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再生障碍性贫血患者中与骨髓衰竭相关的异常代谢产物。

Abnormal metabolites related to bone marrow failure in aplastic anemia patients.

作者信息

Zhong P, Zhang J, Cui X

机构信息

Department of Rehabilitation Medicine, Jinan Military General Hospital, Jinan, China.

Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Genet Mol Res. 2015 Oct 29;14(4):13709-18. doi: 10.4238/2015.October.28.33.

Abstract

Metabolomics is the identification and quantitation of small molecules that are involved in metabolic reactions. Liquid chromatography-mass spectrometry (LC-MS) has enjoyed growing popularity as the platform for metabolomic studies due to high throughput, soft ionization, and good coverage of metabolites. Serum metabolites of aplastic anemia (AA) patients and healthy controls were investigated using LC-MS. A wavelet-based method was utilized to find and align LC-MS peaks. Principal component analysis, partial least squares discriminant analysis, and optimized potential for liquid simulations were used to identify differences in metabolite levels, and to reveal useful biomarkers. Thirty-two metabolites that were significantly altered were detected. Of these metabolites, 23 were successfully identified. In AA patients, metabolites involved amino acid biosynthesis, aminoacyl-tRNA biosynthesis, and ATP-binding cassette transporters were higher than normal, while the levels of metabolites involved in TCA cycles were lower than normal. These changes may be the primary cause or result of bone marrow failure in patients with AA.

摘要

代谢组学是对参与代谢反应的小分子进行鉴定和定量。液相色谱-质谱联用(LC-MS)作为代谢组学研究平台越来越受欢迎,这是因为它具有高通量、软电离以及对代谢物的良好覆盖性。使用LC-MS对再生障碍性贫血(AA)患者和健康对照的血清代谢物进行了研究。采用基于小波的方法来查找和对齐LC-MS峰。主成分分析、偏最小二乘判别分析以及液体模拟优化势被用于识别代谢物水平的差异,并揭示有用的生物标志物。检测到32种显著改变的代谢物。其中,23种代谢物被成功鉴定。在AA患者中,参与氨基酸生物合成、氨酰-tRNA生物合成以及ATP结合盒转运蛋白的代谢物高于正常水平,而参与三羧酸循环的代谢物水平低于正常水平。这些变化可能是AA患者骨髓衰竭的主要原因或结果。

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