Biocom LifeLines: Sapient Bioanalytics is Using a Multi-Omics Approach That Looks Beyond the Genome in Drug Discovery

Marie: Why look beyond the genome and the focus on proteomics, lipidomics and metabolomics?

Dr. Jain: Genomics was supposed to change drug development completely and transform this whole space of personalized medicine. But how much does our risk of developing a disease come from genetics versus other factors? It was expected to be quite high, but after a million genomes have been sequenced via the UK Biobank and other consortiums, the percentage of disease risk that is attributable to genetics is modest at less than 20% Now, there are rare populations at the extremes for which someone has a particular mutation or polygenic risk score for which their risk of disease goes up tremendously. But if you look across an entire population, genetics explain a minority fraction of disease. The idea that genomics alone would be able to be used for personalizing therapy, understanding targets, identifying who’s going to benefit from a particular drug, or just even for diagnostic purposes, doesn’t make sense.

The genome is largely static and unchanged from the moment of conception. There are diseases in which the genome does change—cancer being the prime example, as there are mutations that occur. What about other diseases for which the genome is not changing? Heart disease, GI illness, liver disease, immunology and inflammatory diseases, fibrotic diseases, neurodegenerative diseases and renal disease are all examples with limited genetic influence.

How do we begin to interrogate that? That was the basis of going beyond the genome with multi-omics technology to interrogate the dynamic markers that can read out a person’s health, future disease risk, what drugs they’re going to respond to: key information that we’re trying to capture as a way of complimenting their underlying genomic risk score.

Marie: What insights can you provide on how your work in the field stands out?

Dr. Jain: Mass spectrometry is our weapon of choice, as it’s an interesting multi-omics technology that has made several technical gains over the last 15 years. We can assay thousands of molecules in a given sample, whether they be metabolites, lipids or proteins. We can do this in a very robust and comprehensive fashion, and quite quickly.

We have deep expertise in this space. As part of my academic lab, I spent years taking apart mass spectrometry instruments and understanding how to make them faster, while measuring more molecules with greater breadth and depth, which is ultimately required for very high throughput discovery across large human populations.

Discovery can’t be done in tens to hundreds of people—it needs to be done in hundreds of thousands of people. We have some of the fastest, highest-capacity mass spectrometry workflows in the world. These allow us to take any biological specimen (such as a tumor or plasma sample, preclinical sample or cell culture sample) and assay thousands of metabolites, lipids, and proteins in those samples very quickly.