Separating the signal from the noise in metagenomic cell-free DNA sequencing

Burnham P, Gomez-Lopez N, Heyang M, Cheng AP, Lenz JS, Dadhania DM, Lee JR, Suthanthiran M, Romero R, De Vlaminck I.
Microbiome. 2020 Feb 11;8(1):18. doi: 10.1186/s40168-020-0793-4.
PMID: 32046792

Here, we report low biomass background correction (LBBC), a bioinformatics noise filtering tool informed by the uniformity of the coverage of microbial genomes and the batch variation in the absolute abundance of microbial cfDNA. We demonstrate that LBBC leads to a dramatic reduction in false positive rate while minimally affecting the true positive rate for a cfDNA test to screen for urinary tract infection. We next performed high-throughput sequencing of cfDNA in amniotic fluid collected from term uncomplicated pregnancies or those complicated with clinical chorioamnionitis with and without intra-amniotic infection.

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