NEW YORK – MedGenome has partnered with Thermo Fisher Scientific to genotype hundreds of thousands of South Asian cohorts using a custom genotyping array. The personalized medicine company hopes to use the new array to inform new consumer and clinical tests, while also making it available to others for research.
"The limitation in South Asia has been that there are no genotyping array platforms that were optimized for large-scale genotyping," said MedGenome CSO Andy Peterson. "That seemed to be something we needed to fix, to serve as a foundation for all of our efforts."
MedGenome maintains its headquarters in Foster City, California, where it runs a next-generation sequencing facility. It also has offices in Bangalore, India, and in Singapore and employs 450 people worldwide. Supported by recent financing efforts — it closed a Series C round worth $40 million last year — the company has rolled out medical, cancer, reproductive, and infectious disease testing in the Indian market. Through its Bangalore office, it has also partnered with 550 hospitals and has access to data from tens of thousands of patients representing more than 4,500 population groups across India.
It is this data, in part, that has been used to build the new chip, which is called the South Asian Research Genotyping Array by MedGenome (SARGAM). Thermo Fisher has been working with MedGenome to design the array for manufacture on its Applied Biosystems Axiom platform. Thermo Fisher gained the Axiom platform through its 2016 acquisition of Affymetrix. With that deal came extensive experience in designing population-specific arrays for large-scale genotyping projects, such as the UK Biobank, for which Affymetrix and partners had designed a chip that was used to genotype 500,000 people.
Peterson said that MedGenome considered working with both Illumina and Thermo Fisher on the project, but opted for the latter given its experience in similar projects.
"Fundamentally, it came down to the fact that the business model Thermo Fisher is pursuing now is to design custom arrays," said Peterson. "They see population-optimized arrays as being something important to how they see the array business continuing to develop," he said. "Obviously, that resonated very much for our needs, in terms of [working in] an area of the world where there really aren't arrays specifically designed."
While MedGenome and Thermo Fisher announced the array last month, the chip is not commercially available, and is still being optimized for use. This involves running assays on MedGenome's full marker set across two arrays, the performance of which will then be used to inform the design of a final screening chip.
By the middle of 2020, the partners hope to start production of SARGAM. Patterson said MedGenome plans to genotype about 25,000 individuals first on the array, then scale up to genotyping about 200,000 more.
Thermo Fisher and MedGenome are also in discussions about making the array design available to others.
"We think there has been a gap in technologies, a limitation in terms of the relatively few genetic studies that have been done in South Asians," he said. "Most genetic studies to date have been done on Europeans," Peterson added. "We wanted to make sure this tool is available for other people, so we can rectify this deficiency."
The content for the array has been sourced from around India. For years, MedGenome has been involved in a separate project to characterize genetic diversity across Asia called GenomeAsia 100K, where partners have aimed to sequence 100,000 genomes of individuals around the region. Through this work, MedGenome has been able to get a better sense of South Asian diversity.
"A defining characteristic of South Asia is the diversity of different populations compared to Europe or to East Asia," said Peterson. He noted that India's population has three major subpopulations, one centered in the northwest, near Pakistan, a second in the south, and a third in the northeast where there is an East Asian genetic influence. To build the SARGAM chip, MedGenome drew on genetic markers from these three corners of the subcontinent.
The main thrust is of course to develop better tests for these populations. By genotyping samples on the array, MedGenome hopes to obtain insights that will enable it to draw up new designs for consumer-facing tests, like ancestry, or for pharmacogenomics assays geared toward Indian populations.
"It hasn't been possible to design a product effectively for consumers in the sense that the available arrays are suboptimal for South Asians," said Peterson. "For MedGenome, it's clearly an opportunity to use the array to give good information back to consumers, such as an ancestry information," he said. Another angle is genetic risk prediction, Peterson noted.
In terms of the large-scale genotyping planned on the array, Peterson said there are "two large buckets" of samples that MedGenome wants to look at. One is hospital-based disease cohorts, meaning patient samples with quality clinical and longitudinal information. Another would be local biorepositories, through which the firm can access cohorts that are not defined by disease state and are more representative of the general population.
"We are also working on opportunities that might be presented by the use of the array for genetic risk prediction," noted Peterson. He said that MedGenome might recruit some cohorts through offering them genetic risk predictions for certain conditions. "We see opportunities to create new study cohorts," said Peterson. "Our focus now is building those sample sets that will capitalize most effectively on the use of the array."
MedGenome is now seeking new investments to drive these efforts, he added.
Thermo Fisher's view
For Thermo Fisher, the work with MedGenome is seen as a natural extension of its previous work with a variety of partners including the UK Biobank, the FinnGen project in Finland, and the Million Veteran Program in the US. Other similar partners have included Taiwan Biobank and Precision Medicine, the Tohuku MegaBiobank in Japan, and the Korea Biobank.
Shantanu Kaushikkar, director of genotyping microarrays for Thermo Fisher Scientific, said the population-optimized Axiom arrays have "formed the backbone of research" on polygenic risk scores, and have been used to identify disease variants and to improve health outcomes for individuals at risk for disease.
In particular, he cited the UK Biobank work as preparing Thermo Fisher for other such partnerships. After the UK Biobank project was completed in 2014, Affymetrix, and subsequently Thermo Fisher, incorporated new approaches into its array design process and bioinformatics analysis software, he noted. It included the ability to address applications such as pharmacogenomics, rare variant typing, and designing for complex regions within the genome and copy number variation for whole-genome and targeted regions.
For instance, he said, the Axiom platform supports the ability to interrogate rare and common pharmacogenomic variants, "some of which are within pseudogenes and difficult to interrogate on other platforms." The company has also gained experience in designing "imputation-aware custom arrays" using its bioinformatics pipeline. This involves taking sequencing data and selecting variants that will provide the best coverage and accuracy for the populations of interest.
"This is akin to using artificial intelligence for array designs," said Kaushikkar.
Additionally, Thermo Fisher is also offering MedGenome the unique capability to screen the content from sequencing data to be able to design multiple arrays for different applications. Such a strategy has been used by several of the firm's customers such as the Korea Biobank and the Tohoku Megabiobank, both of which designed population-specific arrays, he said.
Thermo Fisher also made the third generation of the Japonica NEO array, which the Tohuku Megabiobank has used to genotype cohorts, available as a catalog array in Japan. While it is unclear if and when the SARGAM chip could be made similarly available, Kaushikkar confirmed it would be made available to partners of MedGenome if so desired.
"In support of MedGenome's study of South Asian populations, we will work with MedGenome to offer their custom array to their partners and customers," said Kaushikkar. "We do not intend to offer the array to anyone without MedGenome's involvement or approval," he added.
"Perhaps in the future Medgenome and Thermo Fisher may decide that it is of mutual benefit to have the SARGAM array become available as a catalog array similar to the Japonica NEO array," Kaushikkar noted. However, there are no plans to make SARGAM available as a catalog array in the coming year, he said.