
Since 2014, TOPMed has collected the entire genome sequence of more than 100,000 people. Scientists created a new reference genome and imputation panel based off these whole-genome sequences.
This first-of-its kind imputation panel offers far more statistical accuracy than any previous imputation panels. In that way, it will help scientists develop better treatments specific to a persons genes and environment.
MVP wanted to find a way to use this tool to improve its genetic database, now one of the largest in the world. The database supports the work of more than 500 researchers across VA. With better genetic data, the researchers can uncover new genetic markers associated with disease in Veterans that could someday revolutionize their health care. As such, MVP leaders set out to strike up a partnership with their colleagues in Bethesda.
In 2018, TOPMed and VA began discussions with the goal of using this new imputation panel to re-do genetic analysis on DNA shared by hundreds of thousands of Veterans in MVP.
The importance of this cannot be overstated, says Dr. Phil Tsao, MVPs co-principal investigator in data generation and access. Using TOPMeds imputation panel vastly enriches MVPs genetic database. Over 500 researchers use MVP data to find new genetic markers related to health and illness in Veterans. With better data, they can make better findings. With better findings, we can offer Veterans better care with more laser-focused accuracy.
The TOPMed reference genome for this imputation panel was selected with racial and ethnic diversity in mind. This means VA can make much more accurate sequencing predictions for people who come from non-European ancestry. This is critical for MVP, since approximately 30% of the more than 875,000 Veterans in MVP are from non-European descent.
To be able to more accurately assemble their genome means the research we do on non-European Veteran populations will be much more thorough, says Dr. Sumitra Muralidhar, the director of MVP. That means we can discover new, never-before-known genetic markers connected with health and disease in Veteran populations of non-European descent.
In 2020, VA acquired the TOPMed imputation panel from NIH, and researchers began methodically re-analyzing and updating more than 650,000 genomes from Veterans who provided blood samples when they joined MVP. In December 2021, the update was complete and the new, upgraded data on hundreds of thousands of Veterans became available to research.
Due to our collaboration with TOPMed, we have better genetic data now, which will hopefully lead to findings of new genetic markers for diseases, specifically in diverse Veterans, Muralidhar says. The end result will hopefully be new discoveries and better treatments, as well as a better understanding of the biology of diseases. That way, we can offer more precise treatments for diseases and other health conditions.
Now that MVPs genetic data is updated with TOPMeds reference panel, any findings from MVP data can becompared and validated with findings from other research based on genomes that were also imputed using TOPMeds reference panel.
Use of the TOPMed reference panel in MVP, which is one of the worlds largest genomic biobanks, allows for more collaboration between NIH and VA scientists to cross-validate each others analysis results, says Dr. Saiju Pyarajan, director of the Center for Data and Computational Sciences at the VA Boston Healthcare System. The more people around the world who have been compared to the same reference sample, the more were able to drastically increase the confidence in the conclusions or results from these genomic analyses. This is wonderful for the future of precision medicine.
VA Research Currents archives || Sign up for VA Research updates
Continue reading here:
Mapping out the human genome - VA's Office of Research and Development
- The complete plastome sequences of invasive weed Parthenium hysterophorus: genome organization, evolutionary ... - Nature.com - February 18th, 2024 [February 18th, 2024]
- Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with ... - Journal of Translational... - February 18th, 2024 [February 18th, 2024]
- Polymerase Chain Reaction (PCR) - National Human Genome Research Institute - February 18th, 2024 [February 18th, 2024]
- Genomic Time Machine Reveals Secrets of Human DNA - SciTechDaily - February 18th, 2024 [February 18th, 2024]
- 1 Million Unannotated Exons Discovered in the Human Genome - Technology Networks - February 18th, 2024 [February 18th, 2024]
- Hope for the night parrot: bird's full genome has been sequenced - Cosmos - February 18th, 2024 [February 18th, 2024]
- RevIT AAV Enhancer: Rev-up AAV genome production in upstream manufacturing - BioProcess Insider - February 18th, 2024 [February 18th, 2024]
- Multi-omics resources for the Australian southern stuttering frog (Mixophyes australis) reveal assorted antimicrobial ... - Nature.com - February 18th, 2024 [February 18th, 2024]
