Chen Yongxin, Oh Jung Hun, Sandhu Romeil, Lee Sangkyu, Deasy Joseph O, Tannenbaum Allen
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, NY, USA.
Department of Biomedical Informatics, Stony Brook University, NY, USA.
Proceedings (IEEE Int Conf Bioinformatics Biomed). 2016 Dec;2016:1302-1306. doi: 10.1109/BIBM.2016.7822706. Epub 2017 Jan 19.
More than half of all cancer patients receive radiotherapy in their treatment process. However, our understanding of abnormal transcriptional responses to radiation remains poor. In this study, we employ an extended definition of Ollivier-Ricci curvature based on LI-Wasserstein distance to investigate genes and biological processes associated with ionizing radiation (IR) and ultraviolet radiation (UV) exposure using a microarray dataset. Gene expression levels were modeled on a gene interaction topology downloaded from the Human Protein Reference Database (HPRD). This was performed for IR, UV, and mock datasets, separately. The difference curvature value between IR and mock graphs (also between UV and mock) for each gene was used as a metric to estimate the extent to which the gene responds to radiation. We found that in comparison of the top 200 genes identified from IR and UV graphs, about 20~30% genes were overlapping. Through gene ontology enrichment analysis, we found that the metabolic-related biological process was highly associated with both IR and UV radiation exposure.
超过一半的癌症患者在治疗过程中接受放射治疗。然而,我们对辐射异常转录反应的了解仍然很少。在本研究中,我们基于LI-瓦瑟斯坦距离采用扩展的奥利维耶-里奇曲率定义,使用微阵列数据集研究与电离辐射(IR)和紫外线辐射(UV)暴露相关的基因和生物学过程。基因表达水平是根据从人类蛋白质参考数据库(HPRD)下载的基因相互作用拓扑结构进行建模的。分别对IR、UV和模拟数据集进行此操作。每个基因的IR图与模拟图(UV图与模拟图之间也是如此)之间的差异曲率值用作衡量该基因对辐射反应程度的指标。我们发现,在比较从IR图和UV图中鉴定出的前200个基因时,约20%至30%的基因是重叠的。通过基因本体富集分析,我们发现代谢相关的生物学过程与IR和UV辐射暴露均高度相关。