Construction Of De Novo Variants Knowledge Base For Psychiatric Disorders

Psychiatric disorders are the common diseases characterized by high prevalence,high recurrence and high disability rates,which frequently bring health and economic burdens.Among the numerous causes of psychiatric disorders,de novo variants(DNVs)are one of the most critical factors leading to severe psychiatric disorders.Research on how DNVs affect the occurrence and development of psychiatric disorders has always been a hot topic.At present,tremendous DNVs have been identified by next-generation sequencing technology,and numerous scientists have conducted related research to under these variants at gene level.However,little is known about the effect of DNVs at mRNA isoform(also known as transcript)level.Brain tissues involves the frequently occurring alternative splicing regulation,and there are more splicing modes than other tissues.Once pre-RNA is subjected to the interaction of spliceosome with splicing factor,it will produce multiple mature mRNA isoforms with various functions.Therefore,it is essential to explore the impact of DNVs at mRNA isoform level,so as to better explain the underlying mechanism of psychiatric disorders.This study carried out accurate annotations based on the manually collected DNVs data reported in literature,and integrated the large-scale omics data.Finally,the psychiatric disorder DNVs knowledge base PsyMuKB was constructed,which contained a set of DNVs with comprehensive interpretations of transcription and translation annotations and might be used to identify the alternative splicing transcript-specific mutations.PsyMuKB allowed to flexibly search for genes or mutations,and provided information description about the mutated gene as well as related visualization effect,such as gene expression,transcript genome structure,protein interactions,and mutation site information mapped on the protein structure.Furthermore,PsyMuKB also offered an easy-to-use web interface,which allowed the users to promptly preview the mutation location and characteristics,together with the expression patterns of affected genes and alternative splicing transcripts.In summary,the psychiatric disorder DNVs knowledge base developed in this paper is an integrated resource platform to explore DNVs at multiple levels,which can be used to identify the tissue specificity-related mutations,and further investigate the disease-related molecular pathways and pathogenesis.The current version can be freely accessible at http://psymukb.com.