A metagenomic DNA sequencing assay that is robust against environmental DNA contamination

Omary Mzava, Alexandre Pellan Cheng, Adrienne Chang, Sami Smalling, Liz-Audrey Kounatse Djomnang, Joan Sesing Lenz, Randy Longman, Amy Steadman, Luis G. Gómez-Escobar, Edward J. Schenck, Mirella Salvatore, Michael J. Satlin, Manikkam Suthanthiran, John R. Lee, Christopher E. Mason, Darshana Dadhania and Iwijn De Vlaminck ()
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Omary Mzava: Cornell University
Alexandre Pellan Cheng: Cornell University
Adrienne Chang: Cornell University
Sami Smalling: Cornell University
Liz-Audrey Kounatse Djomnang: Cornell University
Joan Sesing Lenz: Cornell University
Randy Longman: Weill Cornell Medicine, Jill Roberts Center for IBD
Amy Steadman: Global Health Labs
Luis G. Gómez-Escobar: Weill Cornell Medicine
Edward J. Schenck: Weill Cornell Medicine
Mirella Salvatore: Weill Cornell Medicine
Michael J. Satlin: Weill Cornell Medicine
Manikkam Suthanthiran: Weill Cornell Medicine
John R. Lee: Weill Cornell Medicine
Christopher E. Mason: Weill Cornell Medical College
Darshana Dadhania: Weill Cornell Medicine
Iwijn De Vlaminck: Cornell University

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract Metagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present Sample-Intrinsic microbial DNA Found by Tagging and sequencing (SIFT-seq) a metagenomic sequencing assay that is robust against environmental DNA contamination introduced during sample preparation. The core idea of SIFT-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can be recorded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied SIFT-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of sepsis and inflammatory bowel disease in blood.

Date: 2022
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DOI: 10.1038/s41467-022-31654-0

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