Petrovskiy Denis V, Butkova Tatiana V, Nikolsky Kirill S, Kopylov Arthur T, Nakhod Valeriya I, Kulikova Liudmila I, Malsagova Kristina A, Kibrik Nikolai D, Rudnev Vladimir R, Izotov Alexander A, Kaysheva Anna L
Laboratory of Structural Proteomics, Institute of Biomedical Chemistry, Moscow, Russia.
Moscow Research Institute of Psychiatry - Branch of the V. Serbsky National Medical Research Centre of Psy-chiatry and Narcology of the Ministry of Health of the Russian Federation, Department of Sexology, Moscow, Russia.
Front Mol Biosci. 2024 Nov 21;11:1483933. doi: 10.3389/fmolb.2024.1483933. eCollection 2024.
The high prevalence of schizophrenia worldwide makes it necessary to proceed from subjective assessment of patient's clinical symptoms in diagnosis making to searching for circulating blood biomarkers. On the one hand, searching for molecular markers and targets for therapeutics will make it possible to refine and detail the molecular mechanisms of pathology development, while on the other hand, it will offer new opportunities for elaborating novel approaches to disease diagnosis and enhance efficacy and timeliness of drug therapy.
In this study, we performed an extended-range proteomic analysis of plasma samples collected from 48 study subjects with confirmed diagnosis of schizophrenia and 50 healthy volunteers. The high-resolution tandem mass spectra recorded in the data-dependent acquisition mode were analyzed using the MaxQuant algorithm for the library of known protein sequences and the PowerNovo algorithm for protein sequencing.
It was demonstrated that both strategies show similar results for high-abundance proteins (≥1 μg/mL). For mid-abundance (10 ng/mL - 1 μg/mL) and low-abundance (<10 ng/mL) proteins, the results obtained by the two search strategies complement each other.
Group-specific proteins for the samples of schizophrenia patients were identified, presumably being involved in synaptic plasticity, angiogenesis, transcriptional regulation, protein stabilization and degradation.
精神分裂症在全球范围内的高患病率使得在诊断过程中有必要从对患者临床症状的主观评估转向寻找循环血液生物标志物。一方面，寻找分子标记物和治疗靶点将使细化和详述病理发展的分子机制成为可能，另一方面，这将为开发疾病诊断新方法提供新机会，并提高药物治疗的疗效和及时性。
在本研究中，我们对从48名确诊为精神分裂症的研究对象和50名健康志愿者采集的血浆样本进行了扩展范围的蛋白质组学分析。使用MaxQuant算法针对已知蛋白质序列库对在数据依赖采集模式下记录的高分辨率串联质谱进行分析，并使用PowerNovo算法进行蛋白质测序。
结果表明，两种策略对高丰度蛋白质（≥1μg/mL）显示出相似的结果。对于中等丰度（10 ng/mL - 1μg/mL）和低丰度（<10 ng/mL）蛋白质，两种搜索策略获得的结果相互补充。
确定了精神分裂症患者样本中的组特异性蛋白质，推测其参与突触可塑性、血管生成、转录调控、蛋白质稳定和降解。
