Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy

IntroductionHeart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).MethodsOmics data were accessed through GEO...

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Main Authors: Konstantina Portokallidou, Nikolas Dovrolis, Georgia Ragia, Natalia Atzemian, George Kolios, Vangelis G. Manolopoulos
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1115623/full
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author Konstantina Portokallidou
Konstantina Portokallidou
Nikolas Dovrolis
Nikolas Dovrolis
Georgia Ragia
Georgia Ragia
Natalia Atzemian
Natalia Atzemian
George Kolios
George Kolios
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
author_facet Konstantina Portokallidou
Konstantina Portokallidou
Nikolas Dovrolis
Nikolas Dovrolis
Georgia Ragia
Georgia Ragia
Natalia Atzemian
Natalia Atzemian
George Kolios
George Kolios
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
author_sort Konstantina Portokallidou
collection DOAJ
description IntroductionHeart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).MethodsOmics data were accessed through GEO repository for transcriptomic and PRIDE repository for proteomic datasets. Sets of differentially expressed genes and proteins comprising DCM (DiSig) and ICM (IsSig) signatures were analyzed by a multilayered bioinformatics approach. Enrichment analysis via the Gene Ontology was performed through the Metascape platform to explore biological pathways. Protein-protein interaction networks were analyzed via STRING db and Network Analyst.ResultsIntersection of transcriptomic and proteomic analysis showed 10 differentially expressed genes/proteins in DiSig (AEBP1, CA3, HBA2, HBB, HSPA2, MYH6, SERPINA3, SOD3, THBS4, UCHL1) and 15 differentially expressed genes/proteins in IsSig (AEBP1, APOA1, BGN, CA3, CFH, COL14A1, HBA2, HBB, HSPA2, LTBP2, LUM, MFAP4, SOD3, THBS4, UCHL1). Common and distinct biological pathways between DiSig and IsSig were retrieved, allowing for their molecular characterization. Extracellular matrix organization, cellular response to stress and transforming growth factor-beta were common between two subphenotypes. Muscle tissue development was dysregulated solely in DiSig, while immune cells activation and migration in IsSig.DiscussionOur bioinformatics approach sheds light on the molecular background of HF etiopathology showing molecular similarities as well as distinct expression differences between DCM and ICM. DiSig and IsSig encompass an array of “cross-validated” genes at both transcriptomic and proteomic level, which can serve as novel pharmacological targets and possible diagnostic biomarkers.
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spelling doaj.art-33ca60d130854fb7a83b48f9090451452023-02-13T05:02:10ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-02-011010.3389/fcvm.2023.11156231115623Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathyKonstantina Portokallidou0Konstantina Portokallidou1Nikolas Dovrolis2Nikolas Dovrolis3Georgia Ragia4Georgia Ragia5Natalia Atzemian6Natalia Atzemian7George Kolios8George Kolios9Vangelis G. Manolopoulos10Vangelis G. Manolopoulos11Vangelis G. Manolopoulos12Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceLaboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceLaboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceLaboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceLaboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceLaboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, GreeceIndividualised Medicine and Pharmacological Research Solutions Center, Alexandroupolis, GreeceClinical Pharmacology Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, GreeceIntroductionHeart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).MethodsOmics data were accessed through GEO repository for transcriptomic and PRIDE repository for proteomic datasets. Sets of differentially expressed genes and proteins comprising DCM (DiSig) and ICM (IsSig) signatures were analyzed by a multilayered bioinformatics approach. Enrichment analysis via the Gene Ontology was performed through the Metascape platform to explore biological pathways. Protein-protein interaction networks were analyzed via STRING db and Network Analyst.ResultsIntersection of transcriptomic and proteomic analysis showed 10 differentially expressed genes/proteins in DiSig (AEBP1, CA3, HBA2, HBB, HSPA2, MYH6, SERPINA3, SOD3, THBS4, UCHL1) and 15 differentially expressed genes/proteins in IsSig (AEBP1, APOA1, BGN, CA3, CFH, COL14A1, HBA2, HBB, HSPA2, LTBP2, LUM, MFAP4, SOD3, THBS4, UCHL1). Common and distinct biological pathways between DiSig and IsSig were retrieved, allowing for their molecular characterization. Extracellular matrix organization, cellular response to stress and transforming growth factor-beta were common between two subphenotypes. Muscle tissue development was dysregulated solely in DiSig, while immune cells activation and migration in IsSig.DiscussionOur bioinformatics approach sheds light on the molecular background of HF etiopathology showing molecular similarities as well as distinct expression differences between DCM and ICM. DiSig and IsSig encompass an array of “cross-validated” genes at both transcriptomic and proteomic level, which can serve as novel pharmacological targets and possible diagnostic biomarkers.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1115623/fullheart failuredilated cardiomyopathyischemic cardiomyopathyprecision medicineproteomicstranscriptomics
spellingShingle Konstantina Portokallidou
Konstantina Portokallidou
Nikolas Dovrolis
Nikolas Dovrolis
Georgia Ragia
Georgia Ragia
Natalia Atzemian
Natalia Atzemian
George Kolios
George Kolios
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
Vangelis G. Manolopoulos
Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
Frontiers in Cardiovascular Medicine
heart failure
dilated cardiomyopathy
ischemic cardiomyopathy
precision medicine
proteomics
transcriptomics
title Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
title_full Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
title_fullStr Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
title_full_unstemmed Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
title_short Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
title_sort multi omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy
topic heart failure
dilated cardiomyopathy
ischemic cardiomyopathy
precision medicine
proteomics
transcriptomics
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1115623/full
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