Harvard Medical School, Boston, MA, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Brief Bioinform. 2023 Sep 22;24(6). doi: 10.1093/bib/bbad418.
Charting microRNA (miRNA) regulation across pathways is key to characterizing their function. Yet, no method currently exists that can quantify how miRNAs regulate multiple interconnected pathways or prioritize them for their ability to regulate coordinate transcriptional programs. Existing methods primarily infer one-to-one relationships between miRNAs and pathways using differentially expressed genes. We introduce PanomiR, an in silico framework for studying the interplay of miRNAs and disease functions. PanomiR integrates gene expression, mRNA-miRNA interactions and known biological pathways to reveal coordinated multi-pathway targeting by miRNAs. PanomiR utilizes pathway-activity profiling approaches, a pathway co-expression network and network clustering algorithms to prioritize miRNAs that target broad-scale transcriptional disease phenotypes. It directly resolves differential regulation of pathways, irrespective of their differential gene expression, and captures co-activity to establish functional pathway groupings and the miRNAs that may regulate them. PanomiR uses a systems biology approach to provide broad but precise insights into miRNA-regulated functional programs. It is available at https://bioconductor.org/packages/PanomiR.
绘制 miRNA（microRNA）在通路间的调控图谱对于描述其功能至关重要。然而，目前尚无方法能够定量评估 miRNAs 调控多个相互关联的通路的能力，或根据其协调转录程序的能力对其进行优先级排序。现有的方法主要使用差异表达基因来推断 miRNA 和通路之间的一对一关系。我们引入了 PanomiR，这是一种用于研究 miRNA 和疾病功能相互作用的计算框架。PanomiR 整合了基因表达、mRNA-miRNA 相互作用和已知的生物学通路，以揭示 miRNA 对协调多通路靶向的作用。PanomiR 利用通路活性分析方法、通路共表达网络和网络聚类算法来优先考虑靶向广泛转录疾病表型的 miRNA。它直接解决了通路的差异调控问题，而不考虑其差异基因表达，并捕捉共活性以建立功能通路分组以及可能调控它们的 miRNA。PanomiR 采用系统生物学方法提供了广泛但精确的 miRNA 调控功能程序的见解。它可在 https://bioconductor.org/packages/PanomiR 获得。
