Peptidome profiling for the immunological stratification in sepsis: a proof of concept study

Autores
Ledesma, Martin Manuel; Todero, Maria Florencia; Maceira, Lautaro; Prieto, Monica; Vay, Carlos; Galas, Marcelo Fabián; López, Beatriz; Yokobori, Noemí; Rearte, María Bárbara
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.
Fil: Ledesma, Martin Manuel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Maceira, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Prieto, Monica. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina
Fil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina
Fil: Galas, Marcelo Fabián. Organización Panamericana de la Salud; Estados Unidos
Fil: López, Beatriz. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina
Fil: Yokobori, Noemí. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
MALDI-TOF
Sepsis
Peptidome
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/201520

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spelling Peptidome profiling for the immunological stratification in sepsis: a proof of concept studyLedesma, Martin ManuelTodero, Maria FlorenciaMaceira, LautaroPrieto, MonicaVay, CarlosGalas, Marcelo FabiánLópez, BeatrizYokobori, NoemíRearte, María BárbaraMALDI-TOFSepsisPeptidomehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.Fil: Ledesma, Martin Manuel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Maceira, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Prieto, Monica. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; ArgentinaFil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Galas, Marcelo Fabián. Organización Panamericana de la Salud; Estados UnidosFil: López, Beatriz. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; ArgentinaFil: Yokobori, Noemí. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaNature Publishing Group2022-07-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201520Ledesma, Martin Manuel; Todero, Maria Florencia; Maceira, Lautaro; Prieto, Monica; Vay, Carlos; et al.; Peptidome profiling for the immunological stratification in sepsis: a proof of concept study; Nature Publishing Group; Scientific Reports; 12; 1; 6-7-2022; 1-82045-23222045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-022-15792-5#Sec2info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-022-15792-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:59Zoai:ri.conicet.gov.ar:11336/201520instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:59.501CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
title Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
spellingShingle Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
Ledesma, Martin Manuel
MALDI-TOF
Sepsis
Peptidome
title_short Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
title_full Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
title_fullStr Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
title_full_unstemmed Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
title_sort Peptidome profiling for the immunological stratification in sepsis: a proof of concept study
dc.creator.none.fl_str_mv Ledesma, Martin Manuel
Todero, Maria Florencia
Maceira, Lautaro
Prieto, Monica
Vay, Carlos
Galas, Marcelo Fabián
López, Beatriz
Yokobori, Noemí
Rearte, María Bárbara
author Ledesma, Martin Manuel
author_facet Ledesma, Martin Manuel
Todero, Maria Florencia
Maceira, Lautaro
Prieto, Monica
Vay, Carlos
Galas, Marcelo Fabián
López, Beatriz
Yokobori, Noemí
Rearte, María Bárbara
author_role author
author2 Todero, Maria Florencia
Maceira, Lautaro
Prieto, Monica
Vay, Carlos
Galas, Marcelo Fabián
López, Beatriz
Yokobori, Noemí
Rearte, María Bárbara
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MALDI-TOF
Sepsis
Peptidome
topic MALDI-TOF
Sepsis
Peptidome
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.
Fil: Ledesma, Martin Manuel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Maceira, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Prieto, Monica. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina
Fil: Vay, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina
Fil: Galas, Marcelo Fabián. Organización Panamericana de la Salud; Estados Unidos
Fil: López, Beatriz. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina
Fil: Yokobori, Noemí. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Sepsis has been called the graveyard of pharmaceutical companies due to the numerous failed clinical trials. The lack of tools to monitor the immunological status in sepsis constrains the development of therapies. Here, we evaluated a test based on whole plasma peptidome acquired by MALDI-TOF-mass spectrometer and machine-learning algorithms to discriminate two lipopolysaccharide-(LPS) induced murine models emulating the pro- and anti-inflammatory/immunosuppression environments that can be found during sepsis. The LPS group was inoculated with a single high dose of LPS and the IS group was subjected to increasing doses of LPS, to induce proinflammatory and anti-inflammatory/immunosuppression profiles respectively. The LPS group showed leukopenia and higher levels of cytokines and tissue damage markers, and the IS group showed neutrophilia, lymphopenia and decreased humoral response. Principal component analysis of the plasma peptidomes formed discrete clusters that mostly coincided with the experimental groups. In addition, machine-learning algorithms discriminated the different experimental groups with a sensitivity of 95.7% and specificity of 90.9%. Data reveal the potential of plasma fingerprints analysis by MALDI-TOF-mass spectrometry as a simple, speedy and readily transferrable method for sepsis patient stratification that would contribute to therapeutic decision-making based on their immunological status.
publishDate 2022
dc.date.none.fl_str_mv 2022-07-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/201520
Ledesma, Martin Manuel; Todero, Maria Florencia; Maceira, Lautaro; Prieto, Monica; Vay, Carlos; et al.; Peptidome profiling for the immunological stratification in sepsis: a proof of concept study; Nature Publishing Group; Scientific Reports; 12; 1; 6-7-2022; 1-8
2045-2322
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201520
identifier_str_mv Ledesma, Martin Manuel; Todero, Maria Florencia; Maceira, Lautaro; Prieto, Monica; Vay, Carlos; et al.; Peptidome profiling for the immunological stratification in sepsis: a proof of concept study; Nature Publishing Group; Scientific Reports; 12; 1; 6-7-2022; 1-8
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-022-15792-5
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