Inferring expressed genes by whole-genome sequencing of plasma DNA

Peter Ulz, Gerhard G Thallinger, Martina Auer, Ricarda Graf, Karl Kashofer, Stephan W Jahn, Luca Abete, Gunda Pristauz, Edgar Petru, Jochen B Geigl, Ellen Heitzer, Michael R Speicher

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

Abstract

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 of plasma DNA and identified two discrete regions at transcription start sites (TSSs) where nucleosome occupancy results in different read depth coverage patterns for 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 patients with cancer having metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We were able to determine the expressed isoform of genes with several TSSs, as confirmed by RNA-seq analysis of the matching primary tumor. Our analyses provide functional information about cells releasing their DNA into the circulation.

Originalspracheenglisch
Seiten (von - bis)1273-8
Seitenumfang6
FachzeitschriftNature genetics
Jahrgang48
Ausgabenummer10
DOIs
PublikationsstatusVeröffentlicht - Okt 2016

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DNA Sequence Analysis
Genome
DNA
Nucleosomes
Genes
Transcription Initiation Site
Neoplasm Genes
Neoplasms
Protein Isoforms
Medicine
Tissue Donors
RNA
Apoptosis

Schlagwörter

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    Ulz, P., Thallinger, G. G., Auer, M., Graf, R., Kashofer, K., Jahn, S. W., ... Speicher, M. R. (2016). Inferring expressed genes by whole-genome sequencing of plasma DNA. Nature genetics, 48(10), 1273-8. https://doi.org/10.1038/ng.3648

    Inferring expressed genes by whole-genome sequencing of plasma DNA. / Ulz, Peter; Thallinger, Gerhard G; Auer, Martina; Graf, Ricarda; Kashofer, Karl; Jahn, Stephan W; Abete, Luca; Pristauz, Gunda; Petru, Edgar; Geigl, Jochen B; Heitzer, Ellen; Speicher, Michael R.

    in: Nature genetics, Jahrgang 48, Nr. 10, 10.2016, S. 1273-8.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    Ulz, P, Thallinger, GG, Auer, M, Graf, R, Kashofer, K, Jahn, SW, Abete, L, Pristauz, G, Petru, E, Geigl, JB, Heitzer, E & Speicher, MR 2016, 'Inferring expressed genes by whole-genome sequencing of plasma DNA' Nature genetics, Jg. 48, Nr. 10, S. 1273-8. https://doi.org/10.1038/ng.3648
    Ulz, Peter ; Thallinger, Gerhard G ; Auer, Martina ; Graf, Ricarda ; Kashofer, Karl ; Jahn, Stephan W ; Abete, Luca ; Pristauz, Gunda ; Petru, Edgar ; Geigl, Jochen B ; Heitzer, Ellen ; Speicher, Michael R. / Inferring expressed genes by whole-genome sequencing of plasma DNA. in: Nature genetics. 2016 ; Jahrgang 48, Nr. 10. S. 1273-8.
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