Lusamaki, E. K. | Search bioRxiv

bioRxiv2025

Human outbreak detection and best practice MPXV analysis and interpretation with squirrel

High numbers of reported mpox cases and recent identification of multiple sustained human outbreaks of MPXV have highlighted the need for robust, best-practice genomic surveillance tools. In light of the SARS-CoV-2 pandemic, many labs across the globe developed the capacity to do virus genome sequencing, however MPXV presents additional analytical challenges due to its large genome size, tracts of low-complexity or repeat regions, genetically distinct clades, and the need to perform bespoke APOBEC3-mutation reconstruction. We present squirrel (Some Quick Reconstruction to Resolve Evolutionary Links), an open source bioinformatic tool that can perform clade-aware alignment, mutation quality assessment, phylogenetic inference and automated APOBEC3-mutation classification on branches of the phylogeny. Squirrel can be run on the command line or launched through the EPI2ME GUI through the squirrel-nf workflow, enabling robust analysis without need for the command line. With the interactive output report produced and publication-ready APOBEC3-reconstruction visualisation, squirrel enables researchers to distinguish between zoonotic and sustained human outbreaks and help accurately inform public health responses.

evolutionary biology↗

bioRxiv2025

Identifying genomic surveillance gaps in Africa for the global public health response to West Nile Virus

BackgroundWest Nile Virus (WNV) is a zoonotic flavivirus of significant One Health relevance and is classified as a priority pathogen with a high-risk of causing public health emergencies of global concern. WNV is endemic to Africa; however, the availability of genomic sequences from the continent remains limited. MethodsWe review the extent of polymerase chain reaction testing and genomic sequencing of WNV conducted across Africa. Using phylogeographic methods, we map the spatiotemporal spread of the virus across the continent and globally. FindingsOur study shows that WNV has been detected in 39 African countries (including Comoros, Seychelles, and Mauritius), the Canary Islands, and Reunion Island. Publications including molecular data originate from 24 countries; however, genomic sequences are publicly available for only 16 countries. We identify regions with detected viral circulation but lacking molecular surveillance. Further, we list such regions that overlap with Key Biodiversity Areas (sites harbouring significant bird diversity) as they may host high viral circulation, and high human population density that may be susceptible to spillover. InterpretationWe recognise significant knowledge gaps on the true disease burden, molecular epidemiology, and distribution of WNV in Africa. Addressing these gaps requires an integrated One Health surveillance approach which is challenging to establish. We propose three key surveillance needs as potential starting points to improve our understanding of the virus in Africa to strengthen the global public health response to this disease. FundingRockefeller Foundation, the National Institute of Health USA, Institute of Human Virology Nigeria, Global Health EDCTP3 Joint Undertaking, the Health Emergency Preparedness and Response Umbrella Program, managed by the World Bank Group, the Medical Research Foundation, and the Wellcome Trust.

molecular biology↗