Aberration-corrected ultrafine analysis of miRNA reads at single-base resolution: a k-mer lattice approach
Abstract
Raw sequencing reads of miRNAs contain machine-made substitution errors, or even insertions and deletions (indels). Although the error rate can be low at 0.1%, precise rectification of these errors is critically important because isoform variation analysis at single-base resolution such as novel isomiR discovery, editing events understanding, differential expression analysis, or tissue-specific isoform identification is very sensitive to base positions and copy counts of the reads. Existing error correction methods do not work for miRNA sequencing data attributed to miRNAs’ length and per-read-coverage properties distinct from DNA or mRNA sequencing reads. We present a novel lattice structure combining kmers, (k – 1)mers and (k + 1)mers to address this problem. The method is particularly effective for the correction of indel errors. Extensive tests on datasets having known ground truth of errors demonstrate that the method is able to remove almost all of the errors, without introducing any new error, to improve the data quality from every-50-reads containing one error to every-1300-reads containing one error. Studies on experimental miRNA sequencing datasets show that the errors are often rectified at the 5′ ends and the seed regions of the reads, and that there are remarkable changes after the correction in miRNA isoform abundance, volume of singleton reads, overall entropy, isomiR families, tissue-specific miRNAs, and rare-miRNA quantities.
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All runs were evaluated for adapter sequences, and any samples with barcodes, unique molecular identifiers (UMIs), or adapter sequences on both ends were not processed (n = 1,870 runs were removed).
“All runs were evaluated for adapter sequences, and any samples with barcodes, unique molecular identifiers (UMIs), or adapter sequences on both ends were not processed (n = 1,870 runs were removed) due to the use of miREC in the processing [47].”
From A curated human cellular microRNAome based on 196 primary cell types (2022) · cites this paper as [47]
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Liao, Z., Li, D., Wang, X., Li, L., & Zou, Q. (2018) · Current Bioinformatics · doi:10.2174/1574893611666160609081155 · Cited by 130 · see citing works
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A curated human cellular microRNAome based on 196 primary cell types
Patil, A. H., Baran, A., Brehm, Z. P., McCall, M. N., & Halushka, M. K. (2022) · GigaScience · doi:10.1093/gigascience/giac083 · Cited by 30 · see citing works
- Authors
- Zhang, X., Ping, P., Hutvagner, G., Blumenstein, M., & Li, J.
- Affiliations
- Data Science Institute, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia
- School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia
- Faculty of Engineering and IT, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-07-21
- Volume
- 49
- Issue
- 18
- Pages
- e106-e106
- ISSN
- 0305-1048
- 1362-4962
- PMC
- PMC8631080
- Cited by
- 11
- References
- 2
- Language
- en
- Funders
- Australian Research Council (DP 180100120)
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