Interview with Andrew Magis of Arivale

Andrew Magis leads the Research Team at Arivale, responsible for developing and implementing cutting-edge approaches to large-scale analytics and systems modeling on longitudinal multi-omic data. Andrew was recruited from the Institute for Systems Biology (ISB) in Seattle, where he served as a key member of biotech pioneer Dr. Lee Hood’s pilot study team on the 2014 Pioneer 100 Wellness Project. The pilot focused on optimizing wellness through longitudinal data collection and analysis, generating tens of thousands of data points for each participant. As a result, ISB spun out Arivale, a company focused on combining personalized data and coaching to bring scientific wellness to consumers. Read his full bio.

Interview with Andrew Magis of Arivale

Q: Once sequencing has been validated as a clinical solution via trusted workflows, and coinciding with the technological developments driving costs lower, we can expect accelerated human genome profiling. How soon, do you think, will we see what kind of accelerated growth?

A: I think the acceleration has already begun. Large sequencing projects such as NHLBI Trans-omics for Precision Medicine (TOPMed) and NIH All of Us are sequencing 150,000 and 1 million individuals, respectively. This represents a growth of five to six orders of magnitude in the roughly 15 years since the first reference human genome was sequenced. Acceleration in the clinical space will depend on a number of factors: the cost of sequencing vs SNP genotyping, integration of non-Mendelian genetics into clinical practice, and FDA oversight.

Q: One of the main challenges associated with whole genome sequencing is the interpretation of the data. Do you expect whole genome profiling will stagnate if interpretation is lagging?

A: I do not think whole genome profiling will stagnate in the scientific community, as large sequencing studies are the mechanism through which we gain understanding and subsequent interpretation. Tremendous progress has been made in the past 15 years, and our understanding is accelerating, though there is certainly a long way to go. Whether or not the value of whole genome sequencing will accelerate into the consumer space in the short term is unclear. WGS is still much more expensive than SNP genotyping and the clinical value of one vs. the other is not yet distinct for the average individual.

Q: How will genome profiling change the standard-of-care in the near and/or far future?

A: There are several areas in which genome profiling could change the standard of care. Several recent studies have demonstrated the predictive ability of polygenic risk scores to stratify populations into low and high-risk cohorts across many diseases. These scores could be combined with current age-based screening (e.g. for breast cancer) to improve early detection and reduce screening costs. The efficacy of many drugs, including commonly-prescribed opioids and statins, depends on specific pharmacogenetic variants. Responses to these drugs may range from non-efficacy to toxicity, depending on the patient’s genetic profile.

Q: What are some of the main challenges we need to overcome to see widespread adoption of whole genome profiling across the clinic? How can the community come together to advance its adoption?

A: Widespread adoption of whole genome profiling in the clinic will require education and acceptance of clinicians, many of whom have not been trained to use such data in their practice. If genome sequencing is to replace other genotyping methods there needs to be an order of magnitude cost reduction, from $1000 to $100. Clinical applications of sequencing data today tend towards rare, highly penetrant pathogenic variants, whereas there are plausible applications in the areas of preventative medicine and population screening using more common variants.

Q: What solution is your organization/company providing to address what need in the genome profiling sector?

A: Arivale leverages genetic data (along with other omics data such as clinical tests) to improve the health of our members. Part of our approach involves building polygenic scores for clinical biomarkers (e.g. LDL cholesterol, BMI, HbA1c) and coaching at-risk individuals on strategies to reduce their risk of developing disease. We are researching the clinical outcomes of providing this genetic information to consumers in terms of response to lifestyle intervention. We are also exploring the impact of rare mutations in phenome-wide association studies. Leveraging our other omics data, we are furthering scientific discovery in disease pathophysiology, predictive disease biomarkers, and novel drug targets.

Q: Is there anything you would like to share with the PMWC audience?

A: Genome sequencing (and SNP genotyping) is made more valuable when paired with longitudinal, deep phenotyping derived from matched blood, stool, and saliva biosamples collected through the Arivale program. Arivale maintains an ever-growing database of thousands of deeply phenotyped individuals, including genomic, clinical, microbiome, metabolomic, proteomic, quantified self, health, and lifestyle data derived from these biosamples. Using these data, we can begin to understand the phenotypic effects of high polygenic risk for complex diseases such as type 2 diabetes, inflammatory bowel disease, and coronary artery disease. Furthermore, this longitudinal dataset is ideal for discovery/preclinical research, including phenome-wide association studies, biomarker discovery, and behavioral associations.