Orthrus: an AI-powered, cloud-ready, and open-source hybrid approach for metaproteomics

While metaproteomics provides invaluable insight into microbial communities and functions, significant bioinformatics challenges persist due to data complexity and the limitations of database searching. We introduce Orthrus, a hybrid approach combining transformer-based de novo sequencing (Casanovo) and database searching with rescoring (Sage+Mokapot). Benchmarking against PEAKS(R)11, MaxQuant, and MetaNovo, Orthrus demonstrates high peptide outputs, taxonomic diversity, and proteome coverage. Orthrus is Python-based and accessible to all via Google Colaboratory.