Lai Wanxin, Song You, Tollefsen Knut Erik, Hvidsten Torgeir R
Bioinformatics and Applied Statistics (BIAS), Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), Akershus, Norway.
Norwegian Institute for Water Research (NIVA), Oslo, Norway.
Front Genet. 2024 Dec 2;15:1508521. doi: 10.3389/fgene.2024.1508521. eCollection 2024.
An increasing number of ecotoxicological studies have used omics-data to understand the dose-response patterns of environmental stressors. However, very few have investigated complex non-monotonic dose-response patterns with multi-omics data. In the present study, we developed a novel semi-supervised network analysis workflow as an alternative to benchmark dose (BMD) modelling. We utilised a previously published multi-omics dataset generated from after chronic gamma radiation exposure to obtain novel knowledge on the dose-dependent effects of radiation. Our approach combines 1) unsupervised co-expression network analysis to group genes with similar dose responses into modules; 2) supervised classification of these modules by relevant response patterns; 3) reconstruction of regulatory networks based on transcription factor binding motifs to reveal the mechanistic underpinning of the modules; 4) differential co-expression network analysis to compare the discovered modules across two datasets with different exposure periods; and 5) pathway enrichment analysis to integrate transcriptomics and metabolomics data. Our method unveiled both known and novel effects of gamma radiation, provide insight into shifts in responses from low to high dose rates, and can be used as an alternative approach for multi-omics dose-response analysis in future. The workflow SOLA (Semi-supervised Omics Landscape Analysis) is available at https://gitlab.com/wanxin.lai/SOLA.git.
越来越多的生态毒理学研究使用组学数据来了解环境应激源的剂量反应模式。然而,很少有研究使用多组学数据来调查复杂的非单调剂量反应模式。在本研究中,我们开发了一种新颖的半监督网络分析工作流程,作为基准剂量(BMD)建模的替代方法。我们利用先前发表的多组学数据集,该数据集由慢性γ辐射暴露后生成,以获取关于辐射剂量依赖性效应的新知识。我们的方法包括:1)无监督共表达网络分析,将具有相似剂量反应的基因分组到模块中;2)通过相关反应模式对这些模块进行监督分类;3)基于转录因子结合基序重建调控网络,以揭示模块的机制基础;4)差异共表达网络分析,比较两个不同暴露期数据集之间发现的模块;5)通路富集分析,以整合转录组学和代谢组学数据。我们的方法揭示了γ辐射的已知和新效应,深入了解了从低剂量率到高剂量率反应的转变,并且可在未来用作多组学剂量反应分析的替代方法。工作流程SOLA(半监督组学景观分析)可在https://gitlab.com/wanxin.lai/SOLA.git获取。