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High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation identification, variant calling, and phasing within each pharmacogene copy present in the sample. Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that uses combinatorial optimization for accurate star-allele calling across different sequencing technologies. Aldy 4 adds support for long reads and uses a novel phasing model and improved copy number and variant calling models. We compare Aldy 4 against the current state-of-the-art star-allele callers on a large and diverse set of samples and genes sequenced by various sequencing technologies, such as whole-genome and targeted Illumina sequencing, barcoded 10x Genomics, and Pacific Biosciences (PacBio) HiFi. We show that Aldy 4 is the most accurate star-allele caller with near-perfect accuracy in all evaluated contexts, and hope that Aldy remains an invaluable tool in the clinical toolbox even with the advent of long-read sequencing technologies.

As genomic technologies rapidly develop, polygenic scores (PGS) are entering into a growing conversation on how to improve precision in public health and prevent chronic disease. However, although the integration of PGS into public health clinical services raises potential benefits, it also introduces potential harms. In particular, there is a high level of uncertainty about how to incorporate PGS into clinical settings in a manner that is equitable, just, and aligned with the long-term goals of most healthcare systems to support person-centered and value-based care. This paper argues that any conversation about whether and how to design and implement PGS clinical services requires dynamic engagement with local communities, patients, and families. These parties often face the consequences, both positive and negative, of such uncertainties and should therefore drive clinical translation. As a collaborative effort between hospital stakeholders, community partners, and researchers, this paper describes a community-empowered co-design process for addressing uncertainty and making programmatic decisions about the implementation of PGS into clinical services. We provide a framework for others interested in designing clinical programs that are responsive to, and inclusive and respectful of, local communities.

Materials used for chemical looping can be exploited to process methane in a number of ways. Using the oxygen on the solid material leads to partial or total oxidation, whilst methane cracking to carbon on the depleted solid can produce hydrogen. Regeneration of the solid to remove the cracked carbon or restore the oxygen can produce CO, H2 or a combination if CO2 or H2O is used as the oxidant. The chemical looping material separates the conversion of methane from the addition of oxygen. Materials containing sorbents like CaO can interact with the CO2 produced to shift the equilibrium in desirable ways. These materials could be utilised to configure a cyclic process that is a linear combination of DRM, SMR, and cracking with combustive regeneration of the solid. Here, a material combining a catalyst (i.e. Ni), an oxygen carrier (i.e. Ca2Fe2O5) and CaO was investigated for converting methane to syngas or hydrogen-rich gas in a cyclic DRM process. In Stage 1, methane is converted to syngas or H2 in a fluidised bed of NiO/Ca2Fe2O5/CaO, where the solid is reduced/carbonated at, e.g., 700 °C; in Stage 2, the reduced/carbonated material is regenerated at 900 °C. The thermodynamic nature of the Ni-Ca-Fe-O system allows Ni to stay separate from Ca2Fe2O5, meaning that Ca inhibits the formation of any mixed oxide phase of Ni and Fe. A high rate of production of syngas or H2 (depending on different phases of Stage I) was found after the NiO/Ca2Fe2O5/CaO became activated. The activated NiO/Ca2Fe2O5/CaO gave high production of syngas or H2 for over 30 cycles without material deactivation. Carbon whiskers formed during CH4 processing, and such carbon solids did not cause deactivation.

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing, and to determine a minimal set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations on a minimal panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories in designing assays for PGx testing. When developing these recommendations, the Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations with regard to PGx testing. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document is focused on clinical CYP2D6 PGx testing that may be applied to all cytochrome P450 2D6–metabolized medications. These recommendations are not meant to be interpreted as prescriptive but to provide a reference guide for clinical laboratories that may be either implementing PGx testing or reviewing and updating their existing platform.

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This article provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This article focuses on clinical TPMT and NUDT15 PGx testing, which may be applied to all thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)-related medications. These recommendations are not to be interpreted as prescriptive, but to provide a reference guide.

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on‐clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole‐genome Infinium MEGA BeadChip array. An ancestry‐adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p

Oxyfuel combustion, as a carbon capture method, requires oxygen to be separated from nitrogen. Currently, cryogenic air separation is used for this purpose. An alternative is to use chemical looping, where an oxygen carrier is cycled between reducing and oxidising conditions. In this paper, the feasibility of using packed bed reactors in chemical looping air separation is studied. By introducing a compressor and turbine, oxidisers can be operated at an elevated pressure and the proposed scheme can be viewed as a power-station in its own right, in addition to its more recognised application of producing oxygen for a downstream oxy-fuel combustion. A single packed bed reactor is not able to meet the 0.30-0.35 oxygen molar fraction needed for an oxyfuel combustor. Therefore, multiple beds must be used in series or heat must be added radially along the bed length to increase the oxygen molar fraction in the bed.

