Studio of Computational Biology & Bioinformatics, CSIR-IHBT, Palampur, HP, India.
Academy of Scientific and Innovative Research (AcSIR), Chennai, TN, India.
Sci Rep. 2017 May 8;7(1):1554. doi: 10.1038/s41598-017-01765-6.
Idiopathic Pulmonary Fibrosis (IPF) is an incurable progressive fibrotic disease of the lungs. We currently lack a systematic understanding of IPF biology and a systems approach may offer new therapeutic insights. Here, for the first time, a large volume of high throughput genomics data has been unified to derive the most common molecular signatures of IPF. A set of 39 differentially expressed genes (DEGs) was found critical to distinguish IPF. Using high confidence evidences and experimental data, system level networks for IPF were reconstructed, involving 737 DEGs found common across at least two independent studies. This all provided one of the most comprehensive molecular system views for IPF underlining the regulatory and molecular consequences associated. 56 pathways crosstalks were identified which included critical pathways with specified directionality. The associated steps gained and lost due to crosstalk during IPF were also identified. A serially connected system of five crucial genes was found, potentially controlled by nine miRNAs and eight transcription factors exclusively in IPF when compared to NSIP and Sarcoidosis. Findings from this study have been implemented into a comprehensive molecular and systems database on IPF to facilitate devising diagnostic and therapeutic solutions for this deadly disease.
特发性肺纤维化（IPF）是一种无法治愈的进行性肺纤维化疾病。我们目前对 IPF 的生物学缺乏系统的了解，而系统方法可能会提供新的治疗见解。在这里，我们首次将大量高通量基因组学数据统一起来，得出 IPF 最常见的分子特征。发现一组 39 个差异表达基因（DEGs）对于区分 IPF 至关重要。使用高可信度证据和实验数据，我们重建了 IPF 的系统级网络，其中涉及至少两个独立研究中发现的 737 个共同的 DEGs。这为 IPF 提供了最全面的分子系统视图之一，强调了相关的调控和分子后果。鉴定出 56 条途径相互作用，其中包括具有指定方向性的关键途径。还确定了由于 IPF 期间的相互作用而获得和失去的相关步骤。发现了五个关键基因的连续连接系统，与 NSIP 和结节病相比，这些基因仅在 IPF 中受到九种 miRNA 和八种转录因子的特异性调控。本研究的结果已被纳入 IPF 的综合分子和系统数据库中，以促进为这种致命疾病设计诊断和治疗解决方案。
