About TargPred



This website presents variants and loci associated with traits through GWAS in the context of genomic regulatory blocks (GRBs). The aim is to provide a comprehensive view of the range of conserved synteny around a disease-associated locus that overlaps a GRB. In cases where a causative non-coding SNP within that locus is suspected to have a non-local effect (i.e., the SNP is disrupting a regulatory element affecting a gene over large genomic distances), the GRB model provides:



    

  • The range of long-range regulation (boundaries within which a shared regulatory landscape is expected, correlating roughly to a topologically-associated domain in the region)
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  • A prediction of the most likely gene(s) to be under long-range regulation within that GRB
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Below, you can find an explanation of the TargPred web resource functionality for each tab.



All SNPs Tab



This tab contains a table of SNPs for each EFO term trait in the GWAS catalog (for the EUR population)[1]. You can select the trait by scrolling or searching in the “Mapped_trait” dropdown menu. The “Inside GRB” selection allows you to limit the SNPs in the table to those found inside or outside of GRB regions.



All Loci Tab



Here you will find a similar structure for trait selection and GRB in/out filtering as in the previous tab. However, the table shows a loci-level view rather than a per-SNP view. Essentially, all SNPs for a given trait that fall within the same genomic locus (the span of which is defined by linkage disequilibrium blocks) are grouped together. The locus position for a given trait can then be used as input to view the plots in the next tab.



Locus Summary Tab



This tab contains statistical plots. Selecting a trait and locus associated with that trait will result in:



    

  • Not in GRB if the associated locus does not overlap a GRB
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  • In GRB when the associated locus overlaps a GRB
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In case a selected locus both overlaps a GRB and contains enhancers (identified from FANTOM5[2],[3] data), the following two plots will also be shown:



    

  1. A genomic locus neighbourhood plot:
Genomic locus plot
    2. 

  2. Beanplots that depict the statistical association between enhancer RNA for enhancers found in the locus and the gene transcript mRNA found in the GRB genomic neighbourhood:
Beanplot
    


    The left side (gray) of the beanplot represents the mRNA expression across FANTOM5 tissues and cell types for a given gene transcript (in this example, CCDC54 and BBX) when the enhancer in the locus is not active. The right side (purple) shows the expression levels when an enhancer in the locus is active (in this example marked as Enh1, Enh2, etc.). The asterisks mark statistically significant changes in expression levels. These plots were generated from FANTOM5[2],[3] data.
    3. 




Data Source



Currently, this app covers all EUR ancestry variants found in the NHGRI-EBI GWAS Catalog[1] downloaded in December 2022.



Genomic Regulatory Blocks



Highly conserved non-coding elements (HCNEs) delineate regions within the genome known as Genomic Regulatory Blocks (GRBs). These GRB regions exhibit a dense concentration of HCNEs, and the arrangement of local genes within them exhibits similarity even among evolutionarily distant vertebrate species[4].



For the purposes of this web resource, GRBs have been called between human (hg19) and dog (canFam396/50).



References



[1] Sollis E, et al. The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic Acids Res. 2022 Nov 9:gkac1010. doi: 10.1093/nar/gkac1010.



[2] The FANTOM Consortium and the RIKEN PMI and CLST (DGT). A promoter-level mammalian expression atlas. Nature 507, 462–470 (2014). https://doi.org/10.1038/nature13182



[3] Andersson R, et al. An atlas of active enhancers across human cell types and tissues. Nature 507, 455–461 (2014). https://doi.org/10.1038/nature12787



[4] Kikuta H, et al. Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. Genome Res. 17(5):545-555 (2007). doi: 10.1101/gr.6086307.