Genome-wide identification of clusters of predicted microRNA binding sites as microRNA sponge candidates

PloS One
Xiaoyong PanJan Gorodkin

Abstract

The number of discovered natural miRNA sponges in plants, viruses, and mammals is increasing steadily. Some sponges like ciRS-7 for miR-7 contain multiple nearby miRNA binding sites. We hypothesize that such clusters of miRNA binding sites on the genome can function together as a sponge. No systematic effort has been made in search for clusters of miRNA targets. Here, we, to our knowledge, make the first genome-wide target site predictions for clusters of mature human miRNAs. For each miRNA, we predict the target sites on a genome-wide scale, build a graph with edge weights based on the pairwise distances between sites, and apply Markov clustering to identify genomic regions with high binding site density. Significant clusters are then extracted based on cluster size difference between real and shuffled genomes preserving local properties such as the GC content. We then use conservation and binding energy to filter a final set of miRNA target site clusters or sponge candidates. Our pipeline predicts 3673 sponge candidates for 1250 miRNAs, including the experimentally verified miR-7 sponge ciRS-7. In addition, we point explicitly to 19 high-confidence candidates overlapping annotated genomic sequence. The full list of candidates...Continue Reading

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Citations

Jan 24, 2020·Journal of Animal Science and Biotechnology·Emilio Mármol-SánchezMarcel Amills
Feb 28, 2020·Briefings in Bioinformatics·Liang ChenGarry Wong
Apr 9, 2020·Frontiers in Bioengineering and Biotechnology·Feili LiuTao Huang
Oct 12, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Dandan LiJinming Li
Jan 13, 2021·Scientific Reports·Endika Varela-MartínezBegoña M Jugo

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Methods Mentioned

BETA
antisense oligonucleotide
CLIP-Seq
interaction prediction

Software Mentioned

phyloP
UCSC browser
MCL
Tandem Repeats Finder
RIsearch
BLAST
TargetScan
GUUGle
RNAplfold
RepeatMasker

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