Heart failure (HF) is the end stage of most heart disease cases and can be initiated from multiple aetiologies. However, whether the molecular basis of HF has a commonality between different aetiologies has not been elucidated. To address this lack, we performed a three‐tiered analysis by integrating transcriptional data and pathway information to explore the commonalities of HF from different aetiologies. First, through differential expression analysis, we obtained 111 genes that were frequently differentially expressed in HF from 11 different aetiologies. Several genes, such as NPPA and NPPB , are early and accurate biomarkers for HF. We also provided candidates for further experimental verification, such as SERPINA3 and STAT4 . Then, using gene set enrichment analysis, we successfully identified 19 frequently dysregulated pathways. In particular, we found that pathways related to immune system signalling, the extracellular matrix and metabolism were critical in the development of HF. Finally, we successfully acquired 241 regulatory relationships between 64 transcriptional factors (TFs) and 17 frequently dysregulated pathways by integrating a regulatory network, and some of the identified TFs have already been proven to play important roles in HF. Taken together, the three‐tiered analysis of HF provided a systems biology perspective on HF and emphasized the molecular commonality of HF from different aetiologies.

中文翻译：

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转录数据的三层综合分析揭示了来自不同病因的与心力衰竭相关的共享途径。

心力衰竭（HF）是大多数心脏病病例的终末期，可以由多种病因引发。然而，HF的分子基础是否在不同病因之间具有共同性尚未阐明。为了解决这一不足，我们通过整合转录数据和途径信息进行了三层分析，以探讨来自不同病因的HF的共性。首先，通过差异表达分析，我们从11种不同病因中获得了111种在HF中经常差异表达的基因。几个基因，例如NPPA和NPPB，是HF的早期且准确的生物标记。我们还提供了用于进一步实验验证的候选人，例如SERPINA3和STAT4。然后，使用基因集富集分析，我们成功鉴定出19条频繁失调的途径。特别是，我们发现与免疫系统信号传导，细胞外基质和代谢有关的途径在HF的发展中至关重要。最终，我们通过整合调控网络成功地获得了64个转录因子（TF）与17个经常失调的途径之间的241个调控关系，并且已证明某些鉴定出的TF在HF中起重要作用。总之，对HF的三层分析为HF提供了系统生物学的观点，并强调了来自不同病因的HF的分子共性。