A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma.

Autor:	Müller J; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany.; Max Perutz Labs, Vienna Biocenter Campus, 1030 Vienna, Austria.; University of Vienna, Max Perutz Labs, Department of Structural and Computational Biology, Center of Integrative Bioinformatics Vienna, 1030 Vienna, Austria.; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria., Hartwig C; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany.; Institute for Interfacial Engineering and Plasma Technology, University of Stuttgart, 70569 Stuttgart, Germany., Sonntag M; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany.; Interfaculty Graduate School of Infection Biology and Microbiology, Eberhard Karls University Tübingen, 72074 Tübingen, Germany., Bitzer L; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany., Adelmann C; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany., Vainshtein Y; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany., Glanz K; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany., Decker SO; Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, 69120 Heidelberg, Germany., Brenner T; Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany., Weber GF; Department of Surgery, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, Germany., von Haeseler A; Center of Integrative Bioinformatics Vienna, Max Perutz Labs, University of Vienna and Medical University of Vienna, Vienna BioCenter, 1030 Vienna, Austria.; University of Vienna, Faculty of Computer Science Bioinformatics and Computational Biology, 1090 Vienna, Austria., Sohn K; Innovation Field In-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany; kai.sohn@igb.fraunhofer.de.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2024 Sep 20; Vol. 34 (8), pp. 1185-1195. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.1101/gr.279326.124
Abstrakt:	Here, we present a method for enrichment of double-stranded cfDNA with an average length of ∼40 bp from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we find significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA methylation, positively with H3K4me3 histone modifications and gene transcription. The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not yet been recognized. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with postoperative controls, we identify 136 and 241 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis, demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies. (© 2024 Müller et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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