Danish Headache Center, Department of Neurology, Copenhagen University Hospital, 2600, Glostrup, Denmark.
Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
BMC Genomics. 2022 Nov 19;23(1):759. doi: 10.1186/s12864-022-08981-z.
The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. We hypothesize, that performing multi-omic analyses during CPT gives the opportunity to home in on molecular mechanisms involved. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken. RNA-Sequencing, steroid profiling and untargeted metabolomics were performed. Each 'omic level was analyzed separately at both single-feature and systems-level (principal component [PCA] and partial least squares [PLS] regression analysis) and all 'omic levels were combined using an integrative multi-omics approach, all using the paired-sample design.
We showed that PCA was not able to discriminate time points, while PLS did significantly distinguish time points using metabolomics and/or transcriptomic data, but not using conventional physiological measures. Transcriptomic and metabolomic data revealed at feature-, systems- and integrative- level biologically relevant processes involved during CPT, e.g. lipid metabolism and stress response.
Multi-omics strategies have a great potential in pain research, both at feature- and systems- level. Therefore, they should be exploited in intervention studies, such as pain provocation tests, to gain knowledge on the biological mechanisms involved in complex traits.
冷加压试验(CPT)是一种广泛用于研究疼痛耐受和心血管反应的疼痛诱发试验。我们假设,在 CPT 期间进行多组学分析有机会深入研究涉及的分子机制。22 名女性在 CPT 前后进行了表型评估,并采集了血液样本。进行了 RNA 测序、类固醇分析和非靶向代谢组学分析。在单个特征和系统水平(主成分[PCA]和偏最小二乘[PLS]回归分析)上分别分析每个“组学”水平,并使用整合的多组学方法结合所有“组学”水平,所有方法均使用配对样本设计。
我们表明 PCA 无法区分时间点,而 PLS 确实使用代谢组学和/或转录组学数据显著区分了时间点,但不使用常规生理测量。转录组学和代谢组学数据在特征、系统和整合水平上揭示了 CPT 过程中涉及的生物学相关过程,例如脂质代谢和应激反应。
多组学策略在疼痛研究中具有很大的潜力,无论是在特征水平还是系统水平。因此,它们应该在干预研究中得到利用,例如疼痛诱发试验,以了解涉及复杂特征的生物学机制。