Dysregulation of miRNA isoform level at 5ʹ end in Alzheimer's disease

• An entropy-based model is bulit to detect the miRNA isoform level at the 5′ end.
• Many miRNAs are found with significant changes of isoform levels in AD.
• isomiRs of AD related miRNAs may contribute to the nervous system.
• MIH5 are more stable than previous method for AD related miRNA detecting.

Alzheimer's disease (AD) is the most common form of dementia, whose mechanism is still not yet fully understood. A miRNA-based signature method, commonly according to the changes of expression levels, is widely used for AD analysis in previous studies. Recently, miRNA isoforms called as isomiR variants, which is considered to play important biological roles, have been demonstrated as the applications of high throughput sequencing platforms. Here, we presented an entropy-based model to detect the miRNA isoform level at the 5′ end, and found many miRNAs with significant changes of isoform levels between the early stage and the late stage of AD by the application of this model to the public data. The statistical significance of the overlap between isoform-level changed miRNAs and AD related miRNAs extracted from HMDD2 supports that these miRNA isoforms are not degradation products. Based on the most common isomiR seed analysis of isoform-level changed AD related miRNAs, the predicted targets are also found to be enriched for genes involved in transcriptional regulation and the nervous system. After comparing with the expression level based method, we detected that changes of 5′ isoform levels are more stable than those of expression levels for AD related miRNA detecting.