A common molecular signature in ASD gene expression: following Root 66 to autism.
A common molecular signature in ASD gene expression: following Root 66 to autism.
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DOI：
10.1038/tp.2015.112
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发表时间：
2016-01-05
影响因子：
6.8
通讯作者：
Wall DP
中科院分区：
文献类型：
--
作者：
Diaz-Beltran L;Esteban FJ;Wall DP
已经使用血液和脑组织进行了几项关于自闭症谱系障碍的基因表达实验。个别地，这些研究促进了我们对自闭症分子病理学所涉及的分子系统的理解，并为正在进行的构建自闭症生物标志物的工作奠定了基础。在这项研究中，我们对9个独立的基因表达实验进行了综合系统生物学分析，涵盖657个自闭症，9个智力低下和发育迟缓以及566个对照样本，以确定是否存在共同的签名，并测试是否也可以在血液中检测到与自闭症相关的大脑调控模式。我们从这些实验中构建了一个差异表达基因的矩阵，并使用Jaccard系数来创建一个基于基因的同源性，通过自举验证。正如预期的那样，实验和组织类型以高统计置信度聚集在一起。然而，我们从3个不同的实验中发现了3个血液和2个大脑数据集的统计学显著亚组，这些数据集源于66个基因的高度相关的调控模式。这种Root 66似乎是非随机的，并且与自闭症具有潜在的病因学相关性，因为它们在神经过程中的丰富作用对于正常的大脑生长和功能，学习和记忆，神经变性，社会行为和认知至关重要。我们的研究结果表明，血液中存在可检测到的自闭症特征，这可能是大脑中与自闭症相关的失调的分子回声。
Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
帕金森氏病相关的G蛋白偶联受体37（GPR37/PAELR）突变与自闭症谱系障碍有关。
影响因子：
3.7
作者：
Fujita-Jimbo E;Yu ZL;Li H;Yamagata T;Mori M;Momoi T;Momoi MY
通讯作者：
Momoi MY
影响因子：
6.2
作者：
Edmonson C;Ziats MN;Rennert OM
通讯作者：
Rennert OM
人类基因表达的组织特异性的综合功能分析。
影响因子：
5.4
作者：
Dezso Z;Nikolsky Y;Sviridov E;Shi W;Serebriyskaya T;Dosymbekov D;Bugrim A;Rakhmatulin E;Brennan RJ;Guryanov A;Li K;Blake J;Samaha RR;Nikolskaya T
通讯作者：
Nikolskaya T
DOI：
10.1073/pnas.1312857110
发表时间：
2013-12-24
影响因子：
11.1
作者：
Gordon, Ilanit;Vander Wyk, Brent C.;Pelphrey, Kevin A.
通讯作者：
Pelphrey, Kevin A.