Figure 1. Study overview.

Pediatric patients with acute respiratory failure requiring mechanical ventilation were clinically adjudicated into 4 LRTI status groups. The patients in the Definite and No Evidence groups, whose LRTI status was presumed to be known, were used to develop an integrated host/microbe mNGS classifier for LRTI and to evaluate its performance by cross-validation. The classifier was then applied to the patients in the Suspected and Indeterminate groups, whose LRTI status was considered uncertain. The integrated mNGS classifier takes into account a host probability of LRTI, derived from the host gene counts, and features of any viral or bacterial/fungal pathogens, derived from the nonhost (microbial) taxon counts.