Data content

I. Data summary

rVarBase includes regulatory feature annotations of known and novel human variants. Variants' regulatory features were annotated with: chromatin state of the region surrounding variant, regulatory elements overlapped with variant and variant's potential target genes. It also provides optioned extended annotation for variants and traits associated with variant. The data for rVarBase (as of September 15, 2015) and comparison of the current and previous versions are shown in Table 1.

II. Data processing

As shown in Figure 1, data processing in rVarBase includes: variant standardization, regulatory feature analysis, and other analysis.

Data content

Figure 1 Data processing and data content of rVarBase

1. Variant standardization
Official accession and genomic location (with reference to UCSC hg19) of known human variants from dbSNP(version) and dbVar(version) were gotten for subsequent analysis. Novel variants that submitted with their location information were also compared and standardized with information from the two databases.

2. Regulatory feature analysis
1) Chromatin state
8 active states (Active TSS, Flanking Active TSS, Transcr. at gene 5' and 3', Strong transcription, Weak transcription, Genic enhancers, Enhancers, ZNF genes & repeats) and 3 bivalent states (Bivalent/Poised TSS, Flanking Bivalent TSS/Enhancer, Bivalent Enhancer) from the 15-state model that generated by Roadmap final data and ENCODE epigenetic data were utilized to annotate chromatin state of variant¡¯s surrounding region. The detailed chromatin state map was downloaded from the project's supplementary data repository web portal (
2) Variant-related elements obtain and regulation type cataloging.
Genomic location of variant was compared with experimentally validated regulatory elements. Elements that covered or overlapped with input variants are identified as variant-related elements. The regulation types that variants involved are cataloged according to their related elements. As shown in Table 1, six types of regulatory elements (CpG island, TF binding region, chromatin interaction region, lncRNA, mature miRNA and miRNA target sites) are taking account in. The potential binding sites of matched TF families inside TF-binding regions were also identified and compared with variants.
3) Regulated gene analysis
Variant regulated genes are analyzed according to their related elements. For cis-regulatory elements in transcriptional regulation (CpG island, TF binding sites, chromatin interactive regions) their regulated genes are gained according to their genomic proximity to transcript start sites (TSSs) (within the -5000~+500 region surrounding TSS). For RBP-associated RNA sequences, their target genes are mapped by these RNA sequences. For lncRNA and mirRNA, their regulated genes are obtained from experimentally supported databases.

3. Other analysis
1) Extended variants analysis
a. LD-proxies analysis for SNPs. The LD data are compiled from both merged HapMap phases I+II+III genotype data for markers that are up to 200 kb apart and integrated 1000-genomes phase I release data.
b. Gaining extended SNP/ CNVs (from dbSNP or dbVar) that overlapped with variants.
2) Associated phenotype analysis
a. Variant associated disease are obtained from GWAS catalog and the database of CNVD.
b. Variant associated gene expression abundance are required from several eQTL databases and eQTL browser (

III. Reference data

Reference data of regulatory elements and extended analysis were listed in Table 2 and Table 3 separately .

Table2 Reference data of regulatory elements

IV. References

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