Archives for November 2018

The Genetic and Molecular Epidemiology Laboratory (GMEL) at McMaster University is a premier genomics and proteomics facility offering a broad range of analytical services for academic and industry scientists. Established in 2009 by Guillaume Paré, MD, GMEL offers a broad array of cutting-edge “omics” platforms and technologies for high-throughput analyses of nucleic acids and protein biomarkers. Among the key services that GMEL offers are high-throughput DNA/RNA extraction, quantitation and quality assessment, microarrays (genotyping, gene expression, methylation), next-generation sequencing (exome, RNA, custom target, low-pass whole-genome), and multiplexed protein biomarker assays (>982 biomarkers simultaneously).

GMEL is affiliated with Hamilton Health Sciences’ Population Health Research Institute (PHRI), Thrombosis and Atherosclerosis Research Institute (TAaRI), and McMaster University. GMEL specializes in large-scale population genetic studies, and as such, is capable of handling project sizes ranging from single samples to >10,000 samples. With in-house Principal Investigators, project managers, statisticians, and bioinformaticians, GMEL provides support for experimental design, bioinformatics, statistical analyses, and the interpretation and reporting of results. GMEL is currently involved with multiple epidemiological studies and clinical trials, including CURE, ACTIVE, COMPASS, NAVIGATE ESUS, INTERSTROKE, ORIGIN, and PURE, among others.

While GMEL provides services in all areas of life sciences research, the laboratory has a particular focus on using the most cutting-edge genetic techniques to assess whether the promise of personalized medicine can be realized. The team explores the genetic risk of stroke, diabetes, obesity, and the response to some of the most widely prescribed drugs for those diseases.

Among GMEL’s key achievements was their description that clinical context is important when determining the effectiveness of clopidogrel treatment in patients with acute coronary syndromes or atrial fibrillation. Clopidogrel is used globally to reduce the risk of heart attack and stroke; however, studies by others showed that individuals carrying a CYP2C19 loss-of-function allele have an attenuated benefit from clopidogrel treatment, leading to an FDA black box warning. GMEL’s studies of acute coronary syndrome and atrial fibrillation added context to such findings and showed that the negative effects of loss-of-function alleles do not apply to all patient populations, and that the CYP2C19 gain-of-function allele may be equally or more important than the loss-of-function allele in specific populations. GMEL research also described a pharmacogenetic association between CES1 and the risk of bleed with the novel anticoagulant, dabigatran, and described an association between a COX-2 variant and its effect on aspirin. Research and collaborations from GMEL also identified genetic determinants of lipoprotein concentrations, glucose metabolism, homocysteine concentrations, as well as markers of inflammation, coronary artery disease, stroke, and atrial fibrillation.

Recent studies also resulted in the development of statistical methodologies and bioinformatics tools to identify gene-gene and gene-environment interactions, which have been adopted by multiple other research laboratories. GMEL developed a novel approach to test regional genetic associations, which has recently been expanded to include machine-learning approaches to determine polygenic risk scores. GMEL pioneered the use of Mendelian randomization (MR) to show that diabetes is causally involved in coronary heart disease, and that bile acid sequestrants reduce the risk of heart disease. The team also used MR to show that HER2 is a causal mediator of the protective effect of ACE inhibitors on kidney function.

GMEL has established a broad array of instrumentation for genomic and proteomic analyses. Among such instrumentation is the QIAsymphony instrumentation suite, BioAnalyzer, Fragment Analyzer, Gene Titan Array Scanner, Illumina iScan, Two Ion Torrent Series platforms for exome sequencing, BioNano Genomics Irys System, Thermofisher ViiA7 RT-PCR System, QuantStudio 3D Digital PCR System, Pyromark Q24 instrument, BioMark HD System, Bio-Plex Luminex Multiplex assays, Olink panel assays, and the SomaLogic SOMAscan technology, among others.

GMEL also has the necessary bioinformatics infrastructure (10 dedicated servers) to process large genomics projects at reasonable turnaround times. Among such infrastructure, GMEL uses Cisco Systems platforms, including a Quad Cisco UCSB-B200 bladed system, with combined Intel Xeon based 128 core CPU and 512 GB RAM, running within a VMware ESXi 5.5 environment. GMEL also uses a dedicated Cisco UCS C240 M4 rack application server, with Intel Xeon based 28 core CPU and 384 GB RAM, 3.2 TB Fusion-ion SX300 PCIe SSD and internal 8TB SAS 7.2K SFF HDD, running Linux based distribution.

From start to finish, GMEL provides a full-service analytical platform for researchers’ genomic and proteomic needs. Whether your project includes tens of samples or tens of thousands, GMEL is always willing to establish new collaborations and assist with your research. For more information about GMEL services, please contact Sue McMillan at 905-527-4322 ext. 40377, or smcmill@mcmaster.ca.