Benefits of pharmacogenomics
Pharmacogenomics, the understanding of how genes impact an individual's response to medications, plays an important role in certain prescribing situations through the identification of medication responders and non-responders. The utilization of pharmacogenomics assists in optimizing drug dose and avoiding adverse events, including toxicity and even death.
Pre-emptive pharmacogenomics microarray analysis
Using microarray analysis across predictive genomics applications, such as pre-emptive pharmacogenomics research areas, helps garner greater insights. This means researchers and scientists can be better informed and can confidently make decisions that support precision medicine efforts.
Significant progress has been made using genomics to help determine the safest, most effective course of treatments for individuals. As these programs scale and go mainstream, they are beginning to deliver on the promise of helping improve the health of communities and lowering healthcare costs.
As one example, the Teachers' Retirement System of Kentucky recently launched a pilot program that is already showing positive results from both an individual impact and cost-savings perspective. First, members who opt in receive a saliva collection kit which is analyzed using one of Thermo Fisher Scientific's pharmacogenomics technologies. Next, pharmacists review the participant's genetic results—along with health data such as drug, lifestyle, and food interactions—to customize a “Medication Action Plan” that members' physicians can access to determine which drugs should be changed to help increase safety and efficacy.
Thermo Fisher Scientific's predictive genomics solutions are part of an efficient workflow and can be scaled to your testing needs. We provide input on what is needed to customize your array, with hands-on support from start to finish so you can remain focused on shaping the future of healthcare.
Predictive genomics workflow
Population genotyping projects are enabling precision medicine decisions and helping improve health care outcomes. Many national governments and large organizations are investing in scaling up genotyping infrastructure to enable personalized solutions.
Our Axiom solution consists of a technology platform that includes assay biochemistry, automated and manual target preparation options, multiple array plate formats, and array processing on the GeneTitan Multi-Channel Instrument. This solution has applications in human genetics and microbiome research.
The Axiom assay and workflow begins with purified genomic DNA. The first part of the assay and workflow is Target Preparation, which includes whole genome amplification on day one, followed by DNA fragmentation and overnight precipitation on day two. On day three the DNA is resuspended and prepared for hybridization on the array. Finally, washing, ligation, and staining occurs on the GeneTitan instrument followed by scanning of the plate. Target preparation aims to prepare the genomic targets of interest so that they can be successfully attached, or “hybridized”, to the synthesized probes on the microarray for accurate results. Following hybridization, array processing involves washing non-specific binding DNA and scanning the microarray plate to detect the fluorescence signal from the genomic targets of interest. Finally, genotypes are reported using Axiom Analysis Suite software.
Let’s dive deeper into each step:
- Whole genome amplification: Since starting genomic DNA is limited and/or finite and typically original crude samples from which the DNA was extracted are also finite or not available, it is important to amplify the limited amount of starting genomic DNA so that there is plenty of DNA, including targets of interest, available to hybridize to the synthesized complimentary probes on the array plate. The Axiom assay requires 200 ng of total genomic DNA for whole genome amplification. This takes about 24 hours in a 37°C oven.
- Fragmentation: Cut the DNA into fragment sizes that are optimal for array hybridization. If DNA is too long, it may not bind. The Axiom assay utilizes enzymes that randomly fragment DNA into 25 to 125 base pair (bp) fragments.
- Precipitation: Purify and collect all the DNA fragments. Standard is overnight precipitation, but there is an option for a three-hour precipitation for a quicker turnaround time.
- Hybridization: DNA fragments pair to complimentary probe sequences on the array
- Wash, ligate, stain: The bound target is washed under stringent conditions to remove non-specific background to minimize background noise caused by random ligation events. Each polymorphic nucleotide is queried via a multi-color ligation event carried out on the array surface. After ligation, the arrays are stained and imaged on the Gene Titan MC Instrument.
- Scan: detection of fluorescence signal
- Data analysis: Primary and secondary analysis. Primary analysis is generation of the genotypes. Secondary analysis includes any analysis of the genotypes to understand groups of samples, genes, variants, etc.
Propel workflow: The above steps (excluding data analysis) have been optimized into a shortened two-day workflow, the Axiom Propel workflow, completing scanning of arrays by the end day 2. In addition, the Axiom Propel workflow has been optimized to include benchtop automation to increase the throughput, processing more plates in two days than the standard manual Axiom 2.0 assay.
For Research Use Only. Not for use in diagnostic procedures.