- Large-scale gene expression alterations introduced by structural variation drive morphotype diversification in Brassica ... - Nature.com - February 18th, 2024 [February 18th, 2024]
- Near-gapless and haplotype-resolved apple genomes provide insights into the genetic basis of rootstock-induced ... - Nature.com - February 18th, 2024 [February 18th, 2024]
- Secrets of Night Parrot unlocked after first genome sequenced - CSIRO - February 18th, 2024 [February 18th, 2024]
- CRISPR gene editing tool gets a revolutionary high-tech upgrade - Earth.com - February 18th, 2024 [February 18th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 18th, 2024 [February 18th, 2024]
- Natural selection and genetic diversity maintenance in a parasitic wasp during continuous biological control application - Nature.com - February 18th, 2024 [February 18th, 2024]
- Hopes elusive parrots genome will provide answers - news.com.au - February 18th, 2024 [February 18th, 2024]
- MicroRNA is the master regulator of the genome researchers are learning how to treat disease by harnessing the ... - The Conversation - November 30th, 2023 [November 30th, 2023]
- "Ground-Breaking" Release of World's Largest Whole Genome Resource - Inside Precision Medicine - November 30th, 2023 [November 30th, 2023]
- Pangenome analysis reveals genomic variations associated with domestication traits in broomcorn millet - Nature.com - November 30th, 2023 [November 30th, 2023]
- Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome ... - Nature.com - November 30th, 2023 [November 30th, 2023]
- Genome characteristics of atypical porcine pestivirus from abortion cases in Shandong Province, China - Virology Journal - Virology Journal - November 30th, 2023 [November 30th, 2023]
- Correcting modification-mediated errors in nanopore sequencing by nucleotide demodification and reference-based ... - Nature.com - November 30th, 2023 [November 30th, 2023]
- CRISPR-Based "Genome Shredding" Technique Shows Promise in Treating Glioblastoma - Inside Precision Medicine - November 30th, 2023 [November 30th, 2023]
- Genome wide analysis revealed conserved domains involved in the effector discrimination of bacterial type VI secretion ... - Nature.com - November 30th, 2023 [November 30th, 2023]
- TRISH to investigate the effects of spaceflight on the human genome, central nervous system - Odessa American - November 30th, 2023 [November 30th, 2023]
- The venom preceded the stinger: Genomic studies shed light on the origins of bee venom - EurekAlert - November 30th, 2023 [November 30th, 2023]
- Integrating genomic and multiomic data for Angelica sinensis provides insights into the evolution and biosynthesis of ... - Nature.com - November 30th, 2023 [November 30th, 2023]
- Genetic diversity and ancestry of the Khmuic-speaking ethnic groups ... - Nature.com - September 21st, 2023 [September 21st, 2023]
- Researchers to Apply Genome Analysis to Childhood Cancers; Goal ... - The Japan News - September 21st, 2023 [September 21st, 2023]
- How Bats' Genomes May Help Them Avoid Cancer and Survive ... - Technology Networks - September 21st, 2023 [September 21st, 2023]
- Longitudinal genomic surveillance of carriage and transmission of ... - Nature.com - September 21st, 2023 [September 21st, 2023]
- Whole genomes from bacteria collected at diagnostic units around ... - Nature.com - September 21st, 2023 [September 21st, 2023]
- Genome-wide identification of lncRNA & mRNA for T2DM | PGPM - Dove Medical Press - September 21st, 2023 [September 21st, 2023]
- Tasmanian tiger RNA is first to be recovered from an extinct animal - Nature.com - September 21st, 2023 [September 21st, 2023]
- Loneliness and depression: bidirectional mendelian randomization ... - Nature.com - September 21st, 2023 [September 21st, 2023]
- Rome Therapeutics adds $72 million to Series B round to harness ... - OutSourcing-Pharma.com - September 21st, 2023 [September 21st, 2023]
- Mystery of 'living fossil' tree frozen in time for 66 million years finally ... - Livescience.com - September 21st, 2023 [September 21st, 2023]
- Why the human genome could be healthcares holy grail - Yahoo Finance - May 4th, 2023 [May 4th, 2023]
- Scientists Compare Genomes of 240 Mammals to Understand Human DNA - The New York Times - May 4th, 2023 [May 4th, 2023]
- Genomes From 240 Mammalian Species Help Explain 100 Years Of Evolution And Human Disease - ABP Live - May 4th, 2023 [May 4th, 2023]
- 'Deletions' from the human genome may be what made us human - Yale News - May 4th, 2023 [May 4th, 2023]
- GeneDx Adds Buccal Swab as Non-Invasive Whole Genome ... - GlobeNewswire - May 4th, 2023 [May 4th, 2023]
- Whole-genome sequencing used to track down genes behind familial glioma - Medical Xpress - May 4th, 2023 [May 4th, 2023]
- Wiggly proteins guard the genome: Dynamic network in the pores of ... - Science Daily - May 4th, 2023 [May 4th, 2023]
- Genome-Wide Splicing Quantitative Expression Locus Analysis ... - Cancer Discovery - May 4th, 2023 [May 4th, 2023]
