A comprehensive pharmacogenomics test that predicts effective treatment and dosage.
Genesis ~ PGxOneTM Plus Pharmacogenomics Test
Genesis ~ PGxOneTM Plus is a clinical pharmacogenomics test that predicts how patients will respond to drug therapy based on their individual genetic makeup. Differences between individuals can affect drug absorption, metabolism, or activity. Therefore, while one treatment regimen may work well for one individual, the same regimen may cause adverse effects for other individuals.1, 2 Genesis ~ PGxOneTM Plus comprehensively screens 25 well-established pharmacogenomic genes in a single, cost-effective test that provides medically actionable and clinically relevant data, thus allowing physicians to make effective treatment decisions.
Designed for a Lifetime
Genesis Genome and it’s alliance in USA, Admera Health performed extensive literature and database reviews to identify expertly curated pharmacogenomic biomarkers that reliably inform treatment decisions. Leveraging next generation sequencing technology, Genesis ~ PGxOneTM Plus assays these pharmacogenomic biomarkers. The resulting comprehensive gene panel delivers medically actionable data and interpretation with lifetime portability for patients.
Proactive Testing for Improved Quality of Life
Adverse drug effects have a serious impact on health outcomes. The overall incidence of adverse effects in the United States patient population is estimated to be 6.7%, and the associated costs of these adverse effects are estimated to exceed $100 billion.3, 4 Proactive pharmacogenomic testing can make a significant difference in reducing the incidence and cost of adverse drug effects. Since patients’ individual genetic makeup does not change over time, proactive pharmacogenomic testing using Genesis ~ PGxOneTM Plus reduces the need for multiple or repeat testing, further reducing costs associated with adverse events. Proactive testing also reduces the burden associated with reactive testing following drug exposure, enabling increased peace of mind for both patients and physicians.5 For example, research suggests that hospitalization rates for patients receiving warfarin treatment would be decreased by 31% if the patients underwent pharmacogenomic testing.6
The Genesis ~ PGxOneTM Plus Advantage
Genesis ~ PGxOneTM Plus assays 25 well-established pharmacogenomics genes in a single test:
- 196 variants influence several therapeutic areas
- Cost-effective testing, with additional cost benefits for patients with co-morbidities
- Recognized by the FDA and other international regulatory bodies as key pharmacogenomic genes
Next generation sequencing technology delivers superior coverage of metabolizer phenotypes and variants compared to microarray assays. Utilizing this advanced technology, Genesis ~ PGxOneTM Plus detects:
- Nucleotide substitutions
- Insertions and deletions
- Copy number variations (CNVs)
Proprietary bioinformatics methodologies for data analysis and interpretation:
- Intuitive, medically actionable report
- Clear, concise, and clinically relevant recommendations inform effective treatment
- Portable report with lifetime utility reduces the need for future testing
Detection of CNVs in CYP2D6
Genesis ~ PGxOneTM Plus is capable of detecting and providing information about copy number variations (CNVs) in the CYP2D6 gene. CNVs refer to DNA fragments larger than 1 Kb with a variable number of copies compared to a reference genome; CNVs typically result from a deletion or duplication event. CNVs are a major source of genetic variation within an individual’s genome. Importantly, CYP2D6 is responsible for metabolizing approximately 25% of drugs on the market, and CYP2D6 CNVs impact the metabolism of 50% of these drugs.7 Genesis ~ PGxOneTM Plus utilizes a proprietary bioinformatics algorithm to detect and provide CYP2D6 CNV information.
Genesis ~ PGxOneTM Plus Test Design
A total of 76 amplicons ranging in size from 135-391 bp were designed with the variant-of-interest in the center, ±50 bp. Primers are pooled and used to prepare sequencing libraries directly from genomic DNA (gDNA). After conducting quality control (QC), libraries are sequenced on the Ion PGM™. The resulting data undergoes analysis with a proprietary bioinformatics workflow to detect substitutions, Indels, and CNVs. After analysis, the data enters an interpretation pipeline designed to establish links between variants and relevant phenotypes. Lastly, an intuitive report is generated for the physician.
Genesis ~ PGxOneTM Plus Workflow
gDNA is extracted from buccal swabs , and is followed by rigorous quality control (QC) to verify the quality of the DNA. If gDNA samples are submitted, they are subject to (QC) to assess and verify the quality of the DNA.
Genesis ~ PGxOneTM Plus amplicon libraries are prepared from the isolated DNA.
Next Generation Sequencing on the Ion PGM™ with 1×200 bp single-read SR configuration garners > 100x coverage (average) of target regions.
