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miRspring: a compact standalone research tool for analyzing miRNA-seq data.

Humphreys DT, Suter CM - Nucleic Acids Res. (2013)

Bottom Line: Additionally, we report on a new class of miRNA variants, which we term seed-isomiRs, identified through the novel visualization tools of the miRspring document.Further investigation identified that ∼30% of human miRBase entries are likely to have a seed-isomiR.We believe that miRspring will be a highly useful research tool that will enhance the analysis of miRNA data sets and thus increase our understanding of miRNA biology.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, 2010, Australia and St Vincent's Clinical School, University of New South Wales, 2052, Australia.

ABSTRACT
High-throughput sequencing for microRNA (miRNA) profiling has revealed a vast complexity of miRNA processing variants, but these are difficult to discern for those without bioinformatics expertise and large computing capability. In this article, we present miRNA Sequence Profiling (miRspring) (http://mirspring.victorchang.edu.au), a software solution that creates a small portable research document that visualizes, calculates and reports on the complexities of miRNA processing. We designed an index-compression algorithm that allows the miRspring document to reproduce a complete miRNA sequence data set while retaining a small file size (typically <3 MB). Through analysis of 73 public data sets, we demonstrate miRspring's features in assessing quality parameters, miRNA cluster expression levels and miRNA processing. Additionally, we report on a new class of miRNA variants, which we term seed-isomiRs, identified through the novel visualization tools of the miRspring document. Further investigation identified that ∼30% of human miRBase entries are likely to have a seed-isomiR. We believe that miRspring will be a highly useful research tool that will enhance the analysis of miRNA data sets and thus increase our understanding of miRNA biology.

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Analysis of published data sets using the miRspring document. (A) Differential expression or processing of miRNA precursors within a miRNA cluster across different human tissues. (B) Proportion of non-miRBase defined seeds identified in human tissues. Majority are derived from isomiRs of defined-processed miRNAs, and the remainder is derived from miRNAs that are processed from miRBase precursor arms that in miRBase v19 have no defined mature sequence (unannotated) or other processed sequences. (C) Vennn diagram showing the number of miRNAs and their isomiRs that have identical seeds. Seed-isomiRs are highlighted in gray. (D) Examples of interesting seed-isomiRs. The +1 isomiR of miR-27b has the same seed as miR-128 and miR-3681. Similarly, the +1 isomiR derived from the let-7 family has the same seed as miR-196 family. (E) The proportion of miRNAs and their isomiRs that have the canonical miR-196 seed (AGGUAGU) in different human tissues.
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gkt485-F3: Analysis of published data sets using the miRspring document. (A) Differential expression or processing of miRNA precursors within a miRNA cluster across different human tissues. (B) Proportion of non-miRBase defined seeds identified in human tissues. Majority are derived from isomiRs of defined-processed miRNAs, and the remainder is derived from miRNAs that are processed from miRBase precursor arms that in miRBase v19 have no defined mature sequence (unannotated) or other processed sequences. (C) Vennn diagram showing the number of miRNAs and their isomiRs that have identical seeds. Seed-isomiRs are highlighted in gray. (D) Examples of interesting seed-isomiRs. The +1 isomiR of miR-27b has the same seed as miR-128 and miR-3681. Similarly, the +1 isomiR derived from the let-7 family has the same seed as miR-196 family. (E) The proportion of miRNAs and their isomiRs that have the canonical miR-196 seed (AGGUAGU) in different human tissues.

Mentions: Suggested genomic distances that define a miRNA cluster range from 6 to 50 Kb (23,24), and owing to the lack of a strict definition, miRspring offers the user a number of distances that can be used to define the boundaries of a genomically clustered miRNAs. Using the output generated from the miRspring ‘miRNA cluster counts’ and custom scripts, we identified that the expression pattern within many miRNA clusters was conserved across tissues, and that this was independent of transcription direction (Supplementary Table S3). For one potential pri-miR polycistronic cluster, we identified a ranked expression difference of a individual miRNA in different tissues (Figure 3A). With the exception of lung and ovary, miR-365b was the predominant miRNA expressed from this cluster and suggests that this precursors of this cluster may be differentially processed.Figure 3.


miRspring: a compact standalone research tool for analyzing miRNA-seq data.

