Nature Biotechnology | Trade Secrets

Unlocking the Molecular Diagnostic Interpretation Bottleneck

As noted in the news feature Direct-to-consumer genomics reinvents itself, 23andMe has filed to secure 510(k) clearance for some of its genetic tests, which poses the question of whether a foot in the door at the FDA will increase demand and re-energize the direct to consumer (DTC) genomics market?

FDA approval is undoubtedly an important step, but it will not address the most fundamental bottleneck to growth of the DTC market. The far more fundamental problem to the evolution, growth and value of genomic testing, whether DTC or through a physician-driven model, is the inability to scale the interpretation of these tests and the need to improve, by several orders of magnitude, the speed and quality of interpretation and variant classification.

For decades, clinicians have been running tests of a single gene or a small panel of genes for tightly defined phenotypes. These tests have emphasized clinical validation or confirmation of a clinical hypothesis, and the tests have generally been limited to genetic variation associated with broadly accepted clinical guidelines and benefits. Even so, a small- to medium-sized lab employs five to 10 medical geneticists and pathologists to interpret, score and report on these tests.

As the industry moves to testing with larger gene panels, exomes and whole genomes, and as we target these tests to more complex and multiple phenotypes, the time and complexity of interpreting these tests will grow exponentially.  Add to this the desire to run millions of tests per year, and the interpretation becomes intractable with current solutions. No clinical geneticist can handle the enormous complexity, and no testing lab can hire enough medical geneticists to scale and address the need with currently available solutions.

The bottom line is that for the DTC and molecular diagnostic market to grow much beyond its current state and realize its full potential, the industry needs to develop fundamentally new content and software solutions that deliver many orders of magnitude improvements in the time, quality and cost to interpret and classify genetic variation.

At Ingenuity, we think in terms of comprehensive curation of all known human phenotype variations from peer-reviewed literature and computationally tractable models of biology that allow us to more fully understand the impact of genetic variation on the biological system.

Easy-to-use software that enables clinical geneticists or pathologists to quickly and with high confidence produce test reports with clinical relevance and impact is the solution. Until innovative companies and the scientific community solve this problem, no amount of FDA clarification, sequencing technology improvement or reduction in the cost per test will materially alter the market dynamics. By every estimate this is a daunting task, but science had the ingenuity to drop the price of sequencing faster than Moore’s law over the past 10 years, and now together we need to focus our attention on unlocking the full market and clinical potential by addressing the interpretation bottleneck before it becomes a showstopper.

Jake Leschly, CEO, Ingenuity Systems



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    Andrew Marshall said:

    One question that arises from this, especially for a blog with international readership, is the extent to which companies providing genome analysis solution are (and will be) likely located in the US and Western Europe or elsewhere. Currently most of the genome analysis companies that receive attention (not only Ingenuity but also SV Biosystems, CLC Bio, Golden Helix, Parket, Omixon, Genformatic, Seven Bridges, Knome, Cypher Genomics, JSI Medical Systems, Personalis, Genomatix, Omicia and Station X to name a few) seem to be from there. It would be interesting to know what is going on outside of these countries. Also are non-Western companies focusing on research applications rather than more difficult clinical interpretation applications given the margins and likely dissemination of sequencing in those countries? It is interesting that BGI just bought Complete Genomics (many have said for its CLIA platform and foothold in US market). But what about genome analysis solutions?

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    Patrick Merel said:

    Thank you for this interesting post and comment. When it comes to the international development of Bio-IT solution in that space, don’t be confused with Europe contribution. You should say UK contribution only instead. With France and Germany being the most restrictive countries in regards of access to genome information, this industry is facing not only technical difficulties but also bioethics in a large portion of European countries. Yes, this is stupid, but this is still reality.

    I can share here part of my story. I’m the founder of Portable Genomics based in La Jolla, CA. We are developing a mobile platform for genome visualization and use in personalized medicine applications. This platform is targeted at healthcare professionals AND consumers. It is a consumer-based interface that will make it simple for professionals to use the data in their practice, and that will allow consumers to start being educated about genome data while participating to genome annotation through social networking and serious gaming utilities.

    I had to bring this entrepreneurial project from France to the US, because France would fined €15,000 patients who want to access their own genome data through DTC-Genomics companies. France is a nightmare for genome-IT entrepreneurs. They just recommended me to move away. So here I am, and I can tell, US is THE major driver for genome analysis from a sequencing technology and testing perspective as well as for bio-IT solutions.

    As a molecular biologist and molecular diagnostic practitioner I have seen the increasing amount of information that is provided to clinicians nowadays. And we even do not talk about exome or genome sequencing here. And they mostly get results on paper or through incomprehensible software that still require a PhD in bio-IT. That is not gonna work. Even with the most appropriated interpretation algorithm. Same with genome data as soon as they will disseminate in the public.

    There is here a real bottleneck that Portable Genomics will try to solve.