由鸟分枝杆菌亚种引起的约翰氏病。副结核病（MAP）是乳制品行业的主要关注点。因为,该病的发病机制尚不清楚，有必要开发一种方法来高度自信地发现这种疾病背后的分子机制。生物学研究经常遇到重复性问题。缺乏从不同的数据集中找到稳定的共表达网络模块的方法，这促使我们提出一个计算管道来识别未保留的共识模块。分析了与MAP感染相关的两个RNA-Seq数据集，和共识模块被检测并进行保存分析。两个数据集中的未保留的共识模块被确定为其连通性和密度受疾病影响的模块。鉴定了未保留的共有模块中的长链非编码RNA(lncRNA)和TF基因以构建lncRNA-mRNA-TF的整合网络。这些网络由蛋白质-蛋白质相互作用(PPIs)网络证实。此外，两个数据集之间重叠的hub基因被认为是共识模块的hub基因.在66个共识模块中，21个模块是未保留的共识模块，在两个数据集中都很常见，619个hub基因是这些模块的成员。此外，在12个和19个未保留的共有模块中鉴定了34个lncRNA和152个TF基因，分别。17个未保留共识模块中的预测PPI具有重要意义，在共表达和PPI网络中通常鉴定出283个hub基因。功能富集分析显示，21个模块中有8个显著富集了与约翰病相关的生物过程，包括炎症反应，\"\"白细胞介素-1介导的信号通路\",“I型干扰素信号通路，“”细胞因子介导的信号通路，“\”干扰素β生产的调节，“和”对干扰素-γ的反应。\"此外，一些基因(hubmRNA，TF,和lncRNA）被引入作为约翰疾病发病机理的潜在候选者，例如TLR2，NFKB1，IRF1，ATF3，TREM1，CDH26，HMGB1，STAT1，ISG15，CASS3。这项研究扩大了我们对约翰病分子机制的认识，提出的管道使我们能够取得更多有效的结果。
Johne\'s disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) is a major concern in dairy industry. Since, the pathogenesis of the disease is not clearly known, it is necessary to develop an approach to discover molecular mechanisms behind this disease with high confidence. Biological studies often suffer from issues with reproducibility. Lack of a method to find stable modules in co-expression networks from different datasets related to Johne\'s disease motivated us to present a computational pipeline to identify non-preserved consensus modules. Two RNA-Seq datasets related to MAP infection were analyzed, and
consensus modules were detected and were subjected to the preservation analysis. The non-preserved
consensus modules in both datasets were determined as they are modules whose connectivity and density are affected by the disease. Long non-coding RNAs (lncRNAs) and TF genes in the non-preserved
consensus modules were identified to construct integrated networks of lncRNA-mRNA-TF. These networks were confirmed by protein-protein interactions (PPIs) networks. Also, the overlapped hub genes between two datasets were considered hub genes of the
consensus modules. Out of 66
consensus modules, 21 modules were non-preserved
consensus modules, which were common in both datasets and 619 hub genes were members of these modules. Moreover, 34 lncRNA and 152 TF genes were identified in 12 and 19 non-preserved consensus modules, respectively. The predicted PPIs in 17 non-preserved consensus modules were significant, and 283 hub genes were commonly identified in both co-expression and PPIs networks. Functional enrichment analysis revealed that eight out of 21 modules were significantly enriched for biological processes associated with Johne\'s disease including \"inflammatory response,\" \"interleukin-1-mediated signaling pathway\", \"type I interferon signaling pathway,\" \"cytokine-mediated signaling pathway,\" \"regulation of interferon-beta production,\" and \"response to interferon-gamma.\" Moreover, some genes (hub mRNA, TF, and lncRNA) were introduced as potential candidates for Johne\'s disease pathogenesis such as TLR2, NFKB1, IRF1, ATF3, TREM1, CDH26, HMGB1, STAT1, ISG15, CASP3. This study expanded our knowledge of molecular mechanisms involved in Johne\'s disease, and the presented pipeline enabled us to achieve more valid results.
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