Ameen, A. | Search bioRxiv

bioRxiv2026

Quantitative horizon scanning identifies high-priority wood-boring beetle pests for regulatory review in Canada

Invasive wood-boring beetles are a significant threat to forests, imposing high economic and environmental costs. With their high global biodiversity, it is difficult to assess all wood-boring beetles potential to invade a particular region. Horizon scanning can create short-lists of high priority pests for risk assessment by National Plant Protection Organizations; however, it is often resource-intensive, creating potential blind spots due to resource constraints. Here, we use a multi-layered horizon scan, including self-organizing maps and climate suitability modelling combined with rapid risk assessment, to produce a short-list of wood-boring beetles for regulatory review in Canada. This method relies on open-source data and could be applicable to any country. From an initial list of 10,824 species with available georeferenced observations, our method yielded a short-list of 24 species. The method led to the regulation of two additional wood-boring beetles in Canada, demonstrating its real-world applicability in accelerating the regulation of quarantine pests. Several already-regulated species were also identified, suggesting consistency with existing risk identification and assessment procedures. The limitations on the method are the availability of biologically meaningful species occurrence data, relevance of climate norms for species establishment, and availability of data for rapid risk assessment.

ecology↗

bioRxiv2025

Framework for combined functional and computational assessment of variant pathogenicity in the sodium leak channel NALCN

The sodium leak channel nonselective (NALCN) is the pore-forming channel component of the NALCN channelosome. This protein complex generates a depolarizing sodium leak in various tissues and contributes to respiratory and circadian rhythms, locomotion, and sleep. De novo and inherited variants of NALCN can lead to severe developmental syndromes called contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) and infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1), respectively. Although variants of uncertain significance (VUS) or presumed pathogenic variants have been studied in heterologous expression systems before, there is no generally accepted framework on how to assess or predict variant pathogenicity. We set out use the functional and computational characterization of 19 VUS detected in CLIFAHDD and IHPRF1 patients to establish a robust analysis to classify suspected disease-causing variants. Specifically, we employ a combination of multiple parameters derived from two-electrode voltage-clamp electrophysiology recordings and predicted protein stability and conservation scores. We show that this approach is capable of distinguishing benign common variants from both gain- and loss-of-function (GoF/LoF) variants. Additionally, our work provides mechanistic insight into the molecular mechanism underlying specific variants and provides insight into the unusual propensity of NALCN missense variants to result in GoF phenotypes. We anticipate that this experimental and computational framework will aid assessment of variant pathogenicity of NALCN and other components of the channelosome in the future.

genetics↗