基于网络引导随机森林的电离辐射对人类B细胞影响机制
doi: 10.11728/cjss2025.02.2024-0055 cstr: 32142.14.cjss.2024-0055
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何敏敏 女, 1998年12月出生于山西省运城市, 毕业于华中农业大学信息学院生物信息系. 主要研究方向为空间疾病致病机制解析、药物发现等. E-mail: 1173505363@qq.com -
朱玉锋 男, 2001年11月出生于江苏省泰州市, 毕业于华中农业大学信息学院生物信息系. 主要研究方向为空间生物医学、药物筛选等. E-mail: neverbo1101@outlook.com -
全源 女, 1990年7月出生于广西壮族自治区柳州市, 现为华中农业大学信息学院副研究员, 博士生导师, 主要研究方向为空间生物信息学、空间医学、药物发现等. E-mail: quanyuan@mail.hzau.edu.cn
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通讯作者:
Mechanism of the Effect of Ionizing Radiation on Human B Cells Based on Network-guided Random Forest
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摘要: 在空间环境中, 电离辐射可破坏细胞DNA和其他分子结构, 导致细胞突变或死亡, 增加癌症及其他疾病风险. 解析电离辐射对人类细胞的影响机制已成为航天医学领域亟待解决的问题. 近年来, 空间组学数据的大量累计以及生物信息学技术的发展为该问题的解决提供了可行途径. 本文使用网络引导随机森林(Network Guided Random Forest, NGF)算法研究人类B细胞对电离辐射的响应机制. 基于基因功能富集分析发现人类B细胞在经过大剂量电离辐射后难以对受损伤的DNA进行正常修复, 大量细胞发生凋亡或癌变. 基于cMap(Connectivity Map)数据库进行潜在抗电离辐射药物筛选, 结果显示紫杉醇和醉椒素等天然产物或可辅助人体抵抗电离辐射伤害. 研究结果将为空间环境对人体影响机制的解析奠定基础, 辅助开展航天员抗空间逆境策略研究.
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关键词:
- 电离辐射 /
- 人类B细胞 /
- 网络引导随机森林算法 /
- 基因功能分析 /
- 药物筛选
Abstract: With the intensification of the problems of the Earth’s population, energy and ecological environment, space immigration may become a feasible solution. In the space environment, ionizing radiation will damage the DNA and other molecular structures of human cells, causing cell mutation or death, increasing the risk of cancer and other diseases. The mechanism of the effect of ionizing radiation on human cells has become an urgent problem in the field of space medicine. In recent years, a large amount of spatial omics data has accumulated, and the development of bioinformatics technology provides a feasible way to solve the above problems. In this study, the Network Guided Random Forest (NGF) algorithm was used to investigate the response mechanism of human B cells to ionizing radiation. Based on gene function enrichment analysis, it was found that human B cells could not repair the damaged DNA normally after high dose of ionizing radiation, and a large number of cells suffered apoptosis or cancer. In addition, screening of potential anti-ionizing radiation drugs based on the cMap (Connectivity Map) database showed that natural products such as paclitaxel and zonicin may assist the human body in resisting ionizing radiation damage. This paper will lay a foundation for the analysis of the influence mechanism of space environment on human beings, and help astronauts to study the strategies of resisting space adversity. -
图 1 基于差异表达分析和NGF算法研究人B细胞 对电离辐射响应机制的方法流程
Figure 1. Flow chart of the method to study the response mechanism of human B cells to ionizing radiation based on differential expression analysis and network-guided random forest algorithm
图 2 10 Gy电离辐射后2 h (a)和6 h (b) NGF重要性打分前100的基因差异可视化处理
Figure 2. Volcano plot of gene differential expression in the top 100 NGF importance scores 2 h (a) and 6 h (b) after 10 Gy ionizing radiation
图 3 10 Gy电离辐射2 h后的GO分析(a)和KEGG分析(b)
Figure 3. GO (a) and KEGG (b) analysis after 2 hours of 10 Gy ionizing radiation
图 4 10 Gy电离辐射6 h后的GO分析(a)和KEGG分析(b)
Figure 4. GO (a) and KEGG (b) analysis after 6 hours of 10 Gy ionizing radiation
表 1 电离辐射响应重要基因起源分析
Table 1. Analysis of the origin of important genes in response to ionizing radiation
基因起源阶段 基因数 P-value Cellular_organisms 35 0.0424 Euk_Archaea 8 0.308 Euk+Bac 60 0.0101 Eukaryota 229 0.000000819 Eumetazoa 129 0.0949 Mammalia 30 1.00 Opisthokonta 30 0.0716 Vertebrata 48 1.00 
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表 2 基于cMap数据库筛选的抗辐射药物
Table 2. Anti-radiation drugs screened based on cMap database
药物名称 P-value 药物疗效 紫杉醇 0.00177 通过抑制微管网络的形成, 抑制肿瘤细胞增殖分裂 阿苯达唑 0.00004 通过与蠕虫β–微管蛋白结合, 抑制其聚合或组装成微管 利美索龙 0.00275 糖皮质激素受体激动剂治疗眼部炎症 氯倍他索 0.00559 治疗硬皮病 普萘洛尔 0.00641 肾上腺素受体拮抗剂, 治疗心律失常 醉椒素 0.00703 抗惊厥, 治疗肌肉松弛
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表 3 基于cMap数据库筛选的辐射增敏剂
Table 3. Radiation sensitizers screened based on cMap database
药物名称 P-value 药物疗效 莫诺苯宗 0 治疗黑色素沉积 盐酸苯氧苄胺 0 治疗高血压和嗜铬细胞瘤 依米丁 0 抑制蛋白质合成 海恩酮 0 DNA合成抑制剂, 抗血吸虫 依托泊苷 0 细胞周期特异性抗肿瘤药物, 作用于DNA拓扑异构酶Ⅱ 三氟胸苷 0 可在DNA复制过程中使用, 阻止碱基对形成 白藜芦醇 0 抗氧化、抗炎、抗癌及心血管保护等 伊利替康 0.00008 由喜树碱制成, 可导致DNA损伤 甲氨蝶呤 0.00012 抗叶酸类抗肿瘤药 毒胡萝卜素 0.00172 诱导内质网应激反应性细胞凋亡 洛莫司汀 0.00422 烷化剂类抗肿瘤药, 使DNA链断裂, 可通过血脑屏障
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