SAN FRANCISCO (GenomeWeb) – Dante Labs, which has been providing direct-to-consumer whole-genome sequencing and analysis services through partner labs, is in the process of bringing sequencing capabilities in house.
Starting in July, the company plans to begin moving sequencing to its own laboratory, based in L'Aquila, Italy, where it has already installed Oxford Nanopore Technologies' PromethIon system and plans to deploy either Illumina or MGI instruments, according to CEO Andrea Riposati. The company aims to have ISO and CLIA certifications as well as CAP accreditation for its lab by the first or second quarter of next year, he said.
The firm launched in 2017, originally offering a handful of DTC sequencing-based tests, including for hereditary cancer and cardiovascular disease, for customers in Europe.
Since then, it has revised its business model from disease-specific tests to whole-genome sequencing and now ships its saliva collection kits globally. Riposati said the company anticipates sequencing around 10,000 samples this year.
While the firm remains focused on the DTC market and anticipates that the vast majority of its sequencing tests will be for consumers, it has also partnered with a clinic in L'Aquila to make its sequencing services available to patients there, and Riposati said that it planned to forge similar partnerships with other clinics in Europe. The partnership is currently in a pilot phase that is looking at how to introduce whole-genome sequencing into the standard of care, Riposati said.
Dante is also looking at the possibility of moving into the research space. It plans to open an office in Finland in the second half of the year that will focus on data analytics for drug discovery for specific diseases, Riposati said. Also, earlier this year, it launched an epilepsy study with the goal of using sequencing to find new drug targets.
The impetus to switch from outsourcing to in-house sequencing was twofold, Riposati said. One factor was that the company's orders have increased. "One year ago, we didn't have the volumes to have our own sequencing lab, but now we have the samples to sequence in-house more efficiently."
Moving the sequencing in-house will give it more control over the process, helping to avoid some of the issues it has experienced over the last couple of years. Last year, for instance, a number of customers experienced significant delays in getting results back, Riposati said. In addition, a handful of customers received used kits in the mail. The company has since switched fulfillment centers and used the experience "as a way to improve," he said. He noted, however, that the mistake did show the strength of Dante's privacy protections, as there was no customer information in the kits, and no one's privacy was breached.
The company has also shifted its approach from specific tests — for hereditary cancer or cardiovascular disease, for instance — to whole-genome sequencing. It now offers three basic versions of whole-genome sequencing: Whole GenomeZ, which includes 130x coverage of coding regions and 30x coverage of noncoding regions, plus mitochondrial genome sequencing, for $899; My Full DNA, a 30x whole genome for $649; and Whole GenomeL, a 30x long-read whole genome sequenced on the PromethIon for $999.
With each test, the consumer receives a health condition report, a wellness and longevity report, a pharmacogenomics report, and a customized report, as well as a link to download the VCF file. Dante has partnered with Sequencing.com to provide the wellness and longevity report and Dante's bioinformatics team generates the other reports. Turnaround time is around 10 to 12 weeks.
The long-read sequencing option on the PromethIon provides information on structural and copy number variants, Riposati said, "which we think is very interesting, especially for neurological diseases." Longer term, the company is looking into the possibility of using long reads to create reference genomes, he said.
For the customized and health condition report, users select specific conditions of interest. The health condition report, for instance, contains information about hereditary conditions, while for the customized report, users can select specific areas of concern, such as epilepsy or cardiovascular disease.
While consumers do not need a doctor's prescription to order the test, Dante recommends that users share their results with a physician, particularly in the case where variants of concern are identified.
Riposati estimated that about half of its customers order testing for a specific reason, either because they have a family history of a genetic condition or because they themselves have an unexplained condition that doctors have suspected to be genetic, but for which they have not been diagnosed. Those customers are very savvy about genetics, he said.
Many customers order tests from Dante because they have a suspected genetic disorder but have been unable to obtain comprehensive testing through traditional routes or have found such testing to be cost prohibitive, Riposati said.
For example, he described one customer from the UK who had already received many single-gene and panel-based tests for his disorder, all of which had been negative. Whole-genome sequencing through Dante identified a variant indicative of Noonan syndrome. The patient then went to his doctor, who ordered a blood analysis, which confirmed the finding. In that case, the PGx report also contraindicated the therapy the patient was on, allowing the physician to adjust it, Riposati said.
He described another customer in Europe who had asked for a report on periodic paralysis and other muscular diseases. In doing the analysis, Dante identified a variant that was related to Brugada syndrome, a heart rhythm disorder. The patient took that result to her doctor, who ran an electrocardiogram, which diagnosed her with Brugada syndrome. In addition, further investigation into the patient's family history revealed a relative who had heart problems, but for whom a diagnosis had never been made.
Riposati said Dante Labs is fully compliant with different countries' genetic testing regulations and because of that does not offer every report in every country. Anyone around the world can order the kit and receive back the raw sequencing data or VCF file, which they can upload to sites like Sequencing.com for analysis. But, for instance, in the US, Riposati said, the firm does not provide more complex analyses, like PGx reports or diagnostic information. Often, Riposati noted, if a customer is ordering the test for a specific reason, to try and find an answer to his or her potential rare genetic disease, they order an analysis based on their symptoms — like periodic paralysis, for instance. Dante can provide back in its report a list of the variants found in that gene set, as well as the VCF file for the entire genome, and that patient can then take the report to a specialist.
In the future, Riposati said, the company is exploring options that include working with doctors in the US, in a model similar to Color Genomics, which provides hereditary cancer testing. It is also considering working with the US Food and Drug Administration, he added.
"We think people should have access to genetic tests," Riposati said.
Dante's sequencing service providers all have ISO certification and are CLIA-certified, CAP-accredited, and compliant with the EU's General Data Protection Regulation.
The company is also compliant with the EU-US Privacy Shield Framework, which dictates how personal data can be transferred between the US and the EU, Riposati said. Dante stores customers' data in the cloud using Amazon Web Services but will delete customers' data upon request.
The company also seeks consent from its users for their data to be used for research purposes. In February, for example, Dante launched an epilepsy study, for which it will perform whole-genome sequencing on 1,000 individuals who have already been diagnosed with epilepsy, with the goal of identifying new drug targets. Epilepsy is a "complex, polygenic disease with different subtypes that have different treatments," Riposati said, and many patients are not treated effectively. As such, one goal is to identify new targets for anti-seizure drugs, he said.
He said the company is recruiting patients through social media and medical conferences focused on epilepsy. Thus far, around 150 people have enrolled and Riposati said he expects to have the sequencing completed for all 1,000 by the end of the year.