Allele
Frequency
Community

Co-founders


Stan Letovsky & Thomas Kaminskikaminski-letovsky

Associate VP for clinical bioinformatics & General manager, Enlighten Health Genomics (division of LabCorp)

“When we’re interpreting variants, especially variants of unknown significance, the more data we have the greater the likelihood that we have seen that variant before and may have something to say about it,” said Stan Letovsky, associate vice president for clinical bioinformatics at LabCorp. “The Allele Frequency Community presents a great opportunity for labs to pool resources in a precompetitive way for broad benefit.”

“At LabCorp, our biggest strengths are the scale and reach that we have. If we can contribute to a broader initiative that will better characterize the population, then everybody benefits,” said Thomas Kaminski, general manager of Enlighten Health Genomics, a division of LabCorp. “As a commercial lab, this is a great way we can help advance the science in this space.”

Allele Frequency Community
Founding Member Snapshot: LabCorp

Who: Thomas Kaminski, general manager of Enlighten Health Genomics, and Stan Letovsky, associate vice president for clinical bioinformatics at LabCorp

Where: LabCorp

Why: Dealing with rare variants is a real challenge when it comes to delivering important results to physicians and patients. “When we’re interpreting variants, especially variants of unknown significance, the more data we have the greater the likelihood we have seen that variant before and may have something to say about it,” says Letovsky. “This will allow us to get a better survey of allele frequencies in the communities we’re actually serving.”

Value: Kaminski notes the importance in making sequencing data more meaningful for translational work. “At the end of the day, hopefully this will continue to increase the diagnostic rate of sequencing in clinical practice,” he says. “As a commercial lab, this is a great way we can help advance the science in this space.”

What’s next: Letovsky believes that phenotypic data could make a useful addition to genetic databases in the future, and hopes that resources like the Allele Frequency Community can help pave the path among members. “Once you’re collaborating on one thing it can be easier to share other information as well,” he says.

 


 

Peter van der SpekPeter van der Spek

Professor, head of bioinformatics department
Erasmus University Medical Center (Erasmus MC)

“We are very proud to be among the founding members of the Allele Frequency Community. In addition to the very important goal of providing allele frequency information to help scientists and clinicians efficiently get to the most promising variant candidates, we believe this community will help unite institutions and link scientists around the world.”

Allele Frequency Community
Founding Member Snapshot: Erasmus MC

Who: Peter van der Spek, professor and head of the bioinformatics department

Where: Erasmus University Medical Center

Why: Van der Spek sees an immediate need for genetic information about ethnic populations that are underrepresented in existing databases. For instance, more than half of all people living in Rotterdam, which has the second largest port in the world, were not born in the Netherlands. Even excellent Dutch databases don’t have enough data from other populations to help with the interpretation of variants for people born outside the country. “That’s why we are very enthusiastic about participating in the Allele Frequency Community,” he says.

Value: At Erasmus MC, attention has moved to whole genome studies to learn as much as possible about each person — but that means even more variants need to be interpreted. “Having allele frequency data helps in efficient filtering to get to the most promising candidates. For clinical purposes, we only want to pursue the most likely disease-causing variants,” van der Spek says.

Also important: “Data in the Allele Frequency Community is fully anonymous so it protects the patients’ privacy,” he adds.

What’s next: In the coming years, van der Spek hopes to see methylation data added to genetic databases.

 


 

Eric Schadteric_shadt_050_web

Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai

“This resource will enable a much more accurate interpretation of genomes by aiding in the identification and prioritization of variants that predispose an individual to a disease or explain a protective phenotype,” said Eric Schadt, Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai. “Assembling allele frequency information in a comprehensive fashion over many different populations is a critical element of genome interpretation, and making it available as a public resource is the right way to do it.”

Allele Frequency Community
Founding Member Snapshot: Icahn Institute for Genomics and Multiscale Biology at Mount Sinai

Who: Eric Schadt, Director

Where: Icahn Institute for Genomics and Multiscale Biology at Mount Sinai

Why: Understanding allele frequencies across diverse populations will be important for making sense of genomic information. “Assembling allele frequency information in a comprehensive fashion over many different populations is a critical element of genome interpretation,” Schadt says. “This resource will enable a much more accurate interpretation of genomes by aiding in the identification and prioritization of variants that predispose an individual to a disease or explain a protective phenotype.”

Value: By pooling anonymized data, the Allele Frequency Community will enable much higher-powered studies than would otherwise be possible. Schadt says scientists currently encounter a hodgepodge of cohorts that have enough sequencing information to calculate allele frequencies, but they are typically small and only represent one or two ethnicities. “There is no harmonized way of generating allele frequency information across all available cohorts,” Schadt says. “The Allele Frequency Community is taking on the lion’s share of that work.”

