De novo variants (DNVs) are one of the most significant contributors to severe early-onset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Presently, a plethora of DNVs have been identified using next-generation sequencing, and many efforts have been made to understand their impact at the gene level. However, there has been little exploration of the effects at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues. Therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate a better usage and improve the isoform-level interpretation of variants, we developed NeuroPsychiatric Mutation Knowledge Base (PsyMuKB). It contains a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoform-specific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.
新生突变（De novo variants）是导致发育型神经精神疾病（如孤独症、智力障碍等）的重要因素之一。目前，高通量测序技术已鉴定出许多新生变异，并已有很多研究报道了它们在基因水平上的影响，但它们在转录本层面的影响的研究却还很少。众所周知，脑组织有着高频发生的转录本选择性剪接和调控，并比其他组织有多不同的剪接模式。因此，在转录调控水平上去探索突变将能更好地解释神经精神疾病紊乱的缘由。为了能更好地使用突变并提高其在转录本层面影响的理解，我们构建了PsyMuKB（神经精神突变知识库），一个包含多方位多层次注释的转录和翻译注释的新发突变集合，并提供能识别有组织特异性转录本的新生突变功能的知识库。PsyMuKB能灵活的搜索基因或突变，并提供对应的注释和相关内容的可视化（如基因或蛋白表达、转录本结构、蛋白质相互作用和突变位点在蛋白质结构上的映射）。PsyMuKB有一个简便的web界面，可让用户查看突变的位置和特征以及受影响基因和转录本的表达模式。总而言之，PsyMuKB是一个对于科研和临床都很有价值的资源库。可用于识别组织特异性相关的新生突变，并能方便用户对神经精神疾病进一步研究的知识库。可从http://psymukb.net免费访问PsyMuKB。





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