Abstract
MicroRNA (miRNA) locus has been found that can generate a series of varied isomiR sequences. Most studies always focus on determining miRNA level, however, the canonical miRNA sequence is only a specific member in the multiple isomiRs. Some studies have shown that isomiR sequences play versatile roles in biological progress, and the analysis and research should be simultaneously performed at the miRNA/isomiR levels. Based on the biological characteristics of miRNA and isomiR, we developed miR-isomiRExp to analyze expression pattern of miRNA at the miRNA/isomiR levels, provide insights into tracking miRNA/isomiR maturation and processing mechanisms, and reveal functional characteristics of miRNA/isomiR. Simultaneously, we also performed expression analysis of specific human diseases using public small RNA sequencing datasets based on the analysis platform, which may help in surveying the potential deregulated miRNA/isomiR expression profiles, especially sequence and function-related isomiRs for further interaction analysis and study. The miR-isomiRExp platform provides miRNA/isomiR expression patterns and more information to study deregulated miRNA loci and detailed isomiR sequences. This comprehensive analysis will enrich experimental miRNA studies. miR-isomiRExp is available at http://server.malab.cn/miRisomiRExp/.
Highlights
MicroRNA has been extensively studied due to its flexible and crucial regulatory role, many literatures have validated that miRNA is not a single sequence, and each miRNA locus can generate a series of isomiRs with various sequences and expression patterns[1,2]
The sequence diversity of multiple isomiRs is similar to miRNA sequence diversity across different animal species, suggesting that the phenomenon of multiple isomiRs may facilitate in identifying the optimal sequence involved in functional and evolutionary history[15]
The multiple isomiRs are rarely examined and in-depthly studied and most studies only focus on the canonical miRNA sequence
Summary
IsomiR include the following steps (Fig. 1): (1) the candidate miRNA/isomiR expression profiles are obtained through mapping the genome and known precursor miRNA (pre-miRNA) sequences from the miRBase database (version 21.0, http://www.mirbase.org/)[26] using the Bowtie software[27]. Loci on the chromosomes; (6) the phenomenon of arm-switching is simultaneously analyzed at the isomiR levels because many miRNA genes have been determined to generate two mature miRNA products, thereby can be used to track and predict dynamic miRNA and isomiR expression profiles. A special miRNA class is defined according to classification and clustering the “seed sequences”, and further analysis is performed based on sequence and expression levels. According to the analysis pipeline, we further performed miRNA/isomiR analysis using small RNA sequencing datasets from public database of The Cancer Genome Atlas (TCGA) pilot project, including breast cancer, colon and rectal adenocarcinoma, head and neck squamous cell carcinoma, and other human diseases. The web server is written in Python, and source_codes can be downloaded from the web server (http://server.malab.cn/miRisomiRExp/)
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