Also important: Making these data publicly available ensures that scientists will no longer have to painstakingly generate this kind of information on their own.

What’s next: Schadt believes the long-term benefits of the Allele Frequency Community may be ones we can’t even conceive of today. “Having all of this information assembled in one place, harmonized, and publicly available may lead to discoveries and ways of using those data that we can’t necessarily anticipate today because it doesn’t exist in that kind of way,” he says.

 


 

Heidi RehmHeidi 2007_026

Director of the Laboratory for Molecular Medicine at Partners Healthcare Personalized Medicine and Associate Professor of Pathology at Harvard Medical School

“Over the last few years access to allele frequency data from large populations has been the most useful resource for the interpretation of human variation,” said Heidi Rehm, director of the Laboratory for Molecular Medicine at Partners Healthcare Personalized Medicine. “The Allele Frequency Community is a really valuable project. I am happy to share data through this new resource and excited that many other people have agreed to do so as well.”

“A share-and-share-alike approach will encourage not just the broadest sharing, but also the broadest utility of these data,” said Heidi Rehm, director of the Laboratory for Molecular Medicine at Partners Healthcare Personalized Medicine. “Researchers can use this information to get a reasonable sense of the allele frequency in a population and perhaps quickly eliminate variants that are common in ethnic populations that may be underrepresented in existing public databases.”

Allele Frequency Community
Founding Member Snapshot: Partners Healthcare

Who: Heidi Rehm, director of the Laboratory for Molecular Medicine

Where: Partners Healthcare Personalized Medicine and Harvard Medical School

Why: Rehm says that allele frequency information is increasingly important for the interpretation of human variation. She joined the Allele Frequency Community because “expanding resources to inform allele frequency for populations is a really valuable project.”

Value: “Researchers can use this information to get a reasonable sense of the allele frequency in a population and perhaps quickly eliminate variants that are common in ethnic populations that may be underrepresented in existing public databases.”

Also important: “A share-and-share-alike approach will encourage not just the broadest sharing, but also the broadest utility of these data.”

What’s next: In the coming years, Rehm hopes that efforts like this expand to include phenotypic data and cohort data.

 


 

Jay Shendurejay_shendure

Associate Professor of Genome Sciences, University of Washington

“There are myriad groups generating large amounts of sequencing data and one challenge has been finding ways to translate the data-sharing ethos of genomics into this new world where issues around data privacy are much more relevant,” said Jay Shendure, Associate Professor of Genome Sciences at the University of Washington. “Ideally we would have a system that allows us to get the best of both worlds: protecting the privacy of individual data while sharing aggregated information across diverse institutions in a crowdsourcing model.”

“Getting to the population sizes needed to define the allele frequencies of rare variants is something individual labs, institutions, or commercial entities can rarely achieve on their own,” said Jay Shendure, Associate Professor of Genome Sciences at the University of Washington. “By combining data from many organizations, we can get far more sensitive measurements of allele frequencies. It’s something we can only do together.”

Allele Frequency Community
Founding Member Snapshot: University of Washington

Who: Jay Shendure, Associate Professor of Genome Sciences

Where: University of Washington

Why: While countless groups are generating sequencing data, sharing information that may have been generated from patient samples is a real challenge. Shendure believes that a framework to enable sharing of aggregated data while still protecting the privacy of patient information is a critical step forward.

Value: “Getting to the population sizes needed to define the allele frequencies of rare variants is something individual labs, institutions, or commercial entities can rarely achieve on their own,” Shendure says. “By combining data from many organizations, we can get far more sensitive measurements of allele frequencies. It’s something we can only do together.”

Also important: Shendure says recent attention for precision medicine underscores the need for this kind of community effort. “There’s an enormous amount of interest in finding ways to take advantage of all of this data that has been generated to advance patient care and research while still keeping data confidential.”

What’s next: Shendure hopes the Allele Frequency Community framework could eventually be expanded to phenotypic data to help with high-powered genetic analyses for complex traits. “This is heading in the direction of facilitating cross-institutional genetic data aggregation to drive discovery,” he says.

 


Gustavo GlusmanGustavo Glusman

Senior Research Scientist, Institute for Systems Biology

“What I see as the most important value of the Allele Frequency Community is taking knowledge from a large population of genomes and extracting information that improves the annotation of each individual genome,” said Gustavo Glusman, senior research scientist at the Institute for Systems Biology. “At ISB, we’re aiming at P4 medicine — predictive, preventive, personalized, and participatory — and improving genome annotation is critical for that.”

