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Integrated Transcriptome Analyses Revealed Key Target Genes in Mouse Models of Autism.
Autism Research ( IF 4.7 ) Pub Date : 2019-11-19 , DOI: 10.1002/aur.2240
Weicheng Duan 1 , Kang Wang 1 , Yijie Duan 1 , Xufeng Chu 1 , Ruoyun Ma 2 , Ping Hu 3 , Bo Xiong 1
Affiliation  

Genetic mutations are the major pathogenic factor of Autism Spectrum Disorder (ASD). In recent years, more and more ASD risk genes have been revealed, among which there are a group of transcriptional regulators. Considering the similarity of the core clinical phenotypes, it is possible that these different factors may regulate the expression levels of certain key targets. Identification of these targets could facilitate the understanding of the etiology and developing of novel diagnostic and therapeutic methods. Therefore, we performed integrated transcriptome analyses of RNA‐Seq and microarray data in multiple ASD mouse models and identified a number of common downstream genes in various brain regions, many of which are related to the structure and function of the synapse components or drug addiction. We then established protein–protein interaction networks of the overlapped targets and isolated the hub genes by 11 algorithms based on the topological structure of the networks, including Sdc4, Vegfa, and Cp in the Cortex‐Adult subgroup, Gria1 in the Cortex‐Juvenile subgroup, and Kdr, S1pr1, Ubc, Grm2, Grin2b, Nrxn1, Pdyn, Grin3a, Itgam, Grin2a, Gabra2, and Camk4 in the Hippocampus‐Adult subgroup, many of which have been associated with ASD in previous studies. Finally, we cross compared our results with human brain transcriptional data sets and verified several key candidates, which may play important role in the pathology process of ASD, including SDC4, CP, S1PR1, UBC, PDYN, GRIN2A, GABRA2, and CAMK4. In summary, by integrated bioinformatics analysis, we have identified a series of potentially important molecules for future ASD research. Autism Res 2020, 13: 352–368. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

中文翻译:

整合转录组分析自闭症小鼠模型中揭示的关键目标基因。

遗传突变是自闭症谱系障碍(ASD)的主要致病因素。近年来,越来越多的ASD风险基因被发现,其中有一组转录调节因子。考虑到核心临床表型的相似性,这些不同因素可能会调节某些关键靶标的表达水平。这些靶标的鉴定可以促进对病因的理解和新的诊断和治疗方法的开发。因此,我们在多个ASD小鼠模型中进行了RNA-Seq和微阵列数据的整合转录组分析,并确定了大脑各个区域的许多常见下游基因,其中许多与突触成分的结构和功能或药物成瘾有关。SDC4VEGFA的Cp在Cortex-成人群,GRIA1在Cortex-少年群,和KDRS1pr1UBCGRM2GRIN2BNRXN1PDYNGRIN3AITGAMGrin2aGABRA2CAMK4在海马—成人亚组中,许多在先前的研究中都与自闭症相关。最后,我们将我们的结果与人脑转录数据集进行了交叉比较,并验证了几个关键候选物,这些候选物可能在ASD的病理过程中起重要作用,包括SDC4CPS1PR1UBCPDYNGRIN2AGABRA2CAMK4。总之,通过综合的生物信息学分析,我们确定了一系列潜在的重要分子,可用于未来的ASD研究。Autism Res 2020,13:352-368。©2019国际自闭症研究会,Wiley Periodicals,Inc.
更新日期:2019-11-19
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