Project description:Pathogen sequencing from biopsy tissue for the diagnosis of infectious diseases not identified through conventional microbiological techniques
Project description:Critical protein therapeutics, such as antibodies and nanobodies, are often not encoded in reference genomes, limiting their accurate characterization via standard proteomics. Current methods rely on indirect inference, fragmented outputs, and labor-intensive workflows, which hinder functional insights and routine application. Here, we present a generalizable, end-to-end workflow for direct protein sequencing, combining streamlined sample preparation, AI-driven de novo peptide sequencing, and tailored assembly to reconstruct contiguous protein sequences. A novel composite scoring framework prioritizes longer assemblies and coverage, enhancing accuracy and reducing ambiguity. Validation across diverse protein modalities demonstrates its utility and ability to robustly reconstruct functionally critical regions essential for optimizing therapeutic efficacy, stability, and immunogenicity. This workflow advances precision proteomics with promising applications in therapeutic discovery, immune profiling, and protein engineering.
Project description:Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts.