Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 5;50(W1):W51-W56.
doi: 10.1093/nar/gkac262.

ANANASTRA: annotation and enrichment analysis of allele-specific transcription factor binding at SNPs

Alexandr Boytsov  1   2   3 , Sergey Abramov  1   2   3 , Ariuna Z Aiusheeva  4 , Alexandra M Kasianova  4   5 , Eugene Baulin  2   6 , Ivan A Kuznetsov  7 , Yurii S Aulchenko  8   9 , Semyon Kolmykov  10   11 , Ivan Yevshin  10   11 , Fedor Kolpakov  10   12 , Ilya E Vorontsov  1   4 , Vsevolod J Makeev  1   2   3   13 , Ivan V Kulakovskiy  1   3   4
Affiliations

ANANASTRA: annotation and enrichment analysis of allele-specific transcription factor binding at SNPs

Alexandr Boytsov et al. Nucleic Acids Res. .

Abstract

We present ANANASTRA, https://ananastra.autosome.org, a web server for the identification and annotation of regulatory single-nucleotide polymorphisms (SNPs) with allele-specific binding events. ANANASTRA accepts a list of dbSNP IDs or a VCF file and reports allele-specific binding (ASB) sites of particular transcription factors or in specific cell types, highlighting those with ASBs significantly enriched at SNPs in the query list. ANANASTRA is built on top of a systematic analysis of allelic imbalance in ChIP-Seq experiments and performs the ASB enrichment test against background sets of SNPs found in the same source experiments as ASB sites but not displaying significant allelic imbalance. We illustrate ANANASTRA usage with selected case studies and expect that ANANASTRA will help to conduct the follow-up of GWAS in terms of establishing functional hypotheses and designing experimental verification.

PubMed Disclaimer

Figures

Graphical Abstract
Graphical Abstract
ANANASTRA (https://ananastra.autosome.org) is a web server for annotation and enrichment analysis of allele-specific transcription factor binding at regulatory single-nucleotide polymorphisms (SNPs) in a submitted list of dbSNP IDs or a VCF file.
Figure 1.
Figure 1.
Schematic representation of the ANANASTRA workflow. ANANASTRA accepts a list of dbSNP IDs, generates a unique job Ticket ID, and returns it to the user. The Ticket ID provides the access to the annotation of the SNPs with allele-specific binding events and the enrichment analysis results. The underlying data is taken from ADASTRA which internally utilizes ChIP-Seq data from GTRD and matches allele-specific events against GTEx eQTLs and HOCOMOCO sequence motifs.
Figure 2.
Figure 2.
Highlights of the ANANASTRA case studies. (A) General enrichment of ASBs in the credible set of SNPs associated with inflammatory bowel disease (Example 1 on the website). (B) Motif-concordant ASBs found among the top significant SNPs of COVID19-hg GWAS meta-analyses (Example 2 on the website): rs12482193 (T/C) and rs71327024 (G/T). (C) Motif annotation and ASB effect size illustration of rs12482193 for ELF1 and rs71327024 for MYB of COVID19-hg GWAS meta-analyses (Example 2 on the website). Note, that rs12482193 is shown in the reverse complementary orientation (-strand) to match the motif logo visualization. The bells at the bottom subpanels of each illustration correspond to the alleles preferentially bound by the respective transcription factors in vivo. (D) Accessing the ASB details for rs12482193 and rs71327024 in ADASTRA.
See this image and copyright information in PMC

References

    1. Visscher P.M., Wray N.R., Zhang Q., Sklar P., McCarthy M.I., Brown M.A., Yang J.. 10 Years of GWAS discovery: biology, function, and translation. Am. J. Hum. Genet. 2017; 101:5–22. - PMC - PubMed
    1. Boyle A.P., Hong E.L., Hariharan M., Cheng Y., Schaub M.A., Kasowski M., Karczewski K.J., Park J., Hitz B.C., Weng S.et al. .. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012; 22:1790–1797. - PMC - PubMed
    1. Huang D., Zhou Y., Yi X., Fan X., Wang J., Yao H., Sham P.C., Hao J., Chen K., Li M.J.. VannoPortal: multiscale functional annotation of human genetic variants for interrogating molecular mechanism of traits and diseases. Nucleic. Acids. Res. 2022; 50:D1408–D1416. - PMC - PubMed
    1. Kumar S., Ambrosini G., Bucher P.. SNP2TFBS – a database of regulatory SNPs affecting predicted transcription factor binding site affinity. Nucleic. Acids. Res. 2017; 45:D139–D144. - PMC - PubMed
    1. Vorontsov E.I., Kulakovskiy I.V., Khimulya G., Nikolaeva D.D., Makeev V.J.. PERFECTOS-APE - Predicting Regulatory functional effect of SNPs by approximate P-value estimation. Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms. 2015; Lisbon, Portugal: SCITEPRESS - Science and and Technology Publications; 102–108.

Publication types