PDF(Pubmed)
Abstract：
Recent advances in in-depth data-independent acquisition proteomic analysis have enabled comprehensive quantitative analysis of >10,000 proteins. Herein, an integrated proteogenomic analysis for inherited bone marrow failure syndrome (IBMFS) was performed to reveal their biological features and to develop a proteomic-based diagnostic assay in the discovery cohort; dyskeratosis congenita (n = 12), Fanconi anemia (n = 11), Diamond-Blackfan anemia (DBA, n = 9), Shwachman-Diamond syndrome (SDS, n = 6), ADH5/ALDH2 deficiency (n = 4), and other IBMFS (n = 18). Unsupervised proteomic clustering identified eight independent clusters (C1-C8), with the ribosomal pathway specifically downregulated in C1 and C2, enriched for DBA and SDS, respectively. Six patients with SDS had significantly decreased SBDS protein expression, with two of these not diagnosed by DNA sequencing alone. Four patients with ADH5/ALDH2 deficiency showed significantly reduced ADH5 protein expression. To perform a large-scale rapid IBMFS screening, targeted proteomic analysis was performed on 417 samples from patients with IBMFS-related hematological disorders (n = 390) and healthy controls (n = 27). SBDS and ADH5 protein expressions were significantly reduced in SDS and ADH5/ALDH2 deficiency, respectively. The clinical application of this first integrated proteogenomic analysis would be useful for the diagnosis and screening of IBMFS, where appropriate clinical screening tests are lacking.
摘要：
在深度独立于数据的采集蛋白质组分析方面的最新进展已经实现了对>10,000种蛋白质的全面定量分析。在这里，进行了遗传性骨髓衰竭综合征（IBMFS）的综合蛋白质基因组分析，以揭示其生物学特征，并在发现队列中开发基于蛋白质组学的诊断测定；先天性角化异常（n=12），范可尼贫血（n=11），Diamond-Blackfan贫血（DBA，n=9),Shwachman-Diamond综合征（SDS，n=6),ADH5/ALDH2缺乏症（n=4），和其他IBMFS（n=18）。无监督蛋白质组聚类确定了八个独立簇(C1-C8)，核糖体通路在C1和C2中特异性下调，富集DBA和SDS，分别。6例SDS患者SBDS蛋白表达明显下降,其中两个不是通过单独的DNA测序来诊断的。4例ADH5/ALDH2缺乏患者显示ADH5蛋白表达显著降低。为了进行大规模的快速IBMFS筛查，对来自IBMFS相关血液病患者(n=390)和健康对照(n=27)的417个样本进行靶向蛋白质组学分析.在SDS和ADH5/ALDH2缺乏症中，SBDS和ADH5蛋白表达显著降低，分别。首次整合的蛋白质基因组分析的临床应用将有助于IBMFS的诊断和筛选。在缺乏适当的临床筛查测试的地方。
