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Background: MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation.
Results: We introduce a comprehensive approach to sequence-oriented isomiR annotation (CASMIR) to allow unbiased identification of global isomiRs from small RNA sequencing data. In this approach, small RNA reads are maintained as independent sequences instead of being summarized under miRNA names. IsomiR features are identified through step-wise local alignment against canonical forms and precursor sequences. Through customizing the reference database, CASMIR is applicable to isomiR annotation across species. To demonstrate its application, we investigated isomiR profiles in normal and neoplastic human colorectal epithelia. We also ran miRDeep2, a popular miRNA analysis algorithm to validate isomiRs annotated by CASMIR. With