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Pharmacogenetic Implementation Studies-Lessons Learned From the PREPARE Study.

The Ubiquitous Pharmacogenomics consortium (www.upgx.eu) has recently completed and published the Preemptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study on the implementation of panel-based pharmacogenetic testing. …

Machine learning models for pharmacogenomic variant effect predictions - recent developments and future frontiers.

Pharmacogenomic variations in genes involved in drug disposition and in drug targets is a major determinant of inter-individual differences in drug response and toxicity. While the effects of common variants are well established, millions of rare …

Comprehensive analysis of multi-omics single-cell data using the single-cell analyst.

The rapid advancement of multi-omics single-cell technologies has significantly enhanced our ability to investigate complex biological systems at unprecedented resolution. However, many existing analysis tools are complex, requiring substantial …

The liver proteome of individuals with a natural UGT2B17 complete deficiency.

Glucuronidation is a crucial pathway for the metabolism and detoxification of drugs and endobiotics, and primarily occurs in the liver. UGT2B17 is one of the 22 glycosyltransferases (UGT) that catalyze this reaction. In a large proportion of the …

PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity …

Innovation in cancer pharmacotherapy through integrative consideration of germline and tumor genomes.

Precision cancer medicine is widely established, and numerous molecularly targeted drugs for various tumor entities are approved or are in development. Personalized pharmacotherapy in oncology has so far been based primarily on tumor characteristics, …

In silico and biological analyses of missense variants of the human biliary efflux transporter ABCC2: effects of novel rare missense variants.

The ATP-dependent biliary efflux transporter ABCC2, also known as multidrug resistance protein 2 (MRP2), is essential for the cellular disposition and detoxification of various xenobiotics including drugs as well as endogenous metabolites. Common …

Metabolic activation of WHO-congeners PCB28, 52, and 101 by human CYP2A6: evidence from in vitro and in vivo experiments.

Despite extensive research on the metabolism of polychlorinated biphenyls (PCBs), knowledge gaps persist regarding their isoform-specific biotransformation pathways. This study aimed to elucidate the role of different cytochrome P450 enzymes in PCB …

A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes.

Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability. This evaluation aims to describe the pharmacokinetics of noscapine using …

Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic …