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Inferring expressed genes by whole-genome sequencing of plasma DNA

The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing (WGS) of plasma DNA and identified two discrete regions at transcription start sites (TSS) where the nucleosome occupancy results in different read-depth coverage patterns in expressed and silent genes. By employing machine learning for gene classification we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells. In cancer patients with metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We could even determine the expressed isoform of genes with several TSSs as confirmed by RNA-Seq of the matching primary tumor. Our analyses provide functional information about the cells releasing their DNA into the circulation.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001002215 Illumina MiSeq NextSeq 550 108
EGAD00001002216 Ion Torrent Proton 2
EGAD00001002217 Illumina MiSeq 1
EGAD00001002254 Illumina MiSeq 3
Publications Citations
Inferring expressed genes by whole-genome sequencing of plasma DNA.
Nat Genet 48: 2016 1273-1278
Rapid diagnosis and comprehensive bacteria profiling of sepsis based on cell-free DNA.
J Transl Med 18: 2020 5