Thursday, 05. November 2026, 10.00 a.m.
– to be announced

ResistanceProfiler: Standardizing Viral Resistance Genotyping

Dr. Jonas Fuchs
(Junior Research Group Leader, Clinical Virus Genomics, Institute of Virology, University Medical Centre Freiburg, Germany)

Antiviral resistance can compromise treatment efficacy due to prolonged viral replication, and limit therapeutic options. However, there is no generally accepted standard for interpreting viral genomic variation in relation to drug susceptibility. Established resources, such as the Stanford HIV Drug Resistance Database, provide pathogen-specific interpretations, but approaches differ across pathogens. Differences in variant nomenclature, evidence representation, and support for next-generation sequencing data complicate integration into bioinformatics workflows and adaptation to novel therapeutics or custom databases.

A common computational framework should standardize database representation, data processing, and reporting while preserving established pathogen- and database-specific interpretation logic. We developed ResistanceProfiler (ResPro), an open-source, viral pathogen-agnostic framework that separates sequence analysis from curated resistance knowledge. ResPro builds SQLite databases from reference sequences and tabular resistance rules linking mutations to phenotypic classifications, IC50 values, or other measures of drug susceptibility. It accepts FASTA and VCF inputs and maps provided sequences to the best-matching reference feature in a strand- and intron-aware manner. The analysis engine annotates coding consequences, including substitutions, insertions, deletions, and frameshifts. Beside effects of single substitutions, ResPro can also evaluate the combined amino-acid consequences of multiple variants within the same codon using phasing information or, when unavailable, bounds on likely variant co-occurrence derived from allele frequencies using Fréchet inequalities. It also supports complex resistance rules that combine mutations using Boolean operators. Results are reported in standardized HTML, PDF, TSV, and JSON formats.

We ported five independently curated resources: the HSV-1/HSV-2 database compiled by Jaki et al. (2025), the pan-herpesvirus resource herpesDRG, the human cytomegalovirus database ChARMD, the Stanford HIV Drug Resistance Database, and the WHO influenza rulesets. Database conversion workflows support updates, and compatible releases can be retrieved through the command-line interface. Custom databases are supported as well, allowing laboratories to apply the same analysis framework to internally curated resistance knowledge. ResPro is the first common computational framework for genotypic resistance interpretation across viral pathogens but retains database-specific evidence and interpretation logic. The software is available as a command-line application through Bioconda and as a web interface hosted by the University Medical Center Freiburg. Its source code is available at https://github.com/the-foxlab/ResistanceProfiler.
See also:
https://www.linkedin.com/posts/jonas-fuchs-16bba9133_after-over-6-months-of-work-respro-is-share-7507829548311425025-hRf7/