Data from: Metagenomic sequencing detects respiratory pathogens in hematopoietic cellular transplant patients

Rationale: Current microbiologic diagnostics often fail to identify the
etiology of lower respiratory tract infections (LRTI) in hematopoietic
cellular transplant recipients (HCT), which precludes the implementation
of targeted therapies. Objectives: To address the need for improved LRTI
diagnostics, we evaluated the utility of metagenomic next generation
sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial
pathogens in HCT patients with acute respiratory illnesses. Methods: We
enrolled 22 post-HCT adults ages 19-69 years with acute respiratory
illnesses who underwent BAL at the University of Michigan between January
2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and
simultaneously assess the host transcriptional response. Results were
compared against conventional microbiologic assays. Measurements and Main
Results: Standard of care clinical diagnostics identified microbes in
seven patients (32%), six of which were considered pathogens by treating
physicians, and all of which were detected by mNGS. Previously
unrecognized LRTI pathogens were also identified in six patients for whom
standard testing was negative (human coronavirus 229E, human rhinovirus A,
Corynebacterium propinquum and Streptococcus mitis); findings were
confirmed by independent PCR and 16S rRNA sequencing. Relative to patients
without infection, patients with infection had increased expression of
immunity related genes (p=0.022) and significantly lower diversity of
their respiratory microbiome (p=0.017).