Novel microRNA discovery using small RNA sequencing in post-mortem human brain

BMC Genomics

Research Article

Alexandra Dumitriu¹  Joli Bregu¹  Christian Wake²  Adam Labadorf²  Richard H. Myers³  Anita L. DeStefano⁴  Andrew G. Hoss⁵  Kenneth H. Albrecht⁶ 

[1] Department of Neurology, Boston University School of Medicine, Boston, USA;Department of Neurology, Boston University School of Medicine, Boston, USA;Bioinformatics Program, Boston University, Boston, USA;Department of Neurology, Boston University School of Medicine, Boston, USA;Bioinformatics Program, Boston University, Boston, USA;Graduate Program in Genetics and Genomics, Boston University School of Medicine, Boston, USA;Genome Science Institute, Boston University School of Medicine, Boston, USA;Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, USA;Department of Biostatistics, Boston University School of Public Health, Boston, USA;Department of Neurology, Boston University School of Medicine, Boston, USA;Genome Science Institute, Boston University School of Medicine, Boston, USA;Department of Biostatistics, Boston University School of Public Health, Boston, USA;Department of Neurology, Boston University School of Medicine, Boston, USA;Graduate Program in Genetics and Genomics, Boston University School of Medicine, Boston, USA;Genome Science Institute, Boston University School of Medicine, Boston, USA;Section of Biomedical Genetics, Department of Medicine, Boston University School of Medicine, Boston, USA;

关键词: MicroRNA;    miRNA sequencing;    Novel miRNA discovery;    Prefrontal cortex;    Neurodegenerative disease;   

DOI  :  10.1186/s12864-016-3114-3

 received in 2016-02-03, accepted in 2016-09-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression mainly through translational repression of target mRNA molecules. More than 2700 human miRNAs have been identified and some are known to be associated with disease phenotypes and to display tissue-specific patterns of expression.MethodsWe used high-throughput small RNA sequencing to discover novel miRNAs in 93 human post-mortem prefrontal cortex samples from individuals with Huntington’s disease (n = 28) or Parkinson’s disease (n = 29) and controls without neurological impairment (n = 36). A custom miRNA identification analysis pipeline was built, which utilizes miRDeep* miRNA identification and result filtering based on false positive rate estimates.ResultsNinety-nine novel miRNA candidates with a false positive rate of less than 5 % were identified. Thirty-four of the candidate miRNAs show sequence similarity with known mature miRNA sequences and may be novel members of known miRNA families, while the remaining 65 may constitute previously undiscovered families of miRNAs. Nineteen of the 99 candidate miRNAs were replicated using independent, publicly-available human brain RNA-sequencing samples, and seven were experimentally validated using qPCR.ConclusionsWe have used small RNA sequencing to identify 99 putative novel miRNAs that are present in human brain samples.

【 授权许可】

CC BY   
© The Author(s). 2016