Who: Gustavo Glusman, Senior Research Scientist

Where: Institute for Systems Biology Why: “Allele frequency information is one of the key tools in the toolbox,” says Glusman, who in 2010 created a database called Kaviar that integrated publicly available datasets to get at this kind of information. “Is a variant novel? How rare might it be? So many types of analysis are based on those questions, and the Allele Frequency Community is going to improve those analyses.”

Value: “One very important thing is the representation of all kinds of populations. Right now the databases have an extremely strong bias toward Caucasian genomes,” Glusman says. “The more genomes, the better for reliable estimates of variant frequencies.”

Also important: As Glusman has learned, it can be very difficult for individual scientists to share even pieces of private datasets with each other. “QIAGEN Bioinformatics has the advantage of being a neutral broker,” he says. “A major advantage of the Allele Frequency Community is that it enables people to share their data more easily, with just the click of a button for genomes they’ve already uploaded.”

What’s next: “At some point, we’ll have such a good understanding of allele frequencies that we’ll need better estimates of frequencies for different phenotypes and diseases,” Glusman says.

 


 

Christopher Masonchris mason

Assistant Professor in the Institute for Computational Biomedicine Weill Cornell Medical College

“The ability to differentiate between a mutation you might expect to see by chance and a mutation that is potentially disease-causing requires context from as many genomes as possible,” said Christopher Mason, assistant professor in the Institute for Computational Biomedicine at Weill Cornell Medical College. “With the Allele Frequency Community, you immediately get access to hundreds of collaborators who are sharing this data openly and transparently. It’s a big step forward.”

Allele Frequency Community
Founding Member Snapshot: Weill Cornell Medical College

 

Who: Christopher Mason, Assistant Professor in the Institute for Computational Biomedicine

Where: Weill Cornell Medical College

Why: “Allele frequency information is essential for large-scale data analysis and for contextualizing one genome or thousands of genomes,” Mason says. “The Allele Frequency Community gets us closer to having a sense of all of the mutations that are in the world.”

Value: Mason recalls his postdoc days, when getting control samples involved going to neighboring labs and requesting access to their cohorts. “With the Allele Frequency Community, you essentially get an ocean of collaborators just by taking one step into the water,” he says. “It’s the equivalent of knocking on the doors of dozens of labs.”

Also important: The community’s sharing philosophy will accelerate research and interpretation. Sharing makes it easier and more scalable to analyze genomes and put variants in context, Mason says.

What’s next: Down the road, Mason hopes to share epigenetic data as well. “We’ve done targeted and global methylation profiling and the same question arises there as well,” he says. “When we see regions of the genome that are dynamically modulated for epigenetic reasons, is this part of normal biological noise or is this actually something relevant to my phenotype?”


 

Co-founders list

  1. QIAGEN Bioinformatics, 1700 Seaport Blvd, Third Floor, Redwood City, CA, 94063, USA
  2. Children’s Hospital of Eastern Ontario (CHEO), 401 Smyth Road, Ottawa, Ontario K1H 8L1
  3. Stanford School of Medicine, 291 Campus Drive, Stanford, CA 94305-5101 USA
  4. Cardiff University School of Medicine, Cardiff CF14 4XN
  5. Inova Translational Medicine Institute, 8110 Gatehouse Road, Falls Church, VA, 22042, USA
  6. Institute for Systems Biology, 401 Terry Avenue North, Seattle, WA, 98109, USA
  7. Columbia University Institute for Genomic Medicine, 630 West 168th St New York, NY 10032, USA
  8. Emory Genetics Laboratory, 2165 N Decatur Rd, Decatur, GA , 30033, USA
  9. University of British Columbia, 2329 W Mall, Vancouver, BC, V6T 1Z4, Canada
  10. Enlighten Health Genomics, a business of Laboratory Corporation of America® Holdings (LabCorp®), T W Alexander Drive, Research Triangle Park, North Carolina 27709, USA
  11. HudsonAlpha, 601 Genome Way, Huntsville, AL 35806 USA
  12. Weill Cornell Medical College, 1305 York Ave, New York, NY 10021, USA
  13. New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA
  14. Harvard Medical School and Brigham & Women’s Hospital, 65 Landsdowne Street, Cambridge, MA , 02139, USA
  15. Imago Biosciences, San Francisco, California, USA
  16. Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA
  17. University of Washington, 3720 15th Ave NE, Seattle, WA, 98195, USA
  18. Erasmus University Medical Center, 3000 CA , Rotterdam, The Netherlands

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