Package: panno
PAnno: A Pharmacogenomics Annotation Tool for Clinical Genomic TestingPAnno reportsprescribing recommendationsanddrug response phenotypesby parsing the germline variant call format (VCF) file from NGS and the population to which the individual belongs.InstallationPrerequisite: To ensure smooth installation and usage,Python >= 3.7(#1 and #3 below), orMiniconda/Anaconda(#2 below) are required.You can install PAnno fromPyPIusing pip as follows:pipinstallpanno==0.3.1Alternatively, you can create a environment usingConda.condacreate-nPAnnopanno=0.3.1-clyaqing-cconda-forge-cbioconda
condaactivatePAnnoIf you would like the development version instead, the command is:pipinstall--upgrade--force-reinstallgit+https://github.com/PreMedKB/PAnno.git# Or download first and install latergitclonehttps://github.com/PreMedKB/PAnno.git;pipinstallPAnnoUsageOnce installed, you can use PAnno by navigating to your VCF file and entering the corresponding three-letter abbreviation of the population:panno-ssample_id-igermline_vcf-ppopulation-ooutdirRequired arguments-s,--sample_idTEXTSampleIDthatwillbedisplayedinthePAnnoreport.

-i,--germline_vcfTEXTUnannotatedVCFfile,preferablygermlinevariant.

-p,--population[AAC|AME|EAS|EUR|LAT|NEA|OCE|SAS|SSA]Thethree-letterabbreviationforbiogeographicgroups:AAC(AfricanAmerican/Afro-Caribbean),AME(American),EAS(EastAsian),EUR(European),LAT(Latino),NEA(NearEastern),OCE(Oceanian),SAS(Central/SouthAsian),SSA(Sub-SaharanAfrican).

-o,--outdirTEXTCreatereportinthespecifiedoutputpath.Input data1. Germline VCF filePAnno directly uses the NGS-derived germline VCF file as input and assumes it has undergone quality control. Therefore, if the VCF file is of poor quality, inaccurate diplotypes and inappropriate clinical recommendations may be reported.PAnno requires the VCF file aligned to the GRCh38 reference genome given the increasing generality and the built-in diplotype definition dependency version.2. PopulationThere are nine biogeographic groups supported by PAnno. Please use thethree-letter abbreviationas input. This is to prevent errors caused by special symbols such as spaces.AAC(African American/Afro-Caribbean),AME(American),EAS(East Asian),EUR(European),LAT(Latino),NEA(Near Eastern),OCE(Oceanian),SAS(Central/South Asian),SSA(Sub-Saharan African).More information is available athttps://www.pharmgkb.org/page/biogeographicalGroups.Output dataThe report is created in${sample_id}.htmlat theoutdirby default.For more detailed instructions, runpanno -h.ExamplesThedemodirectory contains the VCF files and PAnno reports of four Coriell samples: NA10859 (European), NA19147 (African American/Afro-Caribbean), NA19785 (Latino), and HG00436 (East Asian).In addition, we analyzed the germline variants of 88 samples which have been characterized in the GeT-RM PGx studies.The VCF files are available athttps://github.com/PreMedKB/PAnno-analysis/tree/main/vcf.The PAnno reports are available athttps://github.com/PreMedKB/PAnno-analysis/tree/main/report.Here is a snapshot from the PAnno report:Core ComponentsA ranking model dedicated to inferring diplotypes, developed based on theallele (haplotype) definitionandpopulation 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 prescriptions and classify drugs intoavoid use,use with caution, androutine 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).