Risk variants in the apolipoprotein L1 (APOL1 [OMIM 603743]) gene on chromosome 22 are common in individuals of West African ancestry and confer increased risk of kidney failure for people with African ancestry and hypertension. Whether disclosing APOL1 genetic testing results to patients of African ancestry and their clinicians affects blood pressure, kidney disease screening, or patient behaviors is unknown.To determine the effects of testing and disclosing APOL1 genetic results to patients of African ancestry with hypertension and their clinicians.This pragmatic randomized clinical trial randomly assigned 2050 adults of African ancestry with hypertension and without existing chronic kidney disease in 2 US health care systems from November 1, 2014, through November 28, 2016; the final date of follow-up was January 16, 2018. Patients were randomly assigned to undergo immediate (intervention) or delayed (waiting list control group) APOL1 testing in a 7:1 ratio. Statistical analysis was performed from May 1, 2018, to July 31, 2020.Patients randomly assigned to the intervention group received APOL1 genetic testing results from trained staff; their clinicians received results through clinical decision support in electronic health records. Waiting list control patients received the results after their 12-month follow-up visit.Coprimary outcomes were the change in 3-month systolic blood pressure and 12-month urine kidney disease screening comparing intervention patients with high-risk APOL1 genotypes and those with low-risk APOL1 genotypes. Secondary outcomes compared these outcomes between intervention group patients with high-risk APOL1 genotypes and controls. Exploratory analyses included psychobehavioral factors.Among 2050 randomly assigned patients (1360 women [66%]; mean [SD] age, 53 [10] years), the baseline mean (SD) systolic blood pressure was significantly higher in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes and controls (137 [21] vs 134 [19] vs 133 [19] mm Hg; P = .003 for high-risk vs low-risk APOL1 genotypes; P = .001 for high-risk APOL1 genotypes vs controls). At 3 months, the mean (SD) change in systolic blood pressure was significantly greater in patients with high-risk APOL1 genotypes vs those with low-risk APOL1 genotypes (6 [18] vs 3 [18] mm Hg; P = .004) and controls (6 [18] vs 3 [19] mm Hg; P = .01). At 12 months, there was a 12% increase in urine kidney disease testing among patients with high-risk APOL1 genotypes (from 39 of 234 [17%] to 68 of 234 [29%]) vs a 6% increase among those with low-risk APOL1 genotypes (from 278 of 1561 [18%] to 377 of 1561 [24%]; P = .10) and a 7% increase among controls (from 33 of 255 [13%] to 50 of 255 [20%]; P = .01). In response to testing, patients with high-risk APOL1 genotypes reported more changes in lifestyle (a subjective measure that included better dietary and exercise habits; 129 of 218 [59%] vs 547 of 1468 [37%]; P .001) and increased blood pressure medication use (21 of 218 [10%] vs 68 of 1468 [5%]; P = .005) vs those with low-risk APOL1 genotypes; 1631 of 1686 (97%) declared they would get tested again.In this randomized clinical trial, disclosing APOL1 genetic testing results to patients of African ancestry with hypertension and their clinicians was associated with a greater reduction in systolic blood pressure, increased kidney disease screening, and positive self-reported behavior changes in those with high-risk genotypes.ClinicalTrials.gov Identifier: NCT02234063.

To develop a novel pharmacogenetic genotyping panel, a multidisciplinary team evaluated available evidence and selected 29 genes implicated in interindividual drug response variability, including 130 sequence variants and additional copy number variants (CNVs). Of the 29 genes, 11 had guidelines published by the Clinical Pharmacogenetics Implementation Consortium. Targeted genotyping and CNV interrogation were accomplished by multiplex single‐base extension using the MassARRAY platform (Agena Biosciences) and multiplex ligation‐dependent probe amplification (MRC Holland), respectively. Analytical validation of the panel was accomplished by a strategic combination of > 500 independent tests performed on 170 unique reference material DNA samples, which included sequence variant and CNV accuracy, reproducibility, and specimen (blood, saliva, and buccal swab) controls. Among the accuracy controls were 32 samples from the 1000 Genomes Project that were selected based on their enrichment of sequence variants included in the pharmacogenetic panel (VarCover.org). Coupled with publicly available samples from the Genetic Testing Reference Materials Coordination Program (GeT‐RM), accuracy validation material was available for the majority (77%) of interrogated sequence variants (100% with average allele frequencies > 0.1%), as well as additional structural alleles with unique copy number signatures (e.g., CYP2D6*5, *13, *36, *68; CYP2B6*29; and CYP2C19*36). Accuracy and reproducibility for both genotyping and copy number were > 99.9%, indicating that the optimized panel platforms were precise and robust. Importantly, multi‐ethnic allele frequencies of the interrogated variants indicate that the vast majority of the general population carries at least one of these clinically relevant pharmacogenetic variants, supporting the implementation of this panel for pharmacogenetic research and/or clinical implementation programs.

