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基于生物信息学的非靶向代谢组学分析用于甲基苯丙胺滥用的临床筛查

Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse.

作者信息

Kesmen Elif, Asliyüksek Hızır, Kök Ahmet Nezih, Şenol Cem, Özli Semih, Senol Onur

机构信息

Ataturk University, Erzurum, Turkey.

出版信息

Forensic Toxicol. 2025 Jan;43(1):117-129. doi: 10.1007/s11419-024-00703-2. Epub 2024 Sep 18.

DOI:10.1007/s11419-024-00703-2
PMID:39292360
Abstract

PURPOSE

Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach.

METHODS

38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument.

RESULTS

Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body.

CONCLUSION

It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.

摘要

目的

苯丙胺类兴奋剂非常常见,其使用在全球正成为一个非常严重的社会问题。成千上万的成瘾者面临包括精神、代谢、行为和神经紊乱在内的多种健康问题。除此之外,还有几份报告指出成瘾者实施犯罪案件的倾向风险有所增加。因此,甲基苯丙胺成瘾不仅是一个个人健康问题,也是一个社会问题。在我们的研究中,我们旨在通过非靶向代谢组学方法研究甲基苯丙胺长期使用的发病机制。

方法

仔细收集38份血浆样本并进行提取,用于非靶向代谢组学分析。进行液液萃取以从样本中获取尽可能多的代谢物。萃取过程完成后,将样本转移至小瓶中,并通过飞行时间质谱仪进行评估。

结果

通过两组之间的倍数分析和韦尔奇检验,显著鉴定出了代谢物的改变。根据数据依赖采集方法注释了42种不同的化合物。还进行了通路分析,以了解甲基苯丙胺对人体的有害影响。

结论

据报道,药物暴露可能会影响氨基酸、脂肪、能量代谢和维生素的多种代谢途径。还开发并验证了一种替代生物信息学模型,以预测任何刑事案件中的慢性甲基苯丙胺吸毒者。该生成的模型通过了ROC曲线分析和置换检验,并通过评估两组之间的代谢改变正确地对对照组和吸毒者进行了分类。

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