By Julia Karow
This article has been updated from a previous version to attribute Ambry's comments to the company's assistant medical director.
23andMe and Ambry Genetics both said last week that they are rolling out exome sequencing services for individuals. While direct-to-consumer firm 23andMe is launching a pilot program for existing customers, providing them with exome data but no interpretation, clinical diagnostic company Ambry is offering exome sequencing for the diagnosis of patients with "severe unexplained conditions."
The companies are among the first to provide exome sequencing for individuals rather than research studies, although personal whole-genome sequencing has already been offered for several years by Illumina and Knome.
23andMe: Exome 80x
23andMe expects to provide exome sequence data to customers approximately four months after shipping their samples to a laboratory, but many details of the pilot program, including the laboratory partner, are not yet available
The firm will offer the new service, called "Exome 80x," to a limited number of its current customers at a price of $999 and will be taking first orders "soon" (CSN 9/28/2011).
Customers will obtain raw data of about 50 million bases, sequenced at 80x coverage, but no interpretation. Over time, 23andMe plans to offer "new tools and content" to "take advantage" of the exome data.
According to a company spokesperson, such reports and features "may" become available over time as the company "learns more about what exome data can tell us," but there is currently no timeline.
Like 23andMe's existing genotyping service, Exome 80x does not require a prescription from a physician.
The company acknowledged that the pilot is not suitable for every customer but geared at early adopters "who are comfortable managing and understanding raw genetic data."
The company will sequence the exomes of participating customers in batches, not as soon as they are received, and it expects to provide them with raw data in about four months "once batches are submitted to the laboratory," according to the spokesperson. Customers can download their data in the form of standard variant files.
The company is still finalizing details of the program and will not be providing for a number of weeks information such as the exome capture method, the sequencing platform, the type of laboratory it will be outsourcing the work to, the number of participants it is seeking, or the duration of the program.
However, the fact that it plans to provide customers with 50 megabases of raw data indicates that it might be using the Agilent SureSelect Human All Exon 50 Mb platform, since competing exome enrichment platforms from Roche NimbleGen and Illumina target smaller and larger amounts of DNA, respectively.
Up until now, 23andMe has been offering an array-based genotyping service, called the Personal Genome Service, that analyzes about a million SNPs throughout the genome and is currently priced at $99. For PGS, the company provides more than 200 reports that link genetic variants to health conditions, traits, and ancestry.
Exome 80x marks the company's first move from genotyping to DNA sequencing, though it is already hinting this is only a step on the way to whole-genome sequencing. The exome pilot project "makes a significant advancement toward making full sequencing available for a reasonable price," the spokesperson said, and the project will "help shape our understanding of the information the exome can offer as well as the level of interest there is for exome sequencing data."
The company also wants to use data from the exome pilot "as a basis of comparison and validation for the current genome-wide associations" from its chip-based genotyping data. It currently has no plans to extend the exome service beyond the pilot project, the spokesperson said.
Ambry: Clinical Diagnostic Exome
Unlike 23andMe's offering, Ambry Genetics' Clinical Diagnostic Exome test is geared at patients with undiagnosed or difficult-to-diagnose genetic disorders, and is not offered directly to consumers.
The test requires a medical prescription, and patients will have to review an exome-specific consent form with their physician. The company will be sequencing patients' exomes in its CLIA-certified and CAP-accredited laboratory, using Agilent's SureSelect Human All Exon 50 Mb kit and Illumina's HiSeq 2000 next-gen sequencer. It will sequence the exomes at a minimum average coverage of 50x.
Ambry will also provide a clinical interpretation of the results. To that end, it has built a bioinformatics pipeline that creates a short list of candidate genes that will be further interpreted by its medical staff. The pipeline contains "data from hundreds of exome samples" and has been "vigorously validated by numerous internal and external benchmark data," according to Elizabeth Chao, Ambry's assistant medical director, who provided comments via e-mail.
The company plans to disclose pricing for the test at the American Society of Human Genetics annual meeting this month. Its standard pricing will be for exome sequencing of three samples — that of the patient and two of his or her relatives — as well as the bioinformatics analysis and medical interpretation.
The service can be ordered immediately, and Ambry said it has already seen interest from its clients. Besides diagnostic exome sequencing, it offers exome sequencing in its CLIA lab for use in translational research and discovery.
As companies like 23andMe and Ambry are starting to move exome sequencing beyond the research lab, prices for exome sequencing services are declining.
Axeq Technologies, for example, provides 80x exome sequencing at a promotional price of $1,900, with a minimum order volume of six samples. According to the company's website, this promotion, which expired Sept. 30, includes exome enrichment using Illumina TrueSeq or NimbleGen EZ, paired-end sequencing to 75x-80x coverage on Illumina's HiSeq 2000 with guaranteed average 30x on-target coverage, and SNP and indel calling.
For $9,000, Axeq offers exome sequencing of three samples — patients and their parents — as well as bioinformatics analysis to researchers. The analysis includes SNP and indel calling; filtering of variants and comparisons between affected individuals and controls; and a list of candidate genes with extensive annotations.
China's BGI, on the other hand, offers exome sequencing "starting at" $999, according to its website. BGI's service includes exome capture on the Agilent SureSelect or NimbleGen Seq Cap EZ platforms, sequencing on the Illumina HiSeq 2000, and bioinformatics analysis, which comprises variant detection and annotation.
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