期刊论文详细信息
BMC Bioinformatics
mrSNP: Software to detect SNP effects on microRNA binding
Mehmet Deveci1  Ümit V Çatalyürek2  Amanda Ewart Toland3 
[1] Biomedical Informatics, Computer Science and Engineering, The Ohio State University, Columbus, Ohio, USA
[2] Biomedical Informatics, Electrical and Computer Engineering, The Ohio State University, Columbus, Ohio, USA
[3] Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
关键词: microRNA binding;    mRNA;    SNP;    miRNA;   
Others  :  1087596
DOI  :  10.1186/1471-2105-15-73
 received in 2013-08-27, accepted in 2014-02-26,  发布年份 2014
PDF
【 摘 要 】

Background

MicroRNAs (miRNAs) are short (19-23 nucleotides) non-coding RNAs that bind to sites in the 3’untranslated regions (3’UTR) of a targeted messenger RNA (mRNA). Binding leads to degradation of the transcript or blocked translation resulting in decreased expression of the targeted gene. Single nucleotide polymorphisms (SNPs) have been found in 3’UTRs that disrupt normal miRNA binding or introduce new binding sites and some of these have been associated with disease pathogenesis. This raises the importance of detecting miRNA targets and predicting the possible effects of SNPs on binding sites. In the last decade a number of studies have been conducted to predict the location of miRNA binding sites. However, there have been fewer algorithms published to analyze the effects of SNPs on miRNA binding. Moreover, the existing software has some shortcomings including the requirement for significant manual labor when working with huge lists of SNPs and that algorithms work only for SNPs present in databases such as dbSNP. These limitations become problematic as next-generation sequencing is leading to large numbers of novel variants in 3’UTRs.

Result

In order to overcome these issues, we developed a web-server named mrSNP which predicts the impact of a SNP in a 3’UTR on miRNA binding. The proposed tool reduces the manual labor requirements and allows users to input any SNP that has been identified by any SNP-calling program. In testing the performance of mrSNP on SNPs experimentally validated to affect miRNA binding, mrSNP correctly identified 69% (11/16) of the SNPs disrupting binding.

Conclusions

mrSNP is a highly adaptable and performing tool for predicting the effect a 3’UTR SNP will have on miRNA binding. This tool has advantages over existing algorithms because it can assess the effect of novel SNPs on miRNA binding without requiring significant hands on time.

【 授权许可】

   
2014 Deveci et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150117022321460.pdf 405KB PDF download
Figure 1. 47KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Friedman RC, Farh KK-H, Burge CB, Bartel DP: Most mammalian mrnas are conserved targets of micrornas. Genome Res 2009, 19(1):92-105.
  • [2]Min H, Yoon S: Got target? Computational methods for microRNA target prediction and their extension. Exp Mol Med 2010, 42:233-244.
  • [3]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microrna targets. Cell 2005, 120(1):15-20.
  • [4]Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS: MicroRNA targets in Drosophila. Genome Biol 2003, 5:1.
  • [5]Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R: Fast and effective prediction of microRNA/target duplexes. RNA 2004, 10:1507-1517.
  • [6]Rusinov V, Baev V, Minkov IN, Tabler M: MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence. Nucleic Acids Res 2005, 33:696-700.
  • [7]Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N: Combinatorial microrna target predictions. Nat Genet 2005, 37(5):495-500.
  • [8]Maragkakis M, Reczko M, Simossis VA, Alexiou P, Papadopoulos GL, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Vergoulis T, Koziris N, Sellis T, Tsanakas P, Hatzigeorgiou AG: DIANA-microT web server: elucidating microRNA, functions through target prediction. Nucleic Acids Res 2009, 37:273-276.
  • [9]Maragkakis M, Alexiou P, Papadopoulos GL, Reczko M, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Simossis VA, Sethupathy P, Vergoulis T, Koziris N, Sellis T, Tsanakas P, Hatzigeorgiou AG: Accurate microrna target prediction correlates with protein repression levels. BMC Bioinformatics 2009., 295(1)
  • [10]Sethupathy P, Collins FS: MicroRNA target site polymorphisms and human disease. Trends Genet 2008, 24:489-497.
  • [11]Chen K, Rajewsky N: Natural selection on human microrna binding sites inferred from snp data. Nat Genet 2006, 38(12):1452-1456.
  • [12]Chen K, Song F, Calin GA, Wei Q, Hao X, Zhang W: Polymorphisms in microrna targets: a gold mine for molecular epidemiology. Carcinogenesis 2008, 29(7):1306-1311.
  • [13]Nicoloso MS, Sun H, Spizzo R, Kim H, Wickramasinghe P, Shimizu M, Wojcik SE, Ferdin J, Kunej T, Xiao L, Manoukian S, Secreto G, Ravagnani F, Wang X, Radice P, Croce CM, Davuluri RV, Calin GA: Single-nucleotide polymorphisms inside microrna target sites influence tumor susceptibility. Cancer Res 2010, 70(7):2789-2798.
  • [14]Richardson K, Lai C-Q, Parnell L, Lee Y-C, Ordovas J: A genome-wide survey for snps altering microrna seed sites identifies functional candidates in gwas. BMC Genomics 2011, 12(1):504. BioMed Central Full Text
  • [15]Greliche N, Zeller T, Wild PS, Rotival M, Schillert A, Ziegler A, Deloukas P, Erdmann J, Hengstenberg C, Ouwehand WH, Samani NJ, Schunkert H, Munzel T, Lackner KJ, Cambien F, Goodall AH, Tiret L, Blakenberg S, Tregouet D-A: Comprehensive exploration of the effects of mirna snps on monocyte gene expression. PloS one 2012, 7(9):45863.
  • [16]Barenboim M, Zoltick BJ, Guo Y, Weinberger DR: MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targets. Hum Mutatition 2010, 31(11):1223-1232.
  • [17]Hiard S, Charlier C, Coppieters W, Georges M, Baurain D: Patrocles: a database of polymorphic mirna-mediated gene regulation in vertebrates. Nucleic Acids Res 2010, 38(suppl 1):640-651.
  • [18]Thomas LF, Saito T, Sætrom P: Inferring causative variants in microrna target sites. Nucleic Acids Res 2011, 39(16):109-109.
  • [19]Bruno AE, Li L, Kalabus JL, Pan Y, Yu A, Hu Z: mirdsnp: a database of disease-associated snps and microrna target sites on 3’utrs of human genes. BMC Genomics 2012, 13(1):44. BioMed Central Full Text
  • [20]Liu C, Zhang F, Li T, Lu M, Wang L, Yue W, Zhang D: Mirsnp, a database of polymorphisms altering mirna target sites, identifies mirna-related snps in gwas snps and eqtls. BMC Genomics 2012, 13(1):661. BioMed Central Full Text
  • [21]Ziebarth JD, Bhattacharya A, Chen A, Cui Y: Polymirts database 2.0: linking polymorphisms in microrna target sites with human diseases and complex traits. Nucleic Acids Res 2012, 40(D1):216-221.
  • [22]Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D: The human genome browser at UCSC. Genome Res 2002, 12:996-1006.
  • [23]Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ: mirbase: tools for microrna genomics. Nucleic Acids Res 2008, 36(suppl 1):154-158.
  文献评价指标  
  下载次数:11次 浏览次数:9次