- Digital Genome Market is expand at a CAGR of 8.6% to reach USD ... - Digital Journal - May 4th, 2023 [May 4th, 2023]
- High School Students Learn the Basics of Base Editing to Cure GFP ... - University of California San Diego - May 4th, 2023 [May 4th, 2023]
- Genomic researchers gain access to CSIRO's AI-powered data ... - Microsoft - May 4th, 2023 [May 4th, 2023]
- Archaic hominin traits through the splicing lens - Nature.com - May 4th, 2023 [May 4th, 2023]
- Critical bug in genome sequencing device scores '10' on CVSS ratings - SC Media - May 4th, 2023 [May 4th, 2023]
- Novel Genomic Approach Ensures Better Diagnosis of Hereditary ... - Technology Networks - May 4th, 2023 [May 4th, 2023]
- Intellia Therapeutics: Leading the Way in Revolutionary Genome ... - Best Stocks - May 4th, 2023 [May 4th, 2023]
- Visual tracking of viral infection dynamics reveals the synergistic ... - Nature.com - May 4th, 2023 [May 4th, 2023]
- Genome | Genome LLC | United States - March 31st, 2023 [March 31st, 2023]
- Belarus: EU and WHO deliver equipment for research of genomes of infectious disease agents - EIN News - February 24th, 2023 [February 24th, 2023]
- Gene vs. genome: Definition, function, and impact - January 30th, 2023 [January 30th, 2023]
- Big cog in the wheel: As Covid worries reappear, Insacogs genome sequencing ability must be aided by govts - Times of India - December 25th, 2022 [December 25th, 2022]
- CapitalGainsReport Sector Spotlight: Healthcare Penny Stocks On The Move (ARDX, WHSI, BNGO) - Marketscreener.com - November 25th, 2022 [November 25th, 2022]
- Genome Insight and Kun-hee Lee Child Cancer & Rare Disease Project Team of SNUH (Seoul National University Hospital) Made an Agreement About a... - November 23rd, 2022 [November 23rd, 2022]
- Genome-wide association study reveals distinct genetic associations related to leaf hair density in two lineages of wheat-wild relative Aegilops... - October 19th, 2022 [October 19th, 2022]
- The Global Genomics Market to Exhibit Growth at a CAGR of 16.90% During the Forecast Period (20222027) | DelveInsight - Yahoo Finance - October 19th, 2022 [October 19th, 2022]
- Illumina and GenoScreen Partner to Expand Access to Genomic Testing for Multidrug-Resistant Tuberculosis - PR Newswire - October 19th, 2022 [October 19th, 2022]
- Superresolution Method Poised to Better Gene Function Understanding - Photonics.com - October 19th, 2022 [October 19th, 2022]
- Genome-centric analysis of short and long read metagenomes reveals uncharacterized microbiome diversity in Southeast Asians - Nature.com - October 15th, 2022 [October 15th, 2022]
- How a New Battery Data Genome Project Will Use Vast Amounts of Information to Build Better EVs - InsideClimate News - October 15th, 2022 [October 15th, 2022]
- Scientists Reconstruct the Genome of the 180-Million-Year-Old Common Ancestor of All Mammals - SciTechDaily - October 15th, 2022 [October 15th, 2022]
- Combining OSMAC, metabolomic and genomic methods for the production and annotation of halogenated azaphilones and ilicicolins in termite symbiotic... - October 15th, 2022 [October 15th, 2022]
- Concerted expansion and contraction of immune receptor gene repertoires in plant genomes - Nature.com - October 15th, 2022 [October 15th, 2022]
- Uncovering the Full Variant Continuum with Pioneering Solutions from Bionano - Inside Precision Medicine - October 15th, 2022 [October 15th, 2022]
- Metagenomic analysis of viromes in tissues of wild Qinghai vole from the eastern Tibetan Plateau | Scientific Reports - Nature.com - October 15th, 2022 [October 15th, 2022]
- Research Assistant in Molecular and Genome Editing Therapeutics job with KINGS COLLEGE LONDON | 311876 - Times Higher Education - October 15th, 2022 [October 15th, 2022]
- Lessons learnt from COVID-19 shed light on future pandemic preparedness - The Peter Doherty Institute for Infection and Immunity - October 15th, 2022 [October 15th, 2022]
- From Neanderthal genome to Nobel prize: meet geneticist Svante Pbo - Nature.com - October 8th, 2022 [October 8th, 2022]
- Revealing the genome organization of the earliest common ancestor of all mammals - Tech Explorist - October 8th, 2022 [October 8th, 2022]
- Mitochondrial DNA Is Working Its Way Into the Human Genome - Technology Networks - October 8th, 2022 [October 8th, 2022]
- Animated Map: Where to Find Water on Mars - Visual Capitalist - October 8th, 2022 [October 8th, 2022]
- Reconstruction of The First Mammal's Genome Suggests It Had 38 Chromosomes - ScienceAlert - October 6th, 2022 [October 6th, 2022]
- Genomic Science Breakthroughs Are Happening Faster Than Ever Thanks to HPC - CIO - October 6th, 2022 [October 6th, 2022]
- Genome Of Ancient Humans Is The Winning Field Of 2022's Nobel Prize in Medicine - IFLScience - October 6th, 2022 [October 6th, 2022]
- ASU professor to study new genome editing tools with NIH Innovator Award - ASU News Now - October 6th, 2022 [October 6th, 2022]
- New R&D norms to fast-track research on genome-edited crops - The Financial Express - October 6th, 2022 [October 6th, 2022]