Pharmacogenetics and Drug Metabolism

ExposoGraph: An Interactive Platform for Carcinogen Bioactivation and Detoxification Pathway Visualization

ExposoGraph is an interactive knowledge-graph platform that visualizes carcinogen metabolism and DNA damage pathways, integrating data from multiple sources to support gene-environment interaction studies.

Reversible in vivo regulation of drug metabolizing enzyme CYP1A2 activity through a dTAG knock-in strategy

This paper introduces a method to reversibly regulate CYP1A2 enzyme activity in mice using a dTAG knock-in strategy, demonstrating its utility in drug metabolism studies.

Organophosphorus pesticide and nerve agent surrogate metabolism by human CYP3A4

This study evaluates CYP3A4's metabolism of organophosphorus compounds and finds it preferentially metabolizes thions over oxons, with some compounds inhibiting CYP3A4 activity.

Massively parallel reporter assays for CYP3A4 enhancer variants alongside their native promoter

The paper uses a modified MPRA to assess CYP3A4 enhancer variants with their native promoter, identifying variants with significant regulatory impact on drug response and cancer severity.

Adherence to International Pharmacogenomic Recommendations in Paediatric Cancer Care: A Cohort Analysis Embedded Within the MARVEL-PIC Randomised Trial

This paper analyzes adherence to pharmacogenomic recommendations in paediatric cancer care, finding low explicit adherence rates despite available recommendations.

PHARMWATCH: A Multilayer Pharmacogenomics Safety System for Accurate Star Allele Interpretation

PHARMWATCH improves pharmacogenomics safety by identifying genomic alterations that affect star allele accuracy, enabling more reliable drug dosage recommendations.

A New Fluorogenic Substrate for CYP1A2 and Its Application in Studying the Effects of Alcohol Exposure on Liver Drug Metabolism

This paper introduces a new fluorogenic substrate, MONA, for CYP1A2 and uses it to study how chronic alcohol exposure affects CYP1A2 activity in human liver microsomes.

Pharmacogenomic Variants in the Russian Population: A Retrospective Analysis of 6102 Exomes

The paper analyzes pharmacogenomic variants in 6,102 Russian exomes, identifying key drug metabolism and toxicity-related variants and highlighting limitations of WES for non-coding variant imputation.

A novel pharmacogenetic testing panel for CYP2C19 genetic polymorphisms

This paper introduces a cost-effective multiplex genotyping method for CYP2C19 variants using FAS-PCR, achieving accurate genotype calls comparable to pyrosequencing.

Evolution of the Cytochrome P450 Family 4 (CYP4) Subfamilies in Birds

This study examines CYP4 evolution in birds using 363 genomes to explore how gene variation relates to ecological traits and metabolic strategies, identifying positive selection in substrate recognition sites.

Pharmacogenomic variant profiling in 14,490 Koreans using a population-specific genotyping array

This study profiles pharmacogenomic variants in 14,490 Koreans using a population-specific array, showing high concordance and highlighting ancestry-specific pharmacogenomic diversity.

Complete pharmacogenomic profile from exome sequencing

This paper presents a method to derive a complete pharmacogenomic profile from exome sequencing data, validated against multiple reference assays.

Linking interpersonal differences in gut microbiota composition and drug biotransformation activity

The paper examines how gut microbiota composition affects drug metabolism by analyzing 271 drugs across 89 microbial communities and develops models to predict microbiota-mediated drug metabolism.

Near, far, wherever you are: Phenotype-related variation in pharmacogenomic effect sizes across the psychiatric drug literature.

This study quantifies pharmacogenomic effect sizes for psychiatric drugs, finding larger effects for proximal outcomes like bioavailability than distal outcomes like efficacy and toxicity.

Investigating CYP2C9*3 Polymorphisms in Patients with Neuropsychological Disorders through Pharmacogenomics Testing

This study examines CYP2C9*3 polymorphisms in patients with neuropsychological disorders using pharmacogenomics testing and finds a higher frequency of *1/*1 genotype compared to *1/*3.