The goal of the Association for Molecular Pathology (AMP) Clinical Practice Committee's AMP Pharmacogenomics (PGx) Working Group is to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered functional impact of the variants, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal is to promote standardization of PGx gene/allele testing across clinical laboratories. These recommendations are not to be interpreted as prescriptive but to provide a reference guide. Of note, a separate article with recommendations for CYP2C9 allele selection was previously developed by the PGx Working Group that can be applied broadly to CYP2C9-related medications. The warfarin allele recommendations in this report incorporate the previous CYP2C9 allele recommendations and additional genes and alleles that are specific to warfarin testing.

To facilitate reference-material selection for clinical genetic testing laboratories, we developed VarCover, open-source software hosted on GitHub, which accepts a file of variants and returns an approximately minimum set (min-set) of samples covering the targeted alleles. VarCover employs the SetCoverPy package, sample weights, and preselection of singleton-possessing samples to efficiently solve the min-set cover problem. As a test case, we attempted to find a min-set of reference samples from the 1000 Genomes Project to cover 237 variants considered putatively pathogenic (of which 12 were classified as pathogenic or likely pathogenic) in the original 56 medically actionable genes recommended by the American College of Medical Genetics and Genomics (ACMG). The number of samples, number of alleles, and processing time were measured in subsets of the 237 target alleles. VarCover identified 140 reference-material samples from the 1000 Genomes Project covering the 237 alleles in the 56 ACMG-recommended genes. Sample weights derived from the minor allele frequency spectrum increased the number of alleles in the solution set. Preselection of samples that possessed singleton target alleles reduced computational processing time when the target set size exceeded 100 alleles. VarCover provides a simple programmatic interface for identifying an approximately min-set of reference samples, thereby reducing clinical laboratory effort and molecular genetic test–validation costs.

Binary groups are a meaningful step up from non-associative rings and nearrings. It makes sense to study them in terms of their nearrings of zero-fixing polynomial maps. As this involves algebras of a more specialized nature these are looked into in sections three and four. One of the main theorems of this paper occurs in section five where it is shown that a binary group V is a P0(V) ring module if, and only if, it is a rather restricted form of non-associative ring. Properties of these non-associative rings (called terminal rings) are investigated in sections six and seven. The finite case is of special interest since here terminal rings of odd order really are quite restricted. Sections eight to thirteen are taken up with the study of terminal rings of order pn (p an odd prime and n ≥ 1 an integer ≤ 7).

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs, including nonsteroidal anti-inflammatory drugs, phenytoin, antidiabetic agents, and angiotensin receptor blockers. Variable CYP2C9 activity is of particular importance regarding efficacy and safety of warfarin and siponimod as indicated in their package inserts. This GeneFocus provides a comprehensive overview and summary of CYP2C9 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. Results: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy number variation and 9 common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. Conclusion: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

The goals of the Association for Molecular Pathology Pharmacogenomics (PGx) Working Group of the Association for Molecular Pathology Clinical Practice Committee are to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for CYP2C9 testing. The Working Group considered the functional impact of the variants, allele frequencies in different populations and ethnicities, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. Our goal is to promote standardization of testing PGx genes and alleles across clinical laboratories. These recommendations are not to be interpreted as restrictive but to provide a reference guide. The current document will focus on CYP2C9 testing that can be applied to all CYP2C9-related medications. A separate recommendation on warfarin PGx testing is being developed to include recommendations on CYP2C9 alleles and additional warfarin sensitivity–associated genes and alleles.

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

H2-rich gas production from CH4 at mild temperature (673 K), was achieved in a single step without introducing a separate oxygen stream. This was conducted in a plasma-assisted packed bed reactor in the presence of Ni-based catalysts doped on an active support, i.e. Fe2O3. Among the tested materials, NiO/Fe2O3 was found to be very promising and its excellent catalytic properties seemed to be induced by the presence of Fe2O3, which suppressed the formation of deposited carbon, and thus maintained the catalytic effect of metallic Ni (formed during NiO reduction by the CH4/Ar plasma). This work demonstrates the potential of plasma-assisted chemical looping partial oxidation for H2 production.

