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Genesis ~ PGxOneTM Plus

A comprehensive pharmacogenomics test that predicts effective treatment and dosage.

Genesis ~ PGxOneTM Plus Pharmacogenomics Test

Genesis PGxOne PlusGenesis ~ 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.

Disease diagnosisClinically actionable interpretation drug selection and dosage

Designed for a Lifetime

Lifetime portability for patientsGenesis 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


Comprehensive Coverage

Genesis ~ PGxOneTM Plus assays 25 well-established pharmacogenomics genes in a single test:

Cutting-edge Technology

Next generation sequencing technology delivers superior coverage of metabolizer phenotypes and variants compared to microarray assays. Utilizing this advanced technology, Genesis ~ PGxOneTM Plus detects:

Advanced Reporting

Proprietary bioinformatics methodologies for data analysis and interpretation:


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


1 DNA Extraction

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.

2 Library Preparation

Genesis ~ PGxOneTM Plus amplicon libraries are prepared from the isolated DNA.

3 Next Generation Sequencing

Next Generation Sequencing on the Ion PGM™ with 1×200 bp single-read SR configuration garners > 100x coverage (average) of target regions.

4 Analysis, Interpretation, & Reporting

The Genesis ~ PGxOneTM Plus report delivers extensive genetic information, patient genotype and phenotypes, and clinical recommendations.


Genesis ~ PGxOneTM Plus Performance Metrics

Performance metricsUsing 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.

Genesis PGxOne Plus reportsThe 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

Gene

Applicable Therapeutic Areas

CYP1A2 Psychiatry
CYP2C19 Cardiology; Gastroenterology; Infectious Diseases; Neurology; Psychiatry; Rheumatology
CYP2C9 Cardiology; Endocrinology; Rheumatology
CYP2D6 Cardiology; Dentistry; Neurology; Oncology; Pain Management; Psychiatry; Urology
DPYD Oncology
F5 Hematology; OB/GYN
G6PD Endocrinology; Infectious Diseases;Oncology; Rheumatology
HLA-B Infectious Diseases; Neurology; Rheumatology
IFNL3 Infectious Diseases
SLCO1B1 Cardiology
TPMT Oncology; Rheumatology
UGT1A1 Oncology
VKORC1 Cardiology
ATM Endocrinology
CYP2A6 Neurology
CYP3A4 Cardiology; Immunology; Oncology; Pain Management; Psychiatry; Urology
CYP3A5 Cardiology; Immunology
CYP4F2 Cardiology
DDRGK1 Infectious Diseases
F2 Endocrinology; Oncology
ITPA Rheumatology
LDLR Cardiology
MTHFR Oncology
NAT2 Infectious Diseases
STK11 Endocrinology

 

References

  1. 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.
  2. Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. The New England journal of medicine. 2011 Mar 24;364(12):1144-53.
  3. 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.
  4. 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.
  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.
  6. 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.
  7. 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.
  8. Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. British journal of pharmacology. 2009 Oct;158(3):693-705.