Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis

Elisabeth Ullrich; Petra Heidinger; Jung Soh; Laura Villanova; Stefan Grabuschnig; Thorsten Bachler; Elisabeth Hirschböck; Sara Sánchez-Heredero; Barry Ford; Maria Sensen; Ingund Rosales Rodriguez; Daniel Schwendenwein; Peter Neumeister; Christoph J Zurl; Robert Krause; Johannes Lorenz Khol; Christoph W Sensen

doi:10.1016/j.jbiotec.2020.01.013

Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis

Elisabeth Ullrich, Petra Heidinger, Jung Soh, Laura Villanova, Stefan Grabuschnig, Thorsten Bachler, Elisabeth Hirschböck, Sara Sánchez-Heredero, Barry Ford, Maria Sensen, Ingund Rosales Rodriguez, Daniel Schwendenwein, Peter Neumeister, Christoph J Zurl, Robert Krause, Johannes Lorenz Khol, Christoph W Sensen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

We have identified 24 molecular markers, based on circulating nucleic acids (CNA) originating from the human genome, which in combination can be used in a quantitative real-time PCR (qPCR) assay to identify the presence of human sepsis, starting two to three days before the first clinical signs develop and including patients who meet the SEPSIS-3 criteria. The accuracy was more than 87% inside of the same patient cohort for which the markers were developed and up to 81% in blind studies of patient cohorts which were not included in the marker development. As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis. Our assay directly uses an aliquot of cell-free blood as the substrate for the PCR reaction, thus allowing to obtain the diagnostic results in three to four hours after the collection of the blood samples.

Original language	English
Pages (from-to)	80-88
Number of pages	9
Journal	Journal of Biotechnology
Volume	310
DOIs	https://doi.org/10.1016/j.jbiotec.2020.01.013
Publication status	Published - 20 Feb 2020

Keywords

Circulating nucleic acids
Host-based markers
Human sepsis diagnostics

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Biotechnology
Applied Microbiology and Biotechnology
Bioengineering

Fields of Expertise

Human- & Biotechnology
Information, Communication & Computing

Treatment code (Nähere Zuordnung)

Application

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10.1016/j.jbiotec.2020.01.013

Cite this

Ullrich, E., Heidinger, P., Soh, J., Villanova, L., Grabuschnig, S., Bachler, T., Hirschböck, E., Sánchez-Heredero, S., Ford, B., Sensen, M., Rosales Rodriguez, I., Schwendenwein, D., Neumeister, P., Zurl, C. J., Krause, R., Lorenz Khol, J., & Sensen, C. W. (2020). Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis. Journal of Biotechnology, 310, 80-88. https://doi.org/10.1016/j.jbiotec.2020.01.013

Ullrich, E, Heidinger, P, Soh, J, Villanova, L, Grabuschnig, S, Bachler, T, Hirschböck, E, Sánchez-Heredero, S, Ford, B, Sensen, M, Rosales Rodriguez, I, Schwendenwein, D, Neumeister, P, Zurl, CJ, Krause, R, Lorenz Khol, J & Sensen, CW 2020, 'Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis', Journal of Biotechnology, vol. 310, pp. 80-88. https://doi.org/10.1016/j.jbiotec.2020.01.013

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title = "Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis",

abstract = "We have identified 24 molecular markers, based on circulating nucleic acids (CNA) originating from the human genome, which in combination can be used in a quantitative real-time PCR (qPCR) assay to identify the presence of human sepsis, starting two to three days before the first clinical signs develop and including patients who meet the SEPSIS-3 criteria. The accuracy was more than 87% inside of the same patient cohort for which the markers were developed and up to 81% in blind studies of patient cohorts which were not included in the marker development. As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis. Our assay directly uses an aliquot of cell-free blood as the substrate for the PCR reaction, thus allowing to obtain the diagnostic results in three to four hours after the collection of the blood samples.",

keywords = "Circulating nucleic acids, Host-based markers, Human sepsis diagnostics",

author = "Elisabeth Ullrich and Petra Heidinger and Jung Soh and Laura Villanova and Stefan Grabuschnig and Thorsten Bachler and Elisabeth Hirschb{\"o}ck and Sara S{\'a}nchez-Heredero and Barry Ford and Maria Sensen and {Rosales Rodriguez}, Ingund and Daniel Schwendenwein and Peter Neumeister and Zurl, {Christoph J} and Robert Krause and {Lorenz Khol}, Johannes and Sensen, {Christoph W}",

note = "Copyright {\textcopyright} 2020. Published by Elsevier B.V.",

year = "2020",

month = feb,

day = "20",

doi = "10.1016/j.jbiotec.2020.01.013",

language = "English",

volume = "310",

pages = "80--88",

journal = "Journal of Biotechnology",

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AU - Ullrich, Elisabeth

AU - Heidinger, Petra

AU - Soh, Jung

AU - Villanova, Laura

AU - Grabuschnig, Stefan

AU - Bachler, Thorsten

AU - Hirschböck, Elisabeth

AU - Sánchez-Heredero, Sara

AU - Ford, Barry

AU - Sensen, Maria

AU - Rosales Rodriguez, Ingund

AU - Schwendenwein, Daniel

AU - Neumeister, Peter

AU - Zurl, Christoph J

AU - Krause, Robert

AU - Lorenz Khol, Johannes

AU - Sensen, Christoph W

PY - 2020/2/20

Y1 - 2020/2/20

N2 - We have identified 24 molecular markers, based on circulating nucleic acids (CNA) originating from the human genome, which in combination can be used in a quantitative real-time PCR (qPCR) assay to identify the presence of human sepsis, starting two to three days before the first clinical signs develop and including patients who meet the SEPSIS-3 criteria. The accuracy was more than 87% inside of the same patient cohort for which the markers were developed and up to 81% in blind studies of patient cohorts which were not included in the marker development. As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis. Our assay directly uses an aliquot of cell-free blood as the substrate for the PCR reaction, thus allowing to obtain the diagnostic results in three to four hours after the collection of the blood samples.

AB - We have identified 24 molecular markers, based on circulating nucleic acids (CNA) originating from the human genome, which in combination can be used in a quantitative real-time PCR (qPCR) assay to identify the presence of human sepsis, starting two to three days before the first clinical signs develop and including patients who meet the SEPSIS-3 criteria. The accuracy was more than 87% inside of the same patient cohort for which the markers were developed and up to 81% in blind studies of patient cohorts which were not included in the marker development. As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis. Our assay directly uses an aliquot of cell-free blood as the substrate for the PCR reaction, thus allowing to obtain the diagnostic results in three to four hours after the collection of the blood samples.

KW - Circulating nucleic acids

KW - Host-based markers

KW - Human sepsis diagnostics

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U2 - 10.1016/j.jbiotec.2020.01.013

DO - 10.1016/j.jbiotec.2020.01.013

M3 - Article

C2 - 32017954

SN - 0168-1656

VL - 310

SP - 80

EP - 88

JO - Journal of Biotechnology

JF - Journal of Biotechnology

ER -

Evaluation of Host-based Molecular Markers for the Early Detection of Human Sepsis

Abstract

Keywords

ASJC Scopus subject areas

Fields of Expertise

Treatment code (Nähere Zuordnung)

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