FIELD NOTES

Chris Anderson our Senior Editor gives a roundup of the recent developments in the precision medicine field.

REDWOOD CITY, Calif. – In late winter at the Advances in Genome Biology and Technology(AGBT) scientific meeting in Marco Island, Fla., a coalition of 13 life science and diagnostics companies announced the formation of the Allele Frequency Community, a data gathering and sharing initiative formed to improve the interpretation of sequencing data in both clinical and research settings.

To launch the community, the organizations

agreed to pool their extensive exome- and

genome-wide variant call data sets in an

anonymized, pooled fashion to create the most

ethnically diverse, freely-accessible, database

of allele frequencies currently available. Allele

frequency has become increasingly important

tool to help in the interpretation of human

variation, but diagnostic labs and clinicians

have been hampered by access to limited

datasets on allele frequency within a population.

“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, a founding member of the

community. “By combining data from many

organizations, we can get far more sensitive

measurements of allele frequencies. It’s

something we can only do together.”

By pooling the data and making it available

from one source, clinicians stand to gain

insight into the significance of particular

alleles and help them better determine

how common some variations are within a

population, which in turn helps them distinguish

rare, disease-causing variants from more

common variations. “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 underrepre-

sented in existing public databases,” added Dr.

Heidi Rehm, PhD, director of the laboratory

for molecular medicine at Partners Healthcare

Personalized Medicine.

At the time of its formation, the Allele

Frequency Community database held more

than 70,000 variant call data sets, spanning

more than 100 countries of origin and 8,000

whole genomes. In the few shorts months

since its founding, new members to the

community have increase that number to more

than 100,000 call sets. An internal benchmarking

study showed that using the original data

sets provided a 43 percent reduction in false

positive rates in causal variant identification,

rates that should continue to improve as more

variant call data sets are added.

“One of the key challenges confronting

precision medicine today is context,” explained

Dr. Doug Bassett, Vice President Translational

Research and Chief Scientific Officer at QIAGEN

Bioinformatics, which is providing the secure

hosting for the data. “When interpreting the

human genome, you want to know as much

about the variants in that genome as possible,

including whether any have been associated

with disease or simple elements like how

common they are. Understanding this can

help guide treatment and suggest new areas

of disease research.”

To encourage growth of the resource, users

can choose to opt-in to the community. As

a condition of opting in, new members agree

to contribute information from their sequences

to the community resource. To protect patient

privacy, only anonymous, pooled allele

frequencies are provided. A global resource,

Bassett said they are hopeful that the community

can add allele information from ethnic

populations that are currently underrepresented

in public databases, noting that most of that

data skews toward North American and European

populations.

For more information on the Allele Frequency

Community and how to participate visit

www.allelefrequencycommunity.org.

Adding value to allele data

QIAGEN on behalf of the Allele Frequency community

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