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Novel Signature Genes and Pathways Identified for Human Left Ventricle Cardiomyopathies Rise from Different Etiologies

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Novel Signature Genes and Pathways Identified for Human Left Ventricle Cardiomyopathies Rise from Different Etiologies ISSN: 2581-7388 Journal of Inno Biomedical Research and Reviews Volume 4: 1 Journal of Applied Microbiological ResearchJ Biomed Res Rev 2021 Novel Signature Genes and Pathways Identified for Human Left Ventricle Cardiomyopathies Rise from different Etiologies 1State Key Laboratory of Phytochemistry and Plant Resources in West China, Jiao Tian1,2† Kunming Institute of Botany, Chinese Academy of Sciences, PR China Zheng Yuan Wu1† 2School of Life Sciences, Yunnan University, China Ying Ying He*3 3School of Chemical Science & Technology, Yunnan University, China Shubai Liu*1 †These authors contributed equally to this work Abstract Article Information Cardiomyopathy, a heart disease that arises from different Article Type: Research Article etiologies, places a huge burden on global health care society. Clinical Article Number: JBRR-150 cases of cardiomyopathy were examined independently from the Received Date: 12 May, 2021 genomic database to identify potential biomarkers and pathways for Accepted Date: 11 June, 2021 cardiomyopathy. Exploration of these biopsies as a whole transcription Published Date: 19 June, 2021 disorder pattern by WGCNA (Weighted Gene Co-expression Network Analysis) to discover signature genes for different cardiomyopathy subtypes. Narrow genes and key pathways correlated with *Corresponding author: Shubai Liu, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese and protein-protein interaction (PPI) network enrichment analysis. Academy of Sciences, 132 Blue Black Street, Kunming, Discoveredcardiomyopathy hub genestraits have been blastidentified through through the Cardiovascularco-expression 650201 Yunnan, PR China. Tel: +86 871-65223309; Disease Portal to verify human cardiomyopathy-related functions. E-mail: [email protected] subtypes of cardiomyopathy: 1) Four common genes (MDM4, CFLAR, Ying Ying He, School of Chemical Science & Technology, Three common axes of signature genes have been identified for five Yunnan University, Kunming, Yunnan 650091, China. cardiomyopathy subgroups; 2) Subtypes of cardiomyopathy (ischemic, E-mail: [email protected] post.RPS6KB1, partum, PKD1L2) familiar have and idiopathic)been identified have been for ischemicshared with and eight ischemic genes (MAPK1, MAPK11, MAPK14, LMNA, RAC1, PECAM1, XIAP, CREB1); 3) Citation: Liu S, He YY, Wu ZY, Tian J (2021) Novel Signature Genes and Pathways Identified for Human Left subtypes of cardiomyopathy (viral, post. partum, familiar, and idiopathic) Ventricle Cardiomyopathies Rise from different Etiologies. (viral,TFAM andpost. RHEB partum, have familiar, been identified and idiopathic). as the common Major enrichedsignature pathways genes for J Biomed Res Rev Vol: 4, Issu: 1. (31-50). included the MAPK signaling pathway, the protein processing pathway in the endoplasmic reticulum, and so on. Abnormally regulating these Copyright: © 2021 Liu S. This is an open-access article signature genes and pathways caused metabolic process disorders and distributed under the terms of the Creative Commons cellular malfunctions that generally contribute to cardiac dysregulation Attribution License, which permits unrestricted use, and functional relapse into cardiomyopathies. In summary, these novel distribution, and reproduction in any medium, provided the original author and source are credited. signature genes may work as potential biomarkers for the diagnosis of Keywords: Heart failure; Cardiomyopathy; Ventricle cardiomyocytes; cardiomyopathy and benefit patients with improved outcomes. WGCNA; Signature gene. List of Abbreviations: PCA--principal component analysis; GO-- MM--module membership ; ME--module eigengene; MS--module gene ontology; TOM--Topological Overlap Matrix ; GS--gene significance; ID--idiopathic dilated; IS--ischemic; IDCM--idiopathic cardiomyopathy; FCM--familialsignificance; WGCNA--weighted cardiomyopathy; genePCM--post-partum co-expression networkcardiomyopathy; analysis; ISCM--ischemic cardiomyopathy; VCM--viral cardiomyopathy. Introduction Cardiomyopathy is characterized by the inability of the heart to pump and/or to fill blood as required by the body, and the worst state www. innovationinfo. org lapses into heart failure, a complex pathophysiological than 20 cases), variety of subgroups of cardiomyopathy, condition with left ventricle myocytes dysfunction. Globally, and clearly annotations with clinical trials were the major at least 26 million people have suffered from heart failure metrics for screening. A dataset, with a GEO tracking number and have spent more than $30 billion on health in the world GSE1145 and a platform entry number