Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, 120-752, Republic of Korea.
Med Biol Eng Comput. 2010 May;48(5):459-68. doi: 10.1007/s11517-010-0595-0. Epub 2010 Mar 20.
Array comparative genomic hybridization (aCGH) provides a genome-wide technique for identifying chromosomal aberrations in human diseases, including cancer. Chromosomal aberrations in cancers are defined as regions that contain an increased or decreased DNA copy number, relative to normal samples. The identification of genomic regions associated with systematic aberrations provides insights into initiation and progression of cancer, and improves diagnosis, prognosis, and therapy strategies. The McNemar test can be used to detect differentially expressed genes after discretization of gene expressions in a microarray experiment for the matched dataset. In this study, we propose a method to detect significantly altered DNA regions, shifted McNemar test, which is based on the standard McNemar test and takes into account changes in copy number variations and the region size throughout the whole genome. In addition, this novel method can be used to detect genomic regions associated with the progress of oral squamous cell carcinoma (OSCC). The performance of the proposed method was evaluated based on the homogeneity within the selected regions and the classification accuracies of the selected regions. This method might be useful for identifying new candidate genes that neighbor known genes based on the whole-genomic variation because it detects significant chromosomal regions, not independent probes.
阵列比较基因组杂交(aCGH)为识别人类疾病(包括癌症)中的染色体异常提供了一种全基因组技术。癌症中的染色体异常被定义为相对于正常样本,含有增加或减少的 DNA 拷贝数的区域。与系统异常相关的基因组区域的鉴定提供了对癌症发生和进展的深入了解,并改善了诊断、预后和治疗策略。McNemar 检验可用于在微阵列实验中对基因表达进行离散化后,检测匹配数据集的差异表达基因。在这项研究中,我们提出了一种基于标准 McNemar 检验的方法来检测显著改变的 DNA 区域,即移位 McNemar 检验,该方法考虑了整个基因组中拷贝数变异和区域大小的变化。此外,这种新方法可用于检测与口腔鳞状细胞癌(OSCC)进展相关的基因组区域。该方法的性能是基于所选区域内的同质性和所选区域的分类准确性来评估的。由于该方法检测的是显著的染色体区域,而不是独立的探针,因此它可能有助于识别基于全基因组变异的邻近已知基因的新候选基因。