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Powering Diverse Population Genomics with the All of Us + AnVIL Imputation Service

Cloud-native, scalable imputation from Broad Clinical Labs

The All of Us + AnVIL Imputation Service helps researchers turn lower-cost genotype array data into richer datasets by filling in missing genetic information using one of the largest and most ancestrally diverse reference panels currently available.

Designed for population genomics and translational research workflows, the service combines large-scale genomic reference data, secure cloud-native infrastructure, and integrated QC, phasing, and imputation workflows. Researchers can leverage these tools without requiring an All of Us registration, and without the need to manage local infrastructure, maintain complex pipelines, or assemble reference panels. 

Automated upfront quality control mitigates common execution errors, such as malformed inputs or reference mismatches, by detecting issues within 30 minutes. By intercepting these anomalies prior to job execution, the service protects research budgets and optimizes timelines against unproductive cloud compute spend.

The service runs within Terra’s FedRAMP Moderate-authorized environment, supporting the secure processing of genomic research data while keeping the protected reference panel inaccessible to users.

For researchers ready to evaluate the service, the first 2,500 samples submitted are currently available at no cost — making it easier to test performance, assess fit, and bring imputation into existing genomic workflows.

A panel built for diverse ancestry, at population scale

By bringing together 515,579 reference genomes and broad ancestry representation, the All of Us + AnVIL reference panel helps researchers expand lower-cost array data into richer genomic datasets for population genomics, translational research, and precision medicine studies.

Other highlights include: 

Scientific validation

Broad Clinical Labs performed preliminary validation studies using Global Diversity Array (GDA) data from 42 ancestrally diverse participants with matched 30X whole genome sequencing (WGS) data generated at the Broad Institute.

Imputation results from the All of Us + AnVIL Imputation Service were validated directly against the 30X WGS baseline. In preliminary analyses, the service demonstrated high imputation confidence (R²) across a wide range of  allele frequencies and ancestry groups, showing notable strengths in SNP and indel imputation within several non-European populations.

These findings underscore the importance of ancestry representation in reference panel design and imputation performance.

From array data to analysis-ready results

The service is designed to simplify genotype imputation for research teams by bringing sample submission, quality control, phasing, imputation, notification, and result delivery into a single workflow.

Researchers can submit hg38 array data and receive analysis-ready outputs without managing local infrastructure, pipelines, or reference panels.

Built for research teams working at scale

The All of Us + AnVIL Imputation Service is designed for teams generating or analyzing array-based genomic data across population-scale and translational research programs.

The service may be especially useful for researchers working on:

  • GWAS, meta-analyses, and cohort harmonization
  • Polygenic risk score discovery, validation, and portability
  • Large-scale biobank and cohort studies
  • Clinical trial, biomarker discovery, and translational research workflows
  • Projects that need secure and managed workflows for QC, phasing, imputation, and result delivery

Learn more

Ready to test the All of Us + AnVIL Imputation Service with your own array data?

The first 2,500 samples submitted through the service are currently available at no cost, giving research teams a practical way to evaluate performance, assess fit, and bring imputation into existing genomic workflows.

Contact us to discuss your project, ask questions, or get started with your first submission.

Service portal: https://allofus-anvil-imputation.terra.bio/
Help center: https://broadscientificservices.zendesk.com/hc/en-us/

This work was made possible through NIH-supported programs including the All of Us Research Program and NHGRI AnVIL.

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Sean Hofherr

Chief of Clinical Strategy and Product Development, Broad Clinical Labs

Sean Hofherr is dual board certified by ABMGG in Clinical Biochemical Genetics and Clinical Molecular Genetics. Sean serves as the Chief of Clinical Strategy and Product Development at Broad Clinical Labs. In this role at BCL, Sean is able to leverage his extensive experience to guide the clinical vision and delivery across the organization. Sean most recently served as the Chief Operating Office at Fabric Genomics, which focuses on the use of AI and Bioinformatics for Clinical Interpretation of whole genome sequencing. Prior to Fabric, Sean was the Chief Scientific Officer and CLIA Director at the commercial reference laboratory, GeneDx.

Sean received his B.S. degree in Microbiology and Cell Sciences from the University of Florida before earning his Ph.D. in Molecular and Human Genetics from Baylor College of Medicine. Sean completed clinical fellowships in Clinical Biochemical Genetics and Clinical Molecular Genetics at the Mayo Clinic.

Danielle Perrin

Chief of Staff, Broad Clinical Labs

As Broad Clinical Labs’ Chief of Staff, Danielle Perrin advises and supports colleagues on the executive leadership team in BCL’s strategic planning and execution. She builds and leads new organizational functions and processes and leads critical projects, as well as driving effective information flow, decision making, and execution throughout the organization. An operations leader with a business, engineering, and biology background and 20+ years of experience in the genomics field, Perrin has a track record of driving operational excellence and building and scaling both physical and business processes. During her career at Broad, which started in 2003 at the tail end of the Human Genome Project, Perrin has led laboratory operations and R&D teams in Broad’s Genomics Platform, as well as fulfilling senior advisory and leadership roles in the Broad Institute’s COO and CFO offices.

