Politano Gianfranco, Orso Francesca, Raimo Monica, Benso Alfredo, Savino Alessandro, Taverna Daniela, Di Carlo Stefano
Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, Italy.
Molecular Biotechnology Center (MBC), Via Nizza, 52, Torino, 10126, Italy.
BMC Bioinformatics. 2016 Apr 8;17:157. doi: 10.1186/s12859-016-0964-2.
Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing snapshots of the overall cell dynamics. Most of the attempts to reconstruct signal transduction pathways are limited to single regulator networks including only genes/proteins. However, networks involving a single type of regulator and neglecting transcriptional and post-transcriptional regulations mediated by transcription factors and microRNAs, respectively, may not fully reveal the complex regulatory mechanisms of a cell. We observed a lack of computational instruments supporting explorative analysis on this type of three-component signal transduction pathways.
We have developed CyTRANSFINDER, a new Cytoscape plugin able to infer three-component signal transduction pathways based on user defined regulatory patterns and including miRNAs, TFs and genes. Since CyTRANSFINDER has been designed to support exploratory analysis, it does not rely on expression data. To show the potential of the plugin we have applied it in a study of two miRNAs that are particularly relevant in human melanoma progression, miR-146a and miR-214.
CyTRANSFINDER supports the reconstruction of small signal transduction pathways among groups of genes. Results obtained from its use in a real case study have been analyzed and validated through both literature data and preliminary wet-lab experiments, showing the potential of this tool when performing exploratory analysis.
生物学研究越来越依赖网络模型来研究复杂现象。信号转导通路是分子回路，它模拟细胞如何接收、处理和响应来自环境的信息，提供了整体细胞动态的快照。大多数重建信号转导通路的尝试都局限于仅包括基因/蛋白质的单一调节因子网络。然而，仅涉及单一类型调节因子且分别忽略由转录因子和微小RNA介导的转录和转录后调控的网络，可能无法完全揭示细胞的复杂调控机制。我们发现缺乏支持对这类三组分信号转导通路进行探索性分析的计算工具。
我们开发了CyTRANSFINDER，这是一种新的Cytoscape插件，能够根据用户定义的调控模式推断包括微小RNA、转录因子和基因的三组分信号转导通路。由于CyTRANSFINDER旨在支持探索性分析，它不依赖于表达数据。为了展示该插件的潜力，我们将其应用于一项对在人类黑色素瘤进展中特别相关的两种微小RNA，即miR - 146a和miR - 214的研究中。
CyTRANSFINDER支持在基因组之间重建小的信号转导通路。通过文献数据和初步的湿实验室实验对其在实际案例研究中获得的结果进行了分析和验证，显示了该工具在进行探索性分析时的潜力。