Aim: To comprehensively interrogate CYP2D6 by integrating genotyping, copy number analysis and novel strategies to identify CYP2D6*36 and characterize CYP2D6 duplications. Methods: Genotyping of 16 CYP2D6 alleles, multiplex ligation-dependent probe amplification (MLPA) and CYP2D6*36 and duplication allele-specific genotyping were performed on 427 African–American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals. Results: A novel PCR strategy determined that almost half of all CYP2D6*10 (100C>T) alleles are actually *36 (isolated or in tandem with *10) and all identified duplication alleles were characterized. Integrated results from all testing platforms enabled the refinement of genotype frequencies across all studied populations. Conclusion: The polymorphic CYP2D6 gene requires comprehensive interrogation to characterize allelic variation across ethnicities, which was enabled in this study by integrating multiplexed genotyping, MLPA copy number analysis, novel PCR strategies and duplication allele-specific genotyping.

The pyrolysis of wood in the presence of chemical looping agents including Fe2O3, mayenite-supported CuO and mayenite-supported Cu2O was studied from 773 to 1173 K. A continuous tar quantification system, based on a DBD reactor downstream of the fluidised bed, was developed to allow quantification of the tar formed. An oxygen-containing plasma was used to convert volatiles and tars to measurable carbon-containing species, mainly CO, CH4, and CO2. It was found that pyrolysis of the wood in alumina sand produced CH4, CO, CO2, tar and char as the main products. Tar cracking was observed above 1073 K, and this mainly generated CH4. Both Fe2O3 and mayenite-supported Cu-based oxides were effective for in situ combustion of the pyrolysis products, particularly tar, at temperatures exceeding 873 K. Mayenite-supported CuO showed the highest reactivity. The results showed the potential of using metal oxides for direct combustion of biomass, and particularly converting the tarry products during devolatisation. The better activity of mayenite-supported CuO compared to Fe2O3 and Cu2O in these experiments was mainly due to the ability of CuO to release gaseous oxygen at high temperatures.

Pharmacogenomics (PGx) can be seen as a model for biomedical studies: it includes all disease areas of interest and spans in vitro studies to clinical trials, while focusing on the relationships between genes and drugs and the resulting phenotypes. This review will examine different characteristics of PGx study publications and provide examples of excellence in framing PGx questions and reporting their resulting data in a way that maximizes the knowledge that can be built on them.

© 2018 Elsevier B.V. Three chars were gasified in CO2 in a fluidised bed of inert sand or Fe2O3 as an oxygen carrier (either derived from an ore or prepared in the laboratory). Rates of gasification were found to increase with temperature and the presence of active oxygen carriers. The observed change varied both with the chars’ and carriers’ reactivity. A numerical model was developed to simulate char gasification. It accounts for: intrinsic kinetics of gasification, intraparticle mass transfer in the char, external mass transfer in the particulate phase of the fluidised bed and CO combustion in the bed of Fe2O3. At 1223 K, CO was removed from the vicinity of the char on being oxidised by an oxygen carrier; this was accompanied by a simultaneous increase in CO2 concentration, reducing the limitation imposed by mass transfer. It was concluded that the acceleration of gasification by oxygen carriers is significant only if gasification is limited by mass transfer in the first place. In addition, an analytical solution has been proposed, to combine all the processes into one simplified expression for estimating the apparent gasification rate. The influence of the intraparticle resistance was introduced with the effectiveness factor; the gasification rate was linearized with a Taylor series; finally the processes in the particulate phase were described with an enhancement factor, based on the Hatta number. This simple analytical model allows one to predict the influence of an oxygen carrier on the gasification of char during chemical looping combustion. The proposed expression for the effective rate was used to construct a map of the enhancement expected for various kinetic characteristics of an oxygen carrier.

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the APOL1, NAT2, and YEATS4 genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus, 2. actionability, 3. context-sensitive triggers, 4. workflow integration, 5. feasibility, 6. interpretability, 7. portability, and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for APOL1, NAT2, and YEATS4 was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS.

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing, and to determine a minimal set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations on a minimal panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories in designing assays for PGx testing. When developing these recommendations, the Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations with regard to PGx testing. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document is focused on clinical CYP2D6 PGx testing that may be applied to all cytochrome P450 2D6–metabolized medications. These recommendations are not meant to be interpreted as prescriptive but to provide a reference guide for clinical laboratories that may be either implementing PGx testing or reviewing and updating their existing platform.

Since the term “pharmacogenetics” was first published in the late 1950s by Friedrich Vogel, the field has evolved into genome-wide association studies identifying novel variants associated with drug response phenotypes, international societies and consortia dedicated to pharmacogenomic research and clinical implementation, clinical practice guidelines, and the increasing availability of pharmacogenomic tests for healthcare providers in both hospital and primary care [...]