Sonis St, Antin Jh, Tedaldi Mw, Alterovitz G
Inform Genomics, Boston, MA, USA.
Oral Dis. 2013 Oct;19(7):721-7. doi: 10.1111/odi.12146. Epub 2013 Jun 28.
Approximately 40% of patients receiving conditioning chemotherapy prior to autologous hematopoietic stem cell transplants (aHSCT) develop severe oral mucositis (SOM). Aside from disabling pain, ulcerative lesions associated with SOM predispose to poor health and economic outcomes. Our objective was to develop a probabilistic graphical model in which a cluster of single-nucleotide polymorphisms (SNPs) derived from salivary DNA could be used as a tool to predict SOM risk.
Salivary DNA was extracted from 153 HSCT patients and applied to Illumina BeadChips. Using sequential data analysis, we filtered extraneous SNPs, selected loci, and identified a predictive SNP network for OM risk. We then tested the predictive validity of the network using SNP array outputs from an independent HSCT cohort.
We identified an 82-SNP Bayesian network (BN) that was related to SOM risk with a 10-fold cross-validation accuracy of 99.3% and an area under the ROC curve of 99.7%. Using samples from a small independent patient cohort (n = 16), we demonstrated the network's predictive validity with an accuracy of 81.2% in the absence of any false positives.
Our results suggest that SNP-based BN developed from saliva-sourced DNA can predict SOM risk in patients prior to aHSCT.
在接受自体造血干细胞移植(aHSCT)前接受预处理化疗的患者中,约40%会发生严重口腔黏膜炎(SOM)。除了使人丧失能力的疼痛外,与SOM相关的溃疡性病变还易导致健康状况不佳和经济负担加重。我们的目标是建立一个概率图形模型,其中源自唾液DNA的单核苷酸多态性(SNP)簇可作为预测SOM风险的工具。
从153例HSCT患者中提取唾液DNA,并应用于Illumina BeadChips。通过顺序数据分析,我们筛选了无关的SNP,选择了基因座,并确定了一个用于口腔黏膜炎风险的预测SNP网络。然后,我们使用来自一个独立HSCT队列的SNP阵列输出测试了该网络的预测有效性。
我们确定了一个与SOM风险相关的包含82个SNP的贝叶斯网络(BN),其10倍交叉验证准确率为99.3%,ROC曲线下面积为99.7%。使用来自一个小的独立患者队列(n = 16)的样本,我们证明了该网络的预测有效性,在没有任何假阳性的情况下准确率为81.2%。
我们的结果表明,从唾液来源的DNA开发的基于SNP的BN可以在aHSCT前预测患者的SOM风险。