Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches

Abstract The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive bioma...

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Autores principales:	S. Y. Liao, N. G. Casanova, C. Bime, S. M. Camp, H. Lynn, Joe G. N. Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8dbbd029da3342b6ac531298d917c949
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spelling	oai:doaj.org-article:8dbbd029da3342b6ac531298d917c9492021-12-02T18:14:39ZIdentification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches10.1038/s41598-021-98053-12045-2322https://doaj.org/article/8dbbd029da3342b6ac531298d917c9492021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98053-1https://doaj.org/toc/2045-2322Abstract The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.S. Y. LiaoN. G. CasanovaC. BimeS. M. CampH. LynnJoe G. N. GarciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. Y. Liao N. G. Casanova C. Bime S. M. Camp H. Lynn Joe G. N. Garcia Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
description	Abstract The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.
format	article
author	S. Y. Liao N. G. Casanova C. Bime S. M. Camp H. Lynn Joe G. N. Garcia
author_facet	S. Y. Liao N. G. Casanova C. Bime S. M. Camp H. Lynn Joe G. N. Garcia
author_sort	S. Y. Liao
title	Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
title_short	Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
title_full	Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
title_fullStr	Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
title_full_unstemmed	Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches
title_sort	identification of early and intermediate biomarkers for ards mortality by multi-omic approaches
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8dbbd029da3342b6ac531298d917c949
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Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches

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