Aims: Transcriptomic studies have contributed to fundamental knowledge of myocardial remodeling in human heart failure (HF). However, the agreement on key regulated genes in HF is limited and systematic efforts to integrate evidence from multiple patient cohorts are lacking. Here we aimed to provide an unbiased consensus transcriptional signature of human end-stage HF by comprehensive comparison and analysis of publicly available datasets. Methods and Results: We curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts. Transfer learning approaches revealed conserved disease patterns across all studies independent of technical differences. We meta-analyzed the dysregulation of 14041 genes to extract a consensus signature of HF. Estimation of the activities of 343 transcription factors, 14 signalling pathways, and 182 micro RNAs, as well as the enrichment of 5998 biological processes confirmed the established aspects of the functional landscape of the disease and revealed novel ones. We provide all results in a free public resource https://saezlab.shinyapps.io/reheat/ to facilitate further use and interpretation of the results. We exemplify usage by deciphering fetal gene reprogramming and tracing myocardial origin of the plasma proteome biomarkers in HF patients. Conclusion: We demonstrated the feasibility of combining transcriptional studies from different HF patient cohorts. This compendium provides a robust and consistent collection of molecular markers of end-stage HF that may guide the identification of novel targets with diagnostic or therapeutic relevance. Keywords: Heart Failure, Transcriptomics, Transfer Learning, Knowledge Banks, Consensus Signature, Meta-Analysis

中文翻译：

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人类末期心力衰竭的共识转录景观

目的：转录组学研究为人类心力衰竭（HF）中心肌重塑的基础知识做出了贡献。然而，关于心衰中关键调控基因的共识是有限的，并且缺乏整合来自多个患者队列的证据的系统性努力。在这里，我们旨在通过对公开可用数据集进行全面比较和分析，为人类末期HF提供无偏见的共识转录签名。方法和结果：我们策划并统一处理了来自263例健康人和653例衰竭人心脏的左心室样本的16个公开转录组研究。转移学习方法揭示了所有研究中保守的疾病模式，而与技术差异无关。我们荟萃分析了14041基因的失调，以提取HF的共识签名。估计343个转录因子，14个信号通路和182个微RNA的活性，以及​​丰富的5998个生物过程，证实了该疾病功能格局的既定方面，并揭示了新的方面。我们在免费的公共资源中提供所有结果，网址为https://saezlab.shinyapps.io/reheat/，以方便进一步使用和解释结果。我们通过破译胎儿基因重编程和追踪HF患者血浆蛋白质组生物标志物的心肌来源来举例说明用法。结论：我们证明了结合来自不同HF患者队列的转录研究的可行性。该简编提供了一个稳定且一致的终末期HF分子标记物集合，可指导对具有诊断或治疗意义的新靶标进行鉴定。