2. Academic Validation
  3. MDEHT: a multivariate approach for detecting differential expression of microRNA isoform data in RNA-sequencing studies

MDEHT: a multivariate approach for detecting differential expression of microRNA isoform data in RNA-sequencing studies

  • Bioinformatics. 2020 May 1;36(9):2657-2664. doi: 10.1093/bioinformatics/btaa015.
Md Amanullah 1,  Mengqian Yu 2,  Xiwei Sun 2 3,  Aoran Luo 1,  Qing Zhou 1,  Liyuan Zhou 2,  Ling Hou 1,  Wei Wang 3 4,  Weiguo Lu 1,  Pengyuan Liu 2 4 5,  Yan Lu 1
Affiliations

Affiliations

  • 1 Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province and Department of Gynecologic Oncology, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
  • 2 Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
  • 3 Institute for Advanced Research, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 4 Department of Pathology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
  • 5 Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
PMID: 31930386 DOI: 10.1093/bioinformatics/btaa015
Abstract

Motivation: miRNA isoforms (isomiRs) are produced from the same arm as the archetype miRNA with a few nucleotides different at 5 and/or 3 termini. These well-conserved isomiRs are functionally important and have contributed to the evolution of miRNA genes. Accurate detection of differential expression of miRNAs can bring new insights into the cellular function of miRNA and a further improvement in miRNA-based diagnostic and prognostic applications. However, very few methods take isomiR variations into account in the analysis of miRNA differential expression.

Results: To overcome this challenge, we developed a novel approach to take advantage of the multidimensional structure of isomiR data from the same miRNAs, termed as a multivariate differential expression by Hotelling's T2 test (MDEHT). The utilization of the information hidden in isomiRs enables MDEHT to increase the power of identifying differentially expressed miRNAs that are not marginally detectable in univariate testing methods. We conducted rigorous and unbiased comparisons of MDEHT with seven commonly used tools in simulated and real datasets from The Cancer Genome Atlas. Our comprehensive evaluations demonstrated that the MDEHT method was robust among various datasets and outperformed Other commonly used tools in terms of Type I error rate, true positive rate and reproducibility.

Availability and implementation: The source code for identifying and quantifying isomiRs and performing miRNA differential expression analysis is available at https://github.com/amanzju/MDEHT.

Supplementary information: Supplementary data are available at Bioinformatics online.

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