Humphreys DT, Suter CM - Nucleic Acids Res. (2013)

Analysis of published data sets using the miRspring document. (A) Differential expression or processing of miRNA precursors within a miRNA cluster across different human tissues. (B) Proportion of non-miRBase defined seeds identified in human tissues. Majority are derived from isomiRs of defined-processed miRNAs, and the remainder is derived from miRNAs that are processed from miRBase precursor arms that in miRBase v19 have no defined mature sequence (unannotated) or other processed sequences. (C) Vennn diagram showing the number of miRNAs and their isomiRs that have identical seeds. Seed-isomiRs are highlighted in gray. (D) Examples of interesting seed-isomiRs. The +1 isomiR of miR-27b has the same seed as miR-128 and miR-3681. Similarly, the +1 isomiR derived from the let-7 family has the same seed as miR-196 family. (E) The proportion of miRNAs and their isomiRs that have the canonical miR-196 seed (AGGUAGU) in different human tissues.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3753622&req=5

gkt485-F3: Analysis of published data sets using the miRspring document. (A) Differential expression or processing of miRNA precursors within a miRNA cluster across different human tissues. (B) Proportion of non-miRBase defined seeds identified in human tissues. Majority are derived from isomiRs of defined-processed miRNAs, and the remainder is derived from miRNAs that are processed from miRBase precursor arms that in miRBase v19 have no defined mature sequence (unannotated) or other processed sequences. (C) Vennn diagram showing the number of miRNAs and their isomiRs that have identical seeds. Seed-isomiRs are highlighted in gray. (D) Examples of interesting seed-isomiRs. The +1 isomiR of miR-27b has the same seed as miR-128 and miR-3681. Similarly, the +1 isomiR derived from the let-7 family has the same seed as miR-196 family. (E) The proportion of miRNAs and their isomiRs that have the canonical miR-196 seed (AGGUAGU) in different human tissues.
Mentions: Suggested genomic distances that define a miRNA cluster range from 6 to 50 Kb (23,24), and owing to the lack of a strict definition, miRspring offers the user a number of distances that can be used to define the boundaries of a genomically clustered miRNAs. Using the output generated from the miRspring ‘miRNA cluster counts’ and custom scripts, we identified that the expression pattern within many miRNA clusters was conserved across tissues, and that this was independent of transcription direction (Supplementary Table S3). For one potential pri-miR polycistronic cluster, we identified a ranked expression difference of a individual miRNA in different tissues (Figure 3A). With the exception of lung and ovary, miR-365b was the predominant miRNA expressed from this cluster and suggests that this precursors of this cluster may be differentially processed.Figure 3.

Bottom Line: Additionally, we report on a new class of miRNA variants, which we term seed-isomiRs, identified through the novel visualization tools of the miRspring document.Further investigation identified that ∼30% of human miRBase entries are likely to have a seed-isomiR.We believe that miRspring will be a highly useful research tool that will enhance the analysis of miRNA data sets and thus increase our understanding of miRNA biology.

View Article: PubMed Central - PubMed

Affiliation: Molecular Genetics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, 2010, Australia and St Vincent's Clinical School, University of New South Wales, 2052, Australia.

ABSTRACT
High-throughput sequencing for microRNA (miRNA) profiling has revealed a vast complexity of miRNA processing variants, but these are difficult to discern for those without bioinformatics expertise and large computing capability. In this article, we present miRNA Sequence Profiling (miRspring) (http://mirspring.victorchang.edu.au), a software solution that creates a small portable research document that visualizes, calculates and reports on the complexities of miRNA processing. We designed an index-compression algorithm that allows the miRspring document to reproduce a complete miRNA sequence data set while retaining a small file size (typically <3 MB). Through analysis of 73 public data sets, we demonstrate miRspring's features in assessing quality parameters, miRNA cluster expression levels and miRNA processing. Additionally, we report on a new class of miRNA variants, which we term seed-isomiRs, identified through the novel visualization tools of the miRspring document. Further investigation identified that ∼30% of human miRBase entries are likely to have a seed-isomiR. We believe that miRspring will be a highly useful research tool that will enhance the analysis of miRNA data sets and thus increase our understanding of miRNA biology.

Show MeSH
Related in: MedlinePlus