PAnno: A pharmacogenomics annotation tool for clinical genomic testing

Abstract

Introduction: Next-generation sequencing (NGS) technologies have been widely used in clinical genomic testing for drug response phenotypes. However, the inherent limitations of short reads make accurate inference of diplotypes still challenging, which may reduce the effectiveness of genotype-guided drug therapy.Methods: An automated Pharmacogenomics Annotation tool (PAnno) was implemented, which reports prescribing recommendations and phenotypes by parsing the germline variant call format (VCF) file from NGS and the population to which the individual belongs.Results: A ranking model dedicated to inferring diplotypes, developed based on the allele (haplotype) definition and population allele frequency, was introduced in PAnno. The predictive performance was validated in comparison with four similar tools using the consensus diplotype data of the Genetic Testing Reference Materials Coordination Program (GeT-RM) as ground truth. An annotation method was proposed to summarize prescribing recommendations and classify drugs into avoid use, use with caution, and routine use, following the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC), etc. It further predicts phenotypes of specific drugs in terms of toxicity, dosage, efficacy, and metabolism by integrating the high-confidence clinical annotations in the Pharmacogenomics Knowledgebase (PharmGKB). PAnno is available at https://github.com/PreMedKB/PAnno.Discussion: PAnno provides an end-to-end clinical pharmacogenomics decision support solution by resolving, annotating, and reporting germline variants.

Targeted haplotyping in pharmacogenomics using Oxford Nanopore Technologies’ adaptive sampling

“…For NA19785, the improved calls for CYP2B6 and SLCOB1 are concordant with the results of Liu Y. et al (Liu et al, 2023). For CYP2E1, the Agena assay did not examine *4 nor *5, while the variants were manually validated to be present in IGV (Supplementary Figure S6).…”

“…Affymetrix found *5 but called the other allele as *27 as it incorrectly assumed the presence of the rs36079186 variant. The *1/ *61 call compared to the *2/*62 call of the GeT-RM NGS panel for CYP2C9 was also reported by Liu Y. et al (Liu et al, 2023). For CYP3A4, *36 was not assessed in the GeT-RM studies.…”

A comprehensive personal omics clinical interpreter based on genomic and transcriptomic profiles

“…The FUSCC dataset can be split into six categories of test files: somatic variants (279 patients), germline variants (279 patients), CNV (401 patients), TMB (57 patients), and gene expression (88 patients). Haplotype/diplotype information and corresponding drug responses were obtained based on germline variants using the PAnno tool [25] in the drug response module. Therefore, the inclusion of these datasets ensures comprehensive validation of the performance of POI.…”

“…Hence, the analysis of germline variation data, particularly gene polymorphisms associated with drug metabolism and drug targets, enables the prediction of patient sensitivity to chemotherapeutic drugs to improve the precision medicine. To accomplish this, our module incorporates our previously developed pharmacogenomics annotation tool PAnno [25] into the POI framework. Through the analysis of germline variants, we infer the genotypes/diplotypes of genes related to chemotherapeutic drugs, enabling the prediction of patient phenotypes about toxicity, dosage, efficacy, and drug metabolism.…”