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一项结合液相色谱-质谱联用/核磁共振代谢组学和转录组学用于精神分裂症精确诊断的综合病理学研究。

An integrated pathological research for precise diagnosis of schizophrenia combining LC-MS/H NMR metabolomics and transcriptomics.

作者信息

Wang Tianyang, Li Ping, Meng Xiangyu, Zhang Jinling, Liu Qi, Jia Cuicui, Meng Nana, Zhu Kunjie, Lv Dan, Sun Lei, Shang Tinghuizi, Lin Yan, Niu Weipan, Lin Song

机构信息

School of Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang Province 161006, China.

School of Mental Health, Qiqihar Medical University, Qiqihar, Heilongjiang Province 161006, China.

出版信息

Clin Chim Acta. 2022 Jan 1;524:84-95. doi: 10.1016/j.cca.2021.11.028. Epub 2021 Dec 1.

DOI:10.1016/j.cca.2021.11.028
PMID:34863699
Abstract

BACKGROUND

Lack of clinically specific biomarkers has impeded the precise diagnosis of schizophrenia, meanwhile, limited comprehending of pathogenesis for schizophrenia has restricted the effective treatment.

METHOD

An integrated multi-omic approach, combining metabolomic platform (LC-MS and H NMR) and transcriptomic platform, was established to differentiate healthy subjects from schizophrenia patients. Based on filtered metabolites and genes, characteristic spectrums were further built. Then, representative metabolites and genes were screened out through Boruta algorithm. Moreover, characteristic diagnostic formulas were established via LASSO regression analysis.

RESULT

As a result, 86 differential metabolites (in line with amino acid metabolism, etc.) and 189 differential expression genes (involving in amino acid metabolic process, etc.) were obtained as potential biomarkers for schizophrenia. The latent interaction between metabolites with genes, such as HMGCLL1 with energy metabolism, etc., was further studied through the analysis of pathway-based integration. Moreover, fine predictive ability was attributed to characteristic metabolomic/transcriptomic diagnostic spectrums/formulas.

CONCLUSION

The functional relationships of filtered metabolites and genes were studied, which could elaborate the pathological process of schizophrenia more systemically, supplying more precise information on mechanism description and diagnostic evidence of schizophrenia.

摘要

背景

缺乏临床特异性生物标志物阻碍了精神分裂症的精确诊断,同时,对精神分裂症发病机制的有限理解限制了有效治疗。

方法

建立了一种整合的多组学方法,结合代谢组学平台(液相色谱-质谱联用和核磁共振氢谱)和转录组学平台,以区分健康受试者和精神分裂症患者。基于筛选出的代谢物和基因,进一步构建特征谱。然后,通过Boruta算法筛选出代表性代谢物和基因。此外,通过套索回归分析建立特征诊断公式。

结果

结果获得了86种差异代谢物(与氨基酸代谢等相关)和189个差异表达基因(涉及氨基酸代谢过程等)作为精神分裂症的潜在生物标志物。通过基于通路的整合分析,进一步研究了代谢物与基因之间的潜在相互作用,如HMGCLL1与能量代谢等之间的相互作用。此外,特征代谢组学/转录组学诊断谱/公式具有良好的预测能力。

结论

研究了筛选出的代谢物与基因的功能关系,能够更系统地阐述精神分裂症的病理过程,为精神分裂症的机制描述和诊断证据提供更精确的信息。

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