NEW YORK (GenomeWeb) – Affymetrix launched its new transplant genotyping array this week, coinciding with two new papers from the International Genetics and Translational Research in Transplantation Network, with whom it designed the array.
The new product will help scientists uncover the mechanisms of transplant rejection, but could also be used in large cohort studies, pharmacogenomics, and immunological research, according to the firm. And research done using the array could eventually lead to better screening of potential donors to minimize risk of transplant rejection and the ability to predict successful transplant outcomes.
The Axiom Transplant Genotyping Array is the firm's first array focused on transplant genomics, Affymetrix Senior VP and General Manager of Genotyping Laurent Bellon told GenomeWeb. "It will be helpful in finding new associations in genomics in order to be able to predict and manage a transplant rejection," he said.
The array comprises around 780,000 markers, including 30,000 that may be related to transplant rejection, as well as markers related to immune system response, pharmacogenomics, and other diseases. It also includes around 350,000 SNPs to provide broad coverage of variants in different human populations, including African and Asian populations.
Affymetrix has also released a new software tool for typing human leukocyte antigen (HLA) based on genotype. HLA is currently the key biomarker for matching organ donors with transplant patients.
Since 1987, more than 575,000 solid organ transplants have been performed in the US alone, but 40 percent of patients see some degree of rejection in the first year. That number jumps to 60 percent over the course of the life of the transplant. HLA genetic incompatibility has long been correlated with transplant rejection, and new research now suggests that non-HLA differences between the organ donor and the transplant recipient are correlated with rejection as well.
Though designed for the International Genetics and Translational Research in Transplantation Network (iGenetrain), Affymetrix hopes the array can be of use to other researchers as well. The broad coverage will help the transplant array overlap with existing Axiom arrays used to genotype large cohorts, such as the UK Biobank, and the markers on it could aid research in fields that Affymetrix hasn't yet designed arrays for, such as immunology.
Collaboration with iGenetrain
The iGenetrain consortium includes key institutions in the US and abroad, including the University of Pennsylvania, Massachusetts General Hospital, University Medical Center Utrecht in the Netherlands, Children's Hospital of Philadelphia, and University College London, among others. Bellon identified Penn researcher Brendan Keating as Affymetrix's main collaborator on designing the array.
The iGenetrain consortium published two papers this month on the array design and application, one in Genome Medicine and one in Transplantation.
"Just like with every other consortium, it was central to get the objectives very clear," Bellon said. "These arrays have a particular pan-population element to it, so they can be a resource to the greater community, not only in North America but also in Asia and Europe. As a result, there was lot of focus associated with providing high genomic coverage in many of the European, African, and Asian populations.
The broad coverage of different populations was key for transplant research, where differences in variants are at the crux of the problem of rejection. "Thanks to the 1,000 Genomes Project, we know that several populations with different variants in the populations don't match each other as far as the [HLA] variants go," Marijo Gallina, Affymetrix marketing manager for the Axiom Transplant Genotyping Array, told GenomeWeb. "Variants that occur in one population may not occur in other, and [certain variants] may be more important in one than in others. It's very important to look at variants important to the population that you're screening."
Many of those areas of broad coverage came as modules from other Axiom arrays. "Within the iGenetrain array, a lot of the genomic coverage [markers] in different populations are fundamentally modules leveraged from other arrays," Bellon said. Markers for genomic areas of interest to transplant researchers, like pharmacogenomics, were also leveraged from existing arrays.
Being able to modularize those markers could be a boon to future meta-analyses in many fields, Bellon said.
"We see a lot of interest in this particular leverage because it makes meta-analysis of various cohorts that much easier," he said. "In the era where major cohorts are getting to public release stage — I'm referring to the UK Biobank cohort, which is starting to be publically available — people can leverage some of the information of these large cohorts to supplement their studies. Having some commonalities in the particular markers help that integration."
Bellon said that the project drew on many of the resources Affymetrix can provide to its customers, including the development of advance bioinformatics. Along with the transplant array, Affymetrix has launched HLA analysis software that features automated HLA typing from any genotyping data from any source.
"It's well suited to Axiom, of course, but we can use our algorithm and software for any type of genotype provided to us," Gallina, the array product manager, said. For the software, Affymetrix collaborated with Gil McVean from Oxford University, licensing an algorithm for HLA typing from SNP genotypes. "We integrated that into a graphic user interface that is very easy to use. There's only one step to get to HLA typing from your genotyping data; you just press a button, import your genotyping data and you get HLA typing from that," she said.
HLA typing wasn't easily obtainable before, Gallina said. Previous algorithms required a reference panel for the human population that corresponded to the person the sample came from and needed to do separate runs for each population.
Affymetrix has designed the software so that it can put all the reference populations in one panel and the software matches them to the patient samples. "You don't have to have any separate processing for different populations," she said. "It can handle any population all at once. African populations, Caucasian populations, no matter what population you're looking at, you can use multi-population input and the algorithm will cover them."
The software is optimized for high-throughput genotyping and provides 4-digit HLA typing, taking about 4 hours per 96-sample plate, Gallina said. The tool is free for Affymetrix customers.
Beyond the field of transplant genomics, the new array could be used broadly, from immunological research to GWAS studies, the Affymetrix officials said.
Gallina suggested that the pharmacogenomic panel, now updated in the Axiom database, could be relevant for many clinical trials or early in drug discovery. Pharmacogenomic markers are important to transplant research because the patients are put on immunosuppressant drugs, she said, but the array contains many markers that would be relevant elsewhere.
Because of the importance of the immune system in transplant medicine, and conversely the importance of HLA to the immune system, the array will be useful to immunology research, for which Affymetrix said it has not yet created an array.
"HLA is the most associated region in the human genome related to diseases," Gallina said. "Anyone doing a GWAS study would absolutely be interested in the HLA region because it's highly the most polymorphic and most associated [with disease] in the genome." Additionally, some of the markers are involved in inflammatory processes. "All of those markers are relevant to anyone doing immunological research," she said.