Diagnosis by direct sequencing of pathogens. Diagnosis by direct sequencing of pathogens

Infections with microbes intractable to culture in vitro remain diagnostically challenging. Some pathogens require cellular culture, while eukaryotic organisms cannot be cultured. Diagnosis of these infections has depended historically on clinical and histological findings or targeted molecular detection. Here we describe as proof of principle the novel application of whole genome sequencing (WGS) directly from tissue to diagnose both mycobacterial infection (leprosy) and parasitic infection (coenurosis). Sequencing pathogen DNA direct from tissue samples provides a potentially portable solution to microbiological diagnosis of difficult pathogens that might be applied to improve diagnosis in diverse contexts, including in low resource settings.