Data_Sheet_5_A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling.zip

Our understanding of the transition from physiological to pathological cardiac hypertrophy remains elusive and largely based on reductionist hypotheses. Here, we profiled the translatomes of 15 mouse hearts to provide a molecular blueprint of altered gene networks in early cardiac remodeling. Using co-expression analysis, we showed how sub-networks are orchestrated into functional modules associated with pathological phenotypes. We discovered unappreciated hub genes, many undocumented for their role in cardiac hypertrophy, and genes in the transcriptional network that were rewired in the translational network, and associated with semantically different subsets of enriched functional terms, such as Fam210a, a novel musculoskeletal modulator, or Psmd12, implicated in protein quality control. Using their correlation structure, we found that transcriptome networks are only partially reproducible at the translatome level, providing further evidence of post-transcriptional control at the level of translation. Our results provide novel insights into the complexity of the organization of in vivo cardiac regulatory networks.

目前学界对生理性心脏肥厚向病理性心脏肥厚的转变机制仍不甚明晰，相关认知大多基于还原论假说。本研究对15个小鼠心脏的翻译组（translatome）进行了谱分析，以构建早期心脏重构中基因网络改变的分子蓝图。通过共表达分析，本研究揭示了子网如何协同组装为与病理表型相关的功能模块。本研究发现了一批此前未被关注的枢纽基因，其中多数尚未见报道与心脏肥厚相关；同时还鉴定出转录网络中在翻译组层面发生重连的基因，这些基因与富集功能术语的语义不同子集相关，例如新型肌肉骨骼调控因子Fam210a，以及参与蛋白质质量控制的Psmd12。基于基因的相关结构分析，本研究发现转录组网络在翻译组层面仅能部分重现，这为翻译层面的转录后调控提供了进一步的实验证据。本研究结果为解析体内心脏调控网络的组织复杂性提供了全新视角。