Table_1_Multi-Omics Analysis of Acute Lymphoblastic Leukemia Identified the Methylation and Expression Differences Between BCP-ALL and T-ALL.XLSX

Acute lymphoblastic leukemia (ALL) as a common cancer is a heterogeneous disease which is mainly divided into BCP-ALL and T-ALL, accounting for 80–85% and 15–20%, respectively. There are many differences between BCP-ALL and T-ALL, including prognosis, treatment, drug screening, gene research and so on. In this study, starting with methylation and gene expression data, we analyzed the molecular differences between BCP-ALL and T-ALL and identified the multi-omics signatures using Boruta and Monte Carlo feature selection methods. There were 7 expression signature genes (CD3D, VPREB3, HLA-DRA, PAX5, BLNK, GALNT6, SLC4A8) and 168 methylation sites corresponding to 175 methylation signature genes. The overall accuracy, accuracy of BCP-ALL, accuracy of T-ALL of the RIPPER (Repeated Incremental Pruning to Produce Error Reduction) classifier using these signatures evaluated with 10-fold cross validation repeated 3 times were 0.973, 0.990, and 0.933, respectively. Two overlapped genes between 175 methylation signature genes and 7 expression signature genes were CD3D and VPREB3. The network analysis of the methylation and expression signature genes suggested that their common gene, CD3D, was not only different on both methylation and expression levels, but also played a key regulatory role as hub on the network. Our results provided insights of understanding the underlying molecular mechanisms of ALL and facilitated more precision diagnosis and treatment of ALL.

急性淋巴细胞白血病（Acute Lymphoblastic Leukemia, ALL）作为一类常见恶性肿瘤，属于异质性疾病，主要分为B细胞系急性淋巴细胞白血病（BCP-ALL）与T细胞系急性淋巴细胞白血病（T-ALL）两个亚型，二者占比分别为80%~85%与15%~20%。BCP-ALL与T-ALL在预后、治疗方案、药物筛选及基因研究等多个维度均存在显著差异。本研究以甲基化数据与基因表达数据为基础，分析了BCP-ALL与T-ALL的分子差异，并通过Boruta算法与蒙特卡洛特征选择方法，筛选得到多组学特征标志物。本次分析共获得7个表达特征基因（CD3D、VPREB3、HLA-DRA、PAX5、BLNK、GALNT6、SLC4A8），以及对应175个甲基化特征基因的168个甲基化位点。采用上述特征标志物构建的重复增量修剪以产生误差减少（RIPPER）分类器，经3次重复10折交叉验证评估后，其整体准确率、BCP-ALL分类准确率与T-ALL分类准确率分别为0.973、0.990与0.933。在175个甲基化特征基因与7个表达特征基因中，共有2个重叠基因，即CD3D与VPREB3。对甲基化与表达特征基因开展调控网络分析后发现，二者的共同基因CD3D不仅在甲基化与表达水平上均存在显著差异，还作为枢纽基因在调控网络中发挥关键调控作用。本研究结果为解析急性淋巴细胞白血病的潜在分子机制提供了新的视角，同时可为该病的精准诊疗提供理论支撑。