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MIRit: an integrative R framework for the identification of impaired miRNA-mRNA regulatory networks in complex
Jacopo Ronchi1,2, Maria Foti1,3
1School of Medicine and Surgery, University of Milano-Bicocca, Monza (MB), 20900, Italy.
Motivation:
MicroRNAs (miRNAs) play a central role in controlling gene expression, and their abnormal activity is frequently linked to disease. Despite advancements in transcriptomic technologies, elucidating miRNA-mediated mechanisms remains challenging due to methodological limitations and a lack of standardized frameworks.
Results:
To overcome these barriers, we developed MIRit, a comprehensive R package designed for the rigorous analysis of miRNA-mRNA interactions. With flexible support for both matched and unmatched datasets, MIRit leverages cutting-edge target identification strategies and applies suitable statistical approaches for each scenario. In this study, we benchmarked the performance of commonly used statistical tests for integrative miRNA analysis and demonstrated the effectiveness of MIRit across three human disease contexts-dilated cardiomyopathy, clear cell renal cell carcinoma, and Alzheimer's disease-by uncovering functionally relevant miRNA-target disruptions consistent with known disease mechanisms. Through its streamlined pipeline and biologically appropriate methods, MIRit enables more reproducible and accurate insights into the complex landscape of post-transcriptional regulation.
Availability And Implementation:
The tool is fully open-source and freely accessible via Bioconductor (https://bioconductor.org/packages/release/bioc/html/MIRit.html), making it readily available to the broader scientific community.
Insights
We developed MIRit, an R package for analyzing microRNA (miRNA)-mRNA interactions in diseases. MIRit provides reproducible insights into gene regulation, aiding disease mechanism discovery.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- MicroRNAs (miRNAs) regulate gene expression; aberrant miRNA activity is linked to various diseases.
- Current transcriptomic technologies face challenges in fully elucidating miRNA-mediated gene regulation mechanisms due to limitations and lack of standardization.
Purpose of the Study:
- To introduce MIRit, a novel R package designed for robust analysis of miRNA-mRNA interactions.
- To provide a standardized framework for investigating miRNA-mediated gene regulation in disease contexts.
Main Methods:
- MIRit supports both matched and unmatched transcriptomic datasets.
- It employs advanced target identification strategies and appropriate statistical methods for different data scenarios.
- The package was benchmarked using common statistical tests for integrative miRNA analysis.
Main Results:
- MIRit demonstrated effectiveness in analyzing miRNA-mRNA interactions across three human diseases: dilated cardiomyopathy, clear cell renal cell carcinoma, and Alzheimer's disease.
- The package successfully identified functionally relevant miRNA-target disruptions consistent with known disease mechanisms.
- MIRit facilitates reproducible and accurate insights into post-transcriptional regulation.
Conclusions:
- MIRit offers a comprehensive and accessible solution for the rigorous analysis of miRNA-mRNA interactions.
- The R package enhances the understanding of miRNA roles in disease pathogenesis.
- MIRit is freely available via Bioconductor, promoting widespread adoption in the scientific community.
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