scholarly journals Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk

2020 ◽  
Author(s):  
Christopher Y. Park ◽  
Jian Zhou ◽  
Aaron K. Wong ◽  
Kathleen M. Chen ◽  
Chandra L. Theesfeld ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Complex Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Full Range ◽  
Coding Region ◽  
Genome Wide ◽  
Disorder Risk

AbstractDespite the strong genetic basis of psychiatric disorders, the molecular origins of these diseases are still largely unmapped. RNA-binding proteins (RBPs) are responsible for most post-transcriptional regulation, from splicing to translational to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. Here, we leverage a deep learning approach to interrogate variant effects genome-wide, and discover that the dysregulation of RBP target sites is a principal contributor to psychiatric disorder risk. We show that specific modes of RBP regulation are genetically linked to the heritability of psychiatric disorders, and demonstrate that diverse RBP regulatory functions are reflected in distinct genome-wide negative selection signatures. Notably, RBP dysregulation has a stronger impact on psychiatric disorders than common coding region variants and explains heritability not currently captured by large-scale molecular QTL studies (expression QTLs and splicing QTLs). We share genome-wide profiles of RBP target site dysregulation, which we used to identify DDHD2 as a candidate schizophrenia risk gene, in a public web server. This resource provides a novel analytical framework to connect the full range of RNA regulation to complex disease.

scholarly journals Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk

2021 ◽  
Vol 53 (2) ◽  
pp. 166-173
Author(s):  
Christopher Y. Park ◽  
Jian Zhou ◽  
Aaron K. Wong ◽  
Kathleen M. Chen ◽  
Chandra L. Theesfeld ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Target Site ◽  
Protein Target ◽  
Genome Wide ◽  
Disorder Risk

scholarly journals Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets

2019 ◽  
Author(s):  
Minzhe Zhang ◽  
Tao Wang ◽  
Guanghua Xiao ◽  
Yang Xie
Keyword(s):  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Read Length ◽  
Circular Rnas ◽  
Binding Partners ◽  
Genome Wide ◽  
Wide Scale ◽  
And Function ◽  
Short Read Length

Circular RNAs are a special type of RNAs which recently attracted a lot of research interest in studying its formation and function. RNA binding proteins (RBPs) that bind circRNAs are important in these processes but are relatively less studied. CLIP-Seq technology has been invented and applied to profile RBP-RNA interactions on the genome-wide scale. While mRNAs are usually the focus of CLIP-Seq experiments, RBP-circRNA interactions could also be identified through specialized analysis of CLIP-Seq datasets. However, many technical difficulties are involved in this process, such as the usually short read length of CLIP-Seq reads. In this study, we created a pipeline called Clirc specialized for profiling circRNAs in CLIP-Seq data and analyzing the characteristics of RBP- circRNAs interactions. In conclusion, this is one of the first few studies to investigate circRNAs and their binding partners through repurposing CLIP-Seq datasets to our knowledge, and we hope our work will become a valuable resource for future studies into the biogenesis and function of circRNAs. Clirc software is available at https://github.com/Minzhe/Clirc

scholarly journals circVAR database: genome-wide archive of genetic variants for human circular RNAs

2020 ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background: Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results: We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research. Conclusion: We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar .

scholarly journals circVAR Database: Genome-Wide Archive of Genetic Variants for Human Circular RNAs

2020 ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background: Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results: We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research.Conclusion: We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar.

scholarly journals Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 54 ◽  
Author(s):  
Minzhe Zhang ◽  
Tao Wang ◽  
Guanghua Xiao ◽  
Yang Xie
Keyword(s):  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Read Length ◽  
Circular Rnas ◽  
Binding Partners ◽  
Genome Wide ◽  
Wide Scale ◽  
And Function ◽  
Short Read Length

Circular RNAs are a special type of RNA that has recently attracted a lot of research interest in studying its formation and function. RNA binding proteins (RBPs) that bind circRNAs are important in these processes, but have been relatively less studied. CLIP-Seq technology has been invented and applied to profile RBP-RNA interactions on the genome-wide scale. While mRNAs are usually the focus of CLIP-Seq experiments, RBP-circRNA interactions could also be identified through specialized analysis of CLIP-Seq datasets. However, many technical difficulties are involved in this process, such as the usually short read length of CLIP-Seq reads. In this study, we created a pipeline called Clirc specialized for profiling circRNAs in CLIP-Seq data and analyzing the characteristics of RBP-circRNA interactions. In conclusion, to our knowledge, this is one of the first studies to investigate circRNAs and their binding partners through repurposing CLIP-Seq datasets, and we hope our work will become a valuable resource for future studies into the biogenesis and function of circRNAs.

scholarly journals circVAR database: genome-wide archive of genetic variants for human circular RNAs

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Min Zhao ◽  
Hong Qu
Keyword(s):  
Genetic Variants ◽  
Complex Traits ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Association Studies ◽  
Chromosome 17 ◽  
Circular Rnas ◽  
Genome Wide Association Studies ◽  
Genome Wide

Abstract Background Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research. Conclusion We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar.

scholarly journals Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mariana G. Ferrarini ◽  
Avantika Lal ◽  
Rita Rebollo ◽  
Andreas J. Gruber ◽  
Andrea Guarracino ◽  
...  
Keyword(s):  
Transposable Element ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Initiation Factor ◽  
Sequence Variant ◽  
The Novel ◽  
Sequencing Data ◽  
Genome Wide ◽  
Respiratory Cells ◽  
Nuclear Ribonucleoprotein

AbstractThe novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

scholarly journals Genome-wide Identification and Expression Analysis of the YTH Domain-containing RNA-binding Protein Family in Citrus Sinensis

2019 ◽  
Vol 144 (2) ◽  
pp. 79-91 ◽  
Author(s):  
Zhigang Ouyang ◽  
Huihui Duan ◽  
Lanfang Mi ◽  
Wei Hu ◽  
Jianmei Chen ◽  
...  
Keyword(s):  
Stress Responses ◽  
Messenger Rna ◽  
Citrus Sinensis ◽  
Rna Binding ◽  
Developmental Stages ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Genome Wide ◽  
Yth Domain

In eukaryotic systems, messenger RNA regulations, including splicing, 3′-end formation, editing, localization, and translation, are achieved by different RNA-binding proteins and noncoding RNAs. The YTH domain is a newly identified RNA-binding domain that was identified by comparing its sequence with that of splicing factor YT521-B. Previous study showed that the YTH gene plays an important role in plant resistance to abiotic and biotic stress. In this study, 211 YTH genes were identified in 26 species that represent four major plant lineages. Phylogenetic analysis revealed that these genes could be divided into eight subgroups. All of the YTH genes contain a YT521 domain and have different structures. Ten YTH genes were identified in navel orange (Citrus sinensis). The expression profiles of these CitYTH genes were analyzed in different tissues and at different fruit developmental stages, and CitYTH genes displayed distinct expression patterns under heat, cold, salt, and drought stress. Furthermore, expression of the CitYTH genes in response to exogenous hormones was measured. Nuclear localization was also confirmed for five of the proteins encoded by these genes after transient expression in Nicotiana benthamiana cells. This study provides valuable information on the role of CitYTHs in the signaling pathways involved in environmental stress responses in Citrus.

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