The Genesis ~ PGxOneTM Plus report delivers extensive genetic information, patient genotype and phenotypes, and clinical recommendations.
Genesis ~ PGxOneTM Plus Performance Metrics
Using a common set of reference samples, Genesis ~ PGxOneTM Plus data (variant detection) was validated by direct comparison to data generated by Sanger sequencing. Genesis ~ PGxOneTM Plus displayed 100% sensitivity (true positive detection rate) and 100% specificity (true negative detection rate). Genesis ~ PGxOneTM Plus accuracy was determined to be >99.99%.
Genesis ~ PGxOneTM Plus: Drug Metabolizer Phenotypes
Our USA Alliance, Admera Health, stratifies clinical recommendations into the following categories:
Cytochrome P450 CYP enzyme polymorphisms are a determining factor in a patient’s ability to respond to different drugs. CYP enzymes are found within the endoplasmic reticulum of liver cells where they metabolize drugs and allow elimination of waste through urine.3 The polymorphisms of transporter enzymes, such as the OATP family of transporters, have also been linked to differences in the pharmacokinetics of drug absorption. For example, a single nucleotide polymorphism in the SLCO1B1 gene, which encodes the OATP1B1 enzyme, leads to impaired absorption of statins.8 For CYP and transporter enzymes, the Genesis ~ PGxOneTM Plus test results classify a patient’s drug response into one of the following categories: ultra-rapid metabolizer; poor metabolizer; intermediate metabolizer; or normal metabolizer.7
Admera Health, USA, analyzes Genesis ~ PGxOneTM Plus next generation sequencing data via proprietary bioinformatics algorithms, and then translates the results into recommended clinical actions based on specific FDA-approved drugs with pharmacogenomic indications.
To illustrate how Genesis ~ PGxOneTM Plus results translate into clinical recommendations for doxepin and atomoxetine (examples of drugs affected by metabolizer enzyme phenotypes) and simvastatin (an example of drugs affected by transporter enzyme phenotypes):
For therapies affected by other enzyme types for example the drug transporter enzyme Simvastatin
The Genesis ~ PGxOneTM Plus Report
Genesis ~ PGxOneTM Plus results are provided in a clear, concise, and easy to understand document.
The first page of the Genesis ~ PGxOneTM Plus report highlights drug recommendations specific to a patient’s diagnosis or disease. Recommendations are divided into four quadrants, each representing one of four categories: consider alternative; dose recommendation; normal response expected; and proceed with caution. Drugs specific to a patient’s diagnosis appear within each quadrant based upon the test results.
The second page of the Genesis ~ PGxOneTM Plus report includes expanded details about the clinical recommendations, including genes tested, patient genotype and resulting phenotype, and recommendations for the associated drugs.
Subsequent sections provide extensive genetic information, supporting life-long patient treatment.
Genesis ~ PGxOneTM Plus Applicable Therapeutic Areas
Applicable Therapeutic Areas
|CYP2C19||Cardiology; Gastroenterology; Infectious Diseases; Neurology; Psychiatry; Rheumatology|
|CYP2C9||Cardiology; Endocrinology; Rheumatology|
|CYP2D6||Cardiology; Dentistry; Neurology; Oncology; Pain Management; Psychiatry; Urology|
|G6PD||Endocrinology; Infectious Diseases;Oncology; Rheumatology|
|HLA-B||Infectious Diseases; Neurology; Rheumatology|
|CYP3A4||Cardiology; Immunology; Oncology; Pain Management; Psychiatry; Urology|
- Kitzmiller JP, Groen DK, Phelps MA, Sadee W. Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Cleveland Clinic journal of medicine. 2011 Apr;78(4):243-57.
- Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. The New England journal of medicine. 2011 Mar 24;364(12):1144-53.
- Samer CF, Lorenzini KI, Rollason V, Daali Y, Desmeules JA. Applications of CYP450 testing in the clinical setting. Molecular diagnosis & therapy. 2013 Jun;17(3):165-84.
- Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA : the journal of the American Medical Association. 1998 Apr 15;279(15):1200-5.
- Van Driest SL, Shi Y, Bowton EA, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2014 Apr;95(4):423-31.
- Epstein RS, Moyer TP, Aubert RE, et al. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). Journal of the American College of Cardiology. 2010 Jun 22;55(25):2804-12.
- Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacology & therapeutics. 2007 Dec;116(3):496-526.
- Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. British journal of pharmacology. 2009 Oct;158(3):693-705.