Perrin received her B.S. in Biology and M.E. in Biotechnology Engineering from Tufts University and her M.B.A. from the MIT Sloan School of Management.

Tim De Smet

Chief Commercial Officer, Broad Clinical Labs

As Chief Commercial Officer of Broad Clinical Labs, Tim De Smet leads BCL’s business development, alliance management, external project management, and customer support teams. A Broad Institute employee since 2008, De Smet has held leadership roles and managed teams of various sizes in Broad’s Genomics Platform and clinical lab, spanning laboratory operations, finance, and informatics, and has expertise in work design, financial modeling, and high scale laboratory and business operations.

De Smet received his B.S. in Biochemistry and M.B.A. from Northeastern University.

Jim Meldrim

Chief Technology Officer, Broad Clinical Labs

As Chief Technology Officer, Jim Meldrim sets the vision for Broad Clinical Labs’ informatics systems, including the hardware and software used for sample intake and tracking, data production, analysis, and delivery. Having held a variety of laboratory and informatics-focused leadership roles at Broad, spanning R&D and production operations, Meldrim has been a leader and innovator in the generation, management, and analysis of genomic data since 1999, beginning with sequencing data generation for the Human Genome Project.

Meldrim received his B.S. in Biology from Cornell University.

Sheila Dodge

Chief Operating Officer, Broad Clinical Labs

As Chief Operating Officer, Sheila Dodge leads Broad Clinical Labs’ process development and implementation activities, as well as lab operations, financial planning and operations, quality & compliance, and core business processes. A Six Sigma Black Belt with extensive experience in process development and high throughput genomics operations, Dodge is an expert in work design and in collaborating with a range of collaborators, scientists, engineers, and technology partners to rapidly integrate new technologies and operationalize innovations. A member of the Broad Institute since 2001, Dodge is an Institute Scientist and lectures at the MIT Sloan School of Management on operations, dynamic work design, and visual management techniques.

Dodge received her B.A. in biochemistry and molecular biology from Boston University and her master’s degree in biology from Harvard University. She earned her M.B.A. from MIT Sloan School of Management.

Heidi Rehm, Ph.D., FACMG

Chief Medical Officer and Clinical Laboratory Director, Broad Clinical Labs

Heidi Rehm is board-certified by ABMGG in Clinical Molecular Genetics and Genomics and serves as BCL’s Chief Medical Officer and Clinical Laboratory Director. She oversees BCL’s regulatory requirements, leads the clinical team performing genomic interpretation and variant analysis, and guides BCL’s efforts in genomic testing for clinical and research use. She is also an Institute Member of the Broad and co-director of the Medical and Population Genetics Program. Rehm is also the Chief Genomics Officer in the Department of Medicine and Genomic Medicine Unit Director at the Center for Genomic Medicine at Massachusetts General Hospital, working to integrate genomics into medical practice. She is a principal investigator of ClinGen, providing free and publicly accessible resources to support the interpretation of genes and variants. She co-leads both the Broad Center for Mendelian Genomics, focused on discovering novel rare disease genes, and the Matchmaker Exchange, which aids in gene discovery. She is Chair of the Global Alliance for Genomics and Health, a principal investigator of the Broad-LMM-Color All of Us Genome Center, co-leader of the Genome Aggregation Database (gnomAD), and a Board Member and Vice President of Laboratory Genetics for the American College of Medical Genetics and Genomics.

Rehm received her B.A. degree in molecular biology and biochemistry from Middlebury College before earning her M.S. in biomedical science from Harvard Medical School and Ph.D. in genetics from Harvard University. She completed her post-doctoral training with David Corey in neurobiology and a fellowship in clinical molecular genetics at Harvard Medical School.

Niall Lennon, Ph.D.

Chair and Chief Scientific Officer, Broad Clinical Labs

As Chair and Chief Scientific Officer of Broad Clinical Labs, Niall Lennon leads the team and sets the scientific and clinical vision for the organization. Dr. Lennon joined the Broad Institute in 2006 and has since contributed to the development of applications for every major massively parallel sequencing platform across a range of fields. In 2013 Dr. Lennon led the effort to establish a CLIA licensed, CAP-accredited clinical laboratory at the Broad Institute to facilitate return of results to patients and to support clinical trials. More recently, he has led efforts to achieve FDA approval for large-scale genomics projects (NIH’s All of Us Research Program) and for Broad’s own clinical diagnostic for COVID-19 testing operation, which returned 37+ million results to patients. Dr. Lennon is a principal investigator of the eMerge and All of Us projects, an Institute Scientist at Broad, Associate Director of Broad’s Gerstner Center for Cancer Diagnostics, and an adjunct professor of biomedical engineering at Tufts University, where he teaches Molecular Biotechnology.

Dr. Lennon received a Ph.D. in pharmacology from University College Dublin and completed his postdoctoral studies at Harvard Medical School and Massachusetts General Hospital. He holds an executive certificate in management from the MIT Sloan School of Management.