GPL570 (https:// , year period [2]. Although cardiomyopathy is the primary was screened out for further analysis. In this datasets, cardiac condition[1]. Mortality for ofheart heart failure, failure pathogenic is as high asdamages ~50% over(abnormal a five- www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114 5) physical structure and dysfunction) has often occurred patients of who were undergoing heart failure and planed fortranscription a cardiac profilestransplantation. were established Human leftfrom ventricle cardiomyopathy samples of biomarkers may be very useful for early diagnosis of were collected from biopsies of cardiomyopathy patients, or cardiomyopathy,in the patient’s interruption cardiomyopathy of the diseasetissue. processionIdentification to from “normal” organ donors whose hearts cannot be used heart failure, and reduction of the mortality. for transplants. The heart failure of these cardiomyopathy patients arises from different etiologies (Supplementary Cardiomyopathy etiologies are multiple factors, which make cardiomyopathy a heterogeneous complex Affymetrix Human Genome U133 Plus 2.0 Array. Changes cardiovascular disease. Major stimuli include changing Table.1). The transcriptional profiles were measured by physiological conditions (such as pregnancy and delivery) and stressful pathological conditions (for example, transplantation.in transcriptional Sample profiles collection were andcorrelated microarray with dataset the ischemia, hypertension, diabetes, viral infection, and so werephysiologic performed profile by ofthe failure cardio-genomics hearts acquired lab, Department at the time of on). Cardiomyopathy is divided into several subgroups, Bauer Center for Genomic Research, Harvard University. according to the distinct etiologies [3]. The most common Construction of weighted gene co-expression network subtypeswhich usually are hypertrophichave specific cardiomyopathymorphological features,(HCM), WGCNA package of R (version 1.63) was downloaded dilated cardiomyopathy (DCM), viral cardiomyopathy (http://www.Rproject.org) and setup by following the (VCM), familial cardiomyopathy (FCM), post-partum protocol previously [9]. Each gene expression value from cardiomyopathy (PCM) and ischemic cardiomyopathy the downloaded dataset (GSE1145) was normalized by compared with inter reference genes, and performed a cardiomyopathic cases caused by abnormal gene expression, without(ISCM)(3). somatic Early genetic clinical alteration, investigations indicating have the identifiedimpact of sample clustering according to the distance between epigenetics and transcriptional changes on cardiomyopathy differentlog2 transformation. samples in Pearson’s Microarray correlation quality matrices. was tested Outliers by [4]. Complex etiologies, however, can lead to a variety of samples with excessive missing values were excluded from common cardiomyopathy biomarkers with limited number were identified with a height cut of 170000. Outliers and cases.abnormal expression genes, making it difficult to identify component analysis (PCA). The co-expression network was Computerization methodologies have been applied to next analysis. Data quality was checked by the principal the discovery of signature genes as potential biomarkers that R2 of diseases. Among many computerization methodologies, isconstructed, close to a settingscale-free the network.soft threshold The plotβ = 7,of whichlog10 means(p(k)) the Weighted Gene Co-expression Network Analysis versus islog10(k) equal to 0.98(Supplementary and indicates Figure the constructed S2A&B) indicates network (WGCNA) is a useful approach that analyzes gene expression functional features, and to discover the genetic disorders that the network is close to a scale-free network by using β inprofiling diseases to [5].find WGCNA out co-expression has been widely network used based in screening on their = 7, where k is the whole network connectivity and p(k) is novel biomarkers of cancers and has been demonstrated to the corresponding frequency distribution (Supplementary be a reliable and powerful tool [6-8]. In this study, WGCNA Table 2). Once β value was determined, the Topological dissTOM.Overlap Matrix The hierarchical (TOM) and dissTOM clustering = 1−TOManalysis were was obtained used to several cardiomyopathies, containing 90 human biopsies identifyautomatically. gene modules Modules and were color identified to indicate based modules, on TOM which and fromwas employedGEO databases to analyze in NCBI. the Genesgene expressionhave been discoveredprofiles of is a cluster of densely interconnected genes in terms of co- expression. Genes that were not co-expressed were assigned p-value of candidate WGCNAthat significantly were further associated validated with through cardiomyopathies. bioportal database, The genes was calculated via T-test. The association between the ansignature independent
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