BACKGROUND Welding involves exposure to fumes, gases and radiant energy that can be hazardous to human health. Welding fumes (WFs) comprise a complex mixture of metallic oxides, silicates and fluorides that may result in different health effects. Inhalation of WFs in large quantities over a long periods may pose a risk of developing neurodegenerative diseases (NDGDs), but the nature of this risk is poorly understood. To address this we performed transcriptomic analysis to identify links between WF exposure and NDGDs. METHODS We developed quantitative frameworks to identify the gene expression relationships of WF exposure and NDGDs. We analyzed gene expression microarray data from fume-exposed tissues and NDGDs including Parkinson's disease (PD), Alzheimer's disease (AD), Lou Gehrig's disease (LGD), Epilepsy disease (ED) and multiple sclerosis disease (MSD) datasets. We constructed disease-gene relationship networks and identified dysregulated pathways, ontological pathways and protein-protein interaction sub-network using multilayer network topology and neighborhood-based benchmarking. RESULTS We observed that WF associated genes share 18, 16, 13, 19 and 19 differentially expressed genes with PD, AD, LGD, ED and MSD respectively. Gene expression dysregulation along with relationship networks, pathways and ontologic analysis indicate that WFs may be linked to the progression of these NDGDs. CONCLUSIONS Our developed network-based approach to analysis and investigate the genetic effects of welding fumes on PD, AD, LGD, ED and MSD neurodegenerative diseases could be helpful to understand the causal influences of WF exposure for the progression of the NDGDs.

中文翻译：

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焊接烟雾对神经退行性疾病进展的遗传影响。

背景技术焊接涉及暴露于对人体健康有害的烟气，气体和辐射能。焊接烟气（WFs）包含金属氧化物，硅酸盐和氟化物的复杂混合物，可能导致不同的健康影响。长期大量吸入WFs可能会导致发生神经退行性疾病（NDGDs）的风险，但这种风险的性质了解甚少。为了解决这个问题，我们进行了转录组分析，以识别白粉病暴露和NDGDs之间的联系。方法我们开发了定量框架以鉴定WF暴露和NDGDs的基因表达关系。我们分析了来自烟气暴露组织和NDGD的基因表达微阵列数据，包括帕金森氏病（PD），阿尔茨海默氏病（AD），卢格里格氏病（LGD），癫痫病（ED）和多发性硬化症（MSD）数据集。我们构建了疾病-基因关系网络，并使用多层网络拓扑和基于邻域的基准测试确定了失调的途径，本体论途径和蛋白质-蛋白质相互作用子网络。结果我们观察到WF相关基因分别与PD，AD，LGD，ED和MSD共享18、16、13、19和19个差异表达的基因。基因表达失调以及关系网络，途径和本体分析表明，WF可能与这些NDGD的进展有关。结论我们开发了基于网络的方法来分析和研究焊接烟尘对PD，AD，LGD，