CNA2Subpathway:识别癌症中拷贝数改变驱动的失调子通路。
CNA2Subpathway: identification of dysregulated subpathway driven by copy number alterations in cancer.
机构信息
College of Bioinformatics Science and Technology, Harbin Medical University, China.
College of Basic Medical Science, Heilongjiang University of Chinese Medicine, China.
出版信息
Brief Bioinform. 2021 Sep 2;22(5). doi: 10.1093/bib/bbaa413.
Biological pathways reflect the key cellular mechanisms that dictate disease states, drug response and altered cellular function. The local areas of pathways are defined as subpathways (SPs), whose dysfunction has been reported to be associated with the occurrence and development of cancer. With the development of high-throughput sequencing technology, identifying dysfunctional SPs by using multi-omics data has become possible. Moreover, the SPs are not isolated in the biological system but interact with each other. Here, we propose a network-based calculated method, CNA2Subpathway, to identify dysfunctional SPs is driven by somatic copy number alterations (CNAs) in cancer through integrating pathway topology information, multi-omics data and SP crosstalk. This provides a novel way of SP analysis by using the SP interactions in the system biological level. Using data sets from breast cancer and head and neck cancer, we validate the effectiveness of CNA2Subpathway in identifying cancer-relevant SPs driven by the somatic CNAs, which are also shown to be associated with cancer immune and prognosis of patients. We further compare our results with five pathway or SP analysis methods based on CNA and gene expression data without considering SP crosstalk. With these analyses, we show that CNA2Subpathway could help to uncover dysfunctional SPs underlying cancer via the use of SP crosstalk. CNA2Subpathway is developed as an R-based tool, which is freely available on GitHub (https://github.com/hanjunwei-lab/CNA2Subpathway).
生物途径反映了决定疾病状态、药物反应和细胞功能改变的关键细胞机制。途径的局部区域被定义为亚途径(SPs),其功能障碍已被报道与癌症的发生和发展有关。随着高通量测序技术的发展,利用多组学数据识别功能失调的 SPs 成为可能。此外,SPs 不是孤立存在于生物系统中,而是相互作用的。在这里,我们提出了一种基于网络的计算方法 CNA2Subpathway,通过整合途径拓扑信息、多组学数据和 SP 串扰,利用癌症中的体细胞拷贝数改变(CNAs)来识别功能失调的 SPs。这为利用系统生物学水平的 SP 相互作用进行 SP 分析提供了一种新方法。使用来自乳腺癌和头颈部癌症的数据集,我们验证了 CNA2Subpathway 识别由体细胞 CNAs 驱动的与癌症相关的 SPs 的有效性,这些 SPs 也与癌症免疫和患者预后相关。我们进一步将我们的结果与基于 CNA 和基因表达数据的五种途径或 SP 分析方法进行了比较,这些方法没有考虑 SP 串扰。通过这些分析,我们表明 CNA2Subpathway 可以通过使用 SP 串扰来帮助发现癌症中的功能失调的 SPs。CNA2Subpathway 是一个基于 R 的工具,可在 GitHub(https://github.com/hanjunwei-lab/CNA2Subpathway)上免费获得。