3DSNP: a database for linking human noncoding SNPs to their three-dimensional interacting genes

Abstract

The vast noncoding portion of the human genome harbors a rich array of functional elements and disease-causing regulatory variants. Recent high-throughput chromosome conformation capture studies have outlined the principles of these elements interacting and regulating the expression of distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements. 3DSNP integrates 3D chromatin interactions, local chromatin signatures in different cell types and linkage disequilibrium (LD) information from the 1000 Genomes Project. 3DSNP provides informative visualization tools to display the integrated local and 3D chromatin signatures and the genetic associations among variants. Data from different functional categories are integrated in a scoring system that quantitatively measures the functionality of SNPs to help select important variants from a large pool. 3DSNP is a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes. The 3DSNP database is available at http://biotech.bmi.ac.cn/3dsnp/.

Figure 1.

The data sources of 3DSNP (see the description of data collection and processing for details).

Figure 2.

The regional LD plot of associated SNPs of rs12740374. In the plot, x-axis shows chromosome coordinates, y-axis shows values for r², the size of the node represents its total score, and associated SNPs in five populations (AFR: African, AMR: Ad Mixed American, ASN: East Asian, EUR: European and SAS: South Asian) are displayed in different colors, and rs12740374 is displayed in black.

Figure 3.

The circular plot (A) and linear plot (B) of chromosome interactions and epigenetic signatures in HepG2 cells related to rs12740374. In the circular plot, from outer to inner, the circle represents chromatin states, annotated genes, histone modification set (red), transcription factor set (blue), current SNP and associated SNPs, and 3D chromatin interactions, respectively. The three circles in the histone modification set are H3K4me1, H3K4me3, H3K27ac, and the three circles in the TFs set are CTCF, CEBPB and CEBPD. In the linear plot, from top to bottom, the tracks are: genomic coordinates, chromatin interactions, current SNP, UCSC genes, RefSeq genes, histone modifications, CTCF binding sites, DNase Clusters and mammal conservation.