A Sulfotransferase from a Gut Microbe Acts on Diverse Phenolic Sulfate Compounds, Including Acetaminophen Sulfate

This study identifies a gut microbial sulfotransferase that sulfonates diverse phenolic compounds, including acetaminophen sulfate, suggesting microbial enzymes may contribute to host detoxification.

Human CYP2C9 metabolism of organophosphorus pesticides and nerve agent surrogates

This study investigates how CYP2C9 metabolizes organophosphorus pesticides and nerve agents, finding that it preferentially metabolizes thions over oxons and that binding energy correlates with metabolism and inhibition.

Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility

The paper identifies common loss-of-function genes and develops a method to integrate them into cell-based models to assess population variability in chemical susceptibility.

Gut bacteria generate prodrugs in situ increasing systemic drug exposure

The paper identifies gut bacteria that convert drugs into prodrugs, increasing systemic drug exposure and altering pharmacokinetics.

Resolving the CES1 Genomic Locus with Cas9-Directed Targeted Long-Read Sequencing for Precision Pharmacogenomics

This study uses long-read sequencing to resolve the complex CES1 genomic locus, identifying new haplotypes and structural variants, and highlighting issues with short-read sequencing artifacts.

Development of a New Approach Method to Monitor and Modify Caffeine Metabolism Correlated to CYP1A2 Expression

The paper develops an in vitro platform to monitor and modify caffeine metabolism linked to CYP1A2 expression using paraxanthine and qPCR.

VSPGx: A High-Accuracy Pharmacogenomics Interpretation Software Solution with Automated CPIC Guideline Integration

VSPGx is a pharmacogenomics software that accurately identifies diplotypes and annotates them with CPIC guidelines, outperforming existing tools in synthetic and clinical benchmarks.

No Evidence of Genotype-Treatment Interactions between Endocrine Therapies and Adverse Drug Effects in Women with Breast Cancer: Findings from the UK Biobank

This study examines genotype-treatment interactions in endocrine therapy for breast cancer using UK Biobank data and finds no significant associations between genomic variants and adverse drug effects.

deCYPher: Star Allele-Resolution Computational Framework of Pharmacogenes for Haplotype-Resolved Long-Read Assemblies

deCYPher is a computational framework for pharmacogene analysis using haplotype-resolved assemblies, demonstrating high accuracy in resolving complex gene structures and identifying allele variations.

Reconstitution of human cytochrome P450 activity using a Leishmania cell-free protein expression system

This study demonstrates the use of a Leishmania cell-free system to express and assay human P450 enzymes 3A4 and 2D6, showing distinct reductase preferences and drug interaction consistency.

MICRORNAS AS REGULATORS OF DRUG METABOLISM AND TRANSPORT IN PREGNANT AND LACTATING WOMEN

This study identifies differentially expressed miRNAs regulating drug metabolizing enzymes and transporters during pregnancy and lactation, revealing their association with sex hormone levels and placental function.

Clinical Impact of Pharmacogenetic Risk Variants in a Large Chinese Cohort

The paper evaluates the clinical impact of pharmacogenetic risk variants in a large Han Chinese cohort, finding that while most carry risk variants, the excess risk of adverse events is small and most patients do not experience adverse outcomes.

VarDrug: A Machine Learning Approach for Variant-Drug Interaction, Application to Drugs for Psychiatric Disorders

VarDrug predicts variant-drug interactions using machine learning on PharmGKB data, achieving 90% F1 score for psychiatric disorder applications.

Human xenobiotic metabolism proteins have full-length and split homologs in the gut microbiome

The paper identifies full-length and split homologs of human xenobiotic metabolism proteins in the gut microbiome, revealing their roles in drug metabolism and highlighting potential implications for microbial contributions to xenobiotic processing.

Genes Encoding Xenobiotic Detoxification Proteins evolve by gene death, duplication and positive selection

This study examines the evolution of drug-metabolizing genes across vertebrates, showing gene loss, duplication, and positive selection contribute to interspecies variability in drug metabolism.