Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome.
Convergent cerebrospinal fluid proteomes and metabolic ontologies in humans and animal models of Rett syndrome.
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DOI：
10.1016/j.isci.2022.104966
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发表时间：
2022-09-16
期刊：
影响因子：
5.8
通讯作者：
Faundez, Victor
中科院分区：
文献类型：
--
作者：
Zlatic, Stephanie A.;Duong, Duc;Gadalla, Kamal K. E.;Murage, Brenda;Ping, Lingyan;Shah, Ruth;Fink, James J.;Khwaja, Omar;Swanson, Lindsay C.;Sahin, Mustafa;Rayaprolu, Sruti;Kumar, Prateek;Rangaraju, Srikant;Bird, Adrian;Tarquinio, Daniel;Carpenter, Randall;Cobb, Stuart;Faundez, Victor
MECP 2功能丧失突变导致Rett综合征，这是一种由脑转录组破坏引起的神经发育障碍。这些转录缺陷如何被解码成疾病蛋白质组仍然是未知的。我们研究了Rett脑脊液（CSF）的蛋白质组，以确定共识Rett蛋白质组和三个物种之间共享的本体。Rett CSF蛋白质组富集了注释为HDL脂蛋白、补体、线粒体、柠檬酸/丙酮酸代谢、突触隔室和神经分泌蛋白VGF的蛋白质。我们使用共享的Rett本体来选择用于正交定量和功能验证的分析物。VGF和本体选择的CSF蛋白质具有基因型辨别能力，如通过Mecp 2-/y和Mecp 2-/+中的受试者操作特征分析所确定的。差异表达的CSF蛋白将Rett与相关的神经发育障碍CDKL 5缺乏症区分开来。我们建议Mecp 2突变CSF蛋白质组和本体论告知疾病的推定机制和生物标志物。我们认为Rett综合征是突触和代谢功能障碍的结果。跨物种和实验方法共享的Rett CSF蛋白质组本体Rett CSF蛋白质组富集HDL脂蛋白、线粒体和突触本体VGF水平将Mecp 2-/y、Mecp 2-/+与对照CSF区分Rett CSF蛋白质组和本体与Cdkl 5-/y CSF疾病中的那些不同;病理生理学;临床神经科学;蛋白质组学
MECP2 loss-of-function mutations cause Rett syndrome, a neurodevelopmental disorder resulting from a disrupted brain transcriptome. How these transcriptional defects are decoded into a disease proteome remains unknown. We studied the proteome of Rett cerebrospinal fluid (CSF) to identify consensus Rett proteome and ontologies shared across three species. Rett CSF proteomes enriched proteins annotated to HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments, and the neurosecretory protein VGF. We used shared Rett ontologies to select analytes for orthogonal quantification and functional validation. VGF and ontologically selected CSF proteins had genotypic discriminatory capacity as determined by receiver operating characteristic analysis in Mecp2-/y and Mecp2−/+. Differentially expressed CSF proteins distinguished Rett from a related neurodevelopmental disorder, CDKL5 deficiency disorder. We propose that Mecp2 mutant CSF proteomes and ontologies inform putative mechanisms and biomarkers of disease. We suggest that Rett syndrome results from synapse and metabolism dysfunction. Shared Rett CSF proteome ontologies across species and experimental approaches Rett CSF proteome enriches HDL lipoprotein, mitochondria, and synapse ontologies VGF levels discriminate Mecp2-/y, Mecp2−/+, from control CSF Rett CSF proteome and ontologies are distinct from those in Cdkl5-/y CSF Disease; Pathophysiology; Clinical neuroscience; Proteomics
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影响因子：
11.8
作者：
Chau KF;Springel MW;Broadbelt KG;Park HY;Topal S;Lun MP;Mullan H;Maynard T;Steen H;LaMantia AS;Lehtinen MK
通讯作者：
Lehtinen MK
影响因子：
14.5
作者：
Banerjee, Abhishek;Miller, Meghan T.;Kaufmann, Walter E.
通讯作者：
Kaufmann, Walter E.
影响因子：
11.8
作者：
Cheng, Tian-Lin;Wang, Zhizhi;Qiu, Zilong
通讯作者：
Qiu, Zilong
影响因子：
1.7
作者：
BUDDEN, SS;MYER, EC;BUTLER, IJ
通讯作者：
BUTLER, IJ
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J