研究科: 千葉大学大学院自然科学研究科博士(学術)報告番号:甲第学287

Ayodele A. Alaiya (3202194)

Dilek Colak (32197)

Editha Andres (3202200)

Namik Kaya (347797)

Nduna Dzimiri (3123975)

Nzioka P. Muiya (3202188)

Olfat AlHarazi (3202191)

Zakia Shinwari (3202197)

PLoS ONE

PubMed

AimsThe disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery.MethodsWe used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system.ResultsWe identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6, HSP90AA1, and ATP5C1 (pConclusionThe concomitant use of transcriptome and proteome expression to evaluate global changes in DCM has led to the identification of sixteen commonly altered entities as well as novel genes, proteins and pathways whose cardiac functions have yet to be deciphered. This data should contribute towards better management of the disease.</div

The Francis Crick Institute

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy

Venn diagrams representing overlap of (A) predicted upstream regulators, (B) enriched GO biological processes, and (C) KEGG pathways between differentially expressed genes and proteins.</p

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy - Fig 7

(A) Venn diagram representing the overlapping between the differentially expressed proteins and genes. Sixteen proteins/genes were commonly identified in both global gene and protein profiling. (B) Unsupervised principal component analysis (PCA) of the commonly dysregulated proteins/genes separating samples into DCM patients and normal controls. The blue spheres refer to DCM patients and red normal controls. (C-D) Unsupervised two-dimensional hierarchical clustering of proteomic and transcriptomic datasets using commonly dysregulated proteins/genes (C and D, respectively). The hierarchical clustering revealed two main clusters, one composed of DCM patients and another composed of normal controls. Highly expressed genes are indicated in red, intermediate in black, and weakly expressed in green.</p

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy - Fig 2

Dilek Colak

Ayodele A. Alaiya

Namik Kaya

Nzioka P. Muiya

Olfat AlHarazi

Zakia Shinwari

Editha Andres

Nduna Dzimiri

Crossref

AIMS:The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS:We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system. RESULTS:We identified 1262 differentially expressed genes (DEGs) and 269 proteins (DEPs) between DCM cases and healthy controls. Among the most significantly upregulated (>5-fold) proteins were GRK5, APOA2, IGHG3, ANXA6, HSP90AA1, and ATP5C1 (p< 0.01). On the other hand, the most significantly downregulated proteins were GSTM5, COX17, CAV1 and ANXA3. At least ten entities were concomitantly upregulated on the two analysis platforms: GOT1, ALDH4A1, PDHB, BDH1, SLC2A11, HSP90AA1, HSP90AB1, H2AFV, HSPA5 and NDUFV1. Gene ontology analyses of DEGs and DEPs revealed significant overlap with enrichment of genes/proteins related to metabolic process, biosynthetic process, cellular component organization, oxidative phosphorylation, alterations in glycolysis and ATP synthesis, Alzheimer's disease, chemokine-mediated inflammation and cytokine signalling pathways. CONCLUSION:The concomitant use of transcriptome and proteome expression to evaluate global changes in DCM has led to the identification of sixteen commonly altered entities as well as novel genes, proteins and pathways whose cardiac functions have yet to be deciphered. This data should contribute towards better management of the disease

Ayodele A Alaiya

Nzioka P Muiya

Directory of Open Access Journals

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy.

(A) Unsupervised principal component analysis (PCA) clearly distinguishing DCM patients from normal controls. The blue spheres refer to DCM patients, and red normal controls. (B) Heatmap of genes that were significantly modulated in DCM. Hierarchical clustering distinguished individuals as either DCM or normal controls. Red and green denote highly and weakly expressed genes, respectively.</p

Integrated Left Ventricular Global Transcriptome and Proteome Profiling in Human End-Stage Dilated Cardiomyopathy - Fig 1

https://figshare.com/articles/Integrated_Left_Ventricular_Global_Transcriptome_and_Proteome_Profiling_in_Human_End-Stage_Dilated_Cardiomyopathy_-_Fig_2/3997728