Detection of cryptogenic malignancies from metagenomic whole genome sequencing of body fluids.

摘要: BACKGROUND Metagenomic next-generation sequencing (mNGS) of body fluids is an emerging approach to identify occult pathogens in undiagnosed patients. We hypothesized that metagenomic testing can be simultaneously used detect malignant neoplasms addition infectious pathogens. METHODS From two independent studies (n = 205), we human data generated from a pipeline screen for malignancies by copy number variation (CNV) detection. In the first case-control study, analyzed fluid samples 124) patients with clinical diagnosis either malignancy (positive cases, n 65) or infection (negative controls, 59). second verification cohort, series consecutive cases 81) sent cytology workup included positives 32), negatives 18), unclear gold standard 31). RESULTS The overall CNV test sensitivity across all was 87% (55 63) confirmed conventional and/or flow cytometry and 68% (23 34) who were ultimately diagnosed cancer but negative testing. Specificity 100% (95% CI 95-100%) no false detected 77 controls. one example, patient hospitalized unknown pulmonary illness had non-diagnostic lung biopsies, while CNVs implicating detectable bronchoalveolar fluid. CONCLUSIONS undetected through This study illustrates potential utility single uncover cause acute illnesses due using same specimen.