Integrated multi-omics analysis describes immune profiles in ischemic heart failure and identifies PTN as a novel biomarker.

IF 3.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-12-11 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1524827
Ting Xiong, Quhuan Li, Yifan Wang, Ying Kong, Hailin Li, Jie Liu, Yueheng Wu, Fengxia Zhang
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Abstract

Introduction: Heart failure is a leading global cause of mortality, with ischemic heart failure (IHF) being a major contributor. IHF is primarily driven by coronary artery disease, and its underlying mechanisms are not fully understood, particularly the role of immune responses and inflammation in cardiac muscle remodeling. This study aims to elucidate the immune landscape of heart failure using multi-omics data to identify biomarkers for preventing cardiac fibrosis and disease progression.

Methods: We utilized multi-omics data to elucidate the intricate immune landscape of heart failure at various regulatory levels. Given the substantial size of our transcriptomic dataset, we used diverse machine learning techniques to identify key mRNAs. For smaller datasets such as our proteomic dataset, we applied multilevel data cleansing and enhancement using principles from network biology. This comprehensive analysis led to the development of a scalable, integrated -omics analysis pipeline.

Results: Pleiotrophin (PTN) had shown significant upregulation in multiple datasets and the activation of various molecules associated with dysplastic cardiac remodeling. By synthesizing these data with experimental validations, PTN was identified as a potential biomarker.

Discussion: The present study not only provides a comprehensive perspective on immune dynamics in IHF but also offers valuable insights for the identification of biomarkers, discovery of therapeutic targets, and development of drugs.

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综合多组学分析描述了缺血性心力衰竭的免疫谱,并确定PTN是一种新的生物标志物。
心力衰竭是全球死亡的主要原因,其中缺血性心力衰竭(IHF)是一个主要原因。IHF主要由冠状动脉疾病引起,其潜在机制尚不完全清楚,特别是免疫反应和炎症在心肌重塑中的作用。本研究旨在利用多组学数据阐明心力衰竭的免疫景观,以识别预防心脏纤维化和疾病进展的生物标志物。方法:我们利用多组学数据来阐明心力衰竭在不同调控水平上的复杂免疫景观。鉴于转录组学数据集的庞大规模,我们使用了多种机器学习技术来识别关键mrna。对于较小的数据集,如我们的蛋白质组学数据集,我们使用网络生物学的原理应用多层数据清理和增强。这种全面的分析导致了可扩展的、集成的组学分析管道的发展。结果:多营养蛋白(PTN)在多个数据集中显示出显著上调,并激活了与心脏重构异常相关的各种分子。通过综合这些数据和实验验证,PTN被确定为潜在的生物标志物。讨论:本研究不仅为IHF的免疫动力学提供了一个全面的视角,而且为生物标志物的鉴定、治疗靶点的发现和药物的开发提供了有价值的见解。
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来源期刊
Frontiers in Molecular Biosciences
Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
7.20
自引率
4.00%
发文量
1361
审稿时长
14 weeks
期刊介绍: Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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