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bioRxiv · 10.1101/2025.09.19.677253

Targeted ortholog search in unannotated genome assemblies with fDOG-Assembly

Muelbaier, H.·Arthen, F.·Tran, V.·Schaefer, I.·Balint, M.·Ebersberger, I.
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Abstract

Whole genome shotgun sequencing and assembly is routine. However, identifying protein-coding genes in newly assembled genomes remains complex, time-consuming, and labour-intensive. Therefore, most eukaryotic genome assemblies in public databases lack gene annotations reducing their value for evolutionary and functional genomics. Here, we present fDOG-Assembly, a novel tool for targeted, feature architecture-aware ortholog searches directly in unannotated genome assemblies. Benchmarking shows that fDOG-Assembly performs similarly to BUSCO and Compleasm in ortholog identification while offering the advantage of not being restricted to universal single-copy genes. Applied to identify orthologs of 5,000 human genes in rat and Nematostella vectensis, fDOG-Assembly approaches the performance of traditional ortholog search tools that rely on pre-annotated proteomes. Importantly, it can recover orthologs missed by conventional methods because of incomplete gene annotations, helping to fill gaps in phylogenetic profiles. As a case study, we screened 176 soil invertebrate genome assemblies for genes involved in antibacterial compound production. We found that orthologs of {beta}-lactam biosynthesis genes are widespread in springtails, with individual species possessing nearly complete cephamycin biosynthetic gene sets, suggesting they may represent previously unrecognized natural producers of {beta}-lactam antibiotics. Overall, fDOG-Assembly is a powerful resource for orthology-based analyses of the rapidly growing collection of unannotated genome assemblies.

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Muelbaier, H., Arthen, F., Tran, V., Schaefer, I., Balint, M., Ebersberger, I.. 2025-09-21. Targeted ortholog search in unannotated genome assemblies with fDOG-Assembly. https://doi.org/10.1101/2025.09.19.677253

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