MiRge - A multiplexed method of processing small RNA-seq data to determine MicroRNA entropy

Alexander Baras, Christopher J. Mitchell, Jason R. Myers, Simone Gupta, Lien Chun Weng, John M. Ashton, Toby C. Cornish, Akhilesh Pandey, Marc K Halushka

Research output: Contribution to journalArticle

Abstract

Small RNA RNA-seq for microRNAs (miRNAs) is a rapidly developing field where opportunities still exist to create better bioinformatics tools to process these large datasets and generate new, useful analyses. We built miRge to be a fast, smart small RNA-seq solution to process samples in a highly multiplexed fashion. miRge employs a Bayesian alignment approach, whereby reads are sequentially aligned against customized mature miRNA, hairpin miRNA, noncoding RNA and mRNA sequence libraries. miRNAs are summarized at the level of raw reads in addition to reads per million (RPM). Reads for all other RNA species (tRNA, rRNA, snoRNA, mRNA) are provided, which is useful for identifying potential contaminants and optimizing small RNA purification strategies. miRge was designed to optimally identify miRNA isomiRs and employs an entropy based statistical measurement to identify differential production of isomiRs. This allowed us to identify decreasing entropy in isomiRs as stem cells mature into retinal pigment epithelial cells. Conversely, we show that pancreatic tumor miRNAs have similar entropy to matched normal pancreatic tissues. In a head-to-head comparison with other miRNA analysis tools (miRExpress 2.0, sRNAbench, omiRAs, miRDeep2, Chimira, UEA small RNA Workbench), miRge was faster (4 to 32-fold) and was among the top-two methods in maximally aligning miRNAs reads per sample. Moreover, miRge has no inherent limits to its multiplexing. miRge was capable of simultaneously analyzing 100 small RNA-Seq samples in 52 minutes, providing an integrated analysis of miRNA expression across all samples. As miRge was designed for analysis of single as well as multiple samples, miRge is an ideal tool for high and low-throughput users. miRge is freely available at http://atlas.pathology.jhu.edu/baras/miRge.html.

Original languageEnglish (US)
Article numbere0143066
JournalPLoS One
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Entropy
entropy
MicroRNAs
microRNA
RNA
Processing
methodology
sampling
Small Nucleolar RNA
Untranslated RNA
Messenger RNA
Retinal Pigments
Bayes Theorem
DNA libraries
Atlases
Pathology
Bioinformatics
Transfer RNA
Computational Biology
Stem cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MiRge - A multiplexed method of processing small RNA-seq data to determine MicroRNA entropy. / Baras, Alexander; Mitchell, Christopher J.; Myers, Jason R.; Gupta, Simone; Weng, Lien Chun; Ashton, John M.; Cornish, Toby C.; Pandey, Akhilesh; Halushka, Marc K.

In: PLoS One, Vol. 10, No. 11, e0143066, 01.11.2015.

Research output: Contribution to journalArticle

Baras, A, Mitchell, CJ, Myers, JR, Gupta, S, Weng, LC, Ashton, JM, Cornish, TC, Pandey, A & Halushka, MK 2015, 'MiRge - A multiplexed method of processing small RNA-seq data to determine MicroRNA entropy', PLoS One, vol. 10, no. 11, e0143066. https://doi.org/10.1371/journal.pone.0143066
Baras, Alexander ; Mitchell, Christopher J. ; Myers, Jason R. ; Gupta, Simone ; Weng, Lien Chun ; Ashton, John M. ; Cornish, Toby C. ; Pandey, Akhilesh ; Halushka, Marc K. / MiRge - A multiplexed method of processing small RNA-seq data to determine MicroRNA entropy. In: PLoS One. 2015 ; Vol. 10, No. 11.
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