School of Computer Science and Technology, Xidian University, Xi'an, 710071, China.
BMC Bioinformatics. 2018 Oct 29;19(1):394. doi: 10.1186/s12859-018-2434-5.
Comprehensive analyzing multi-omics biological data in different conditions is important for understanding biological mechanism in system level. Multiple or multi-layer network model gives us a new insight into simultaneously analyzing these data, for instance, to identify conserved functional modules in multiple biological networks. However, because of the larger scale and more complicated structure of multiple networks than single network, how to accurate and efficient detect conserved functional biological modules remains a significant challenge.
Here, we propose an efficient method, named ConMod, to discover conserved functional modules in multiple biological networks. We introduce two features to characterize multiple networks, thus all networks are compressed into two feature matrices. The module detection is only performed in the feature matrices by using multi-view non-negative matrix factorization (NMF), which is independent of the number of input networks. Experimental results on both synthetic and real biological networks demonstrate that our method is promising in identifying conserved modules in multiple networks since it improves the accuracy and efficiency comparing with state-of-the-art methods. Furthermore, applying ConMod to co-expression networks of different cancers, we find cancer shared gene modules, the majority of which have significantly functional implications, such as ribosome biogenesis and immune response. In addition, analyzing on brain tissue-specific protein interaction networks, we detect conserved modules related to nervous system development, mRNA processing, etc. CONCLUSIONS: ConMod facilitates finding conserved modules in any number of networks with a low time and space complexity, thereby serve as a valuable tool for inference shared traits and biological functions of multiple biological system.
综合分析不同条件下的多组学生物学数据对于系统水平上理解生物学机制很重要。多层网络模型为我们提供了一个新的视角来同时分析这些数据,例如,在多个生物网络中识别保守的功能模块。然而,由于多个网络的规模和结构比单个网络更加复杂,如何准确有效地检测保守的功能生物学模块仍然是一个重大挑战。
在这里,我们提出了一种有效的方法,名为 ConMod,用于发现多个生物网络中的保守功能模块。我们引入了两个特征来描述多个网络,从而将所有网络压缩成两个特征矩阵。通过使用多视图非负矩阵分解(NMF)在特征矩阵中仅执行模块检测,这与输入网络的数量无关。在合成和真实生物网络上的实验结果表明,与现有方法相比,我们的方法在识别多个网络中的保守模块方面具有很大的潜力,因为它提高了准确性和效率。此外,将 ConMod 应用于不同癌症的共表达网络,我们发现了癌症共享基因模块,其中大多数都具有显著的功能意义,如核糖体生物发生和免疫反应。此外,在分析脑组织特异性蛋白质相互作用网络时,我们检测到与神经系统发育、mRNA 处理等相关的保守模块。
ConMod 可以方便地在任意数量的网络中找到保守模块,具有低时间和空间复杂度,因此是推断多个生物系统共享特征和生物学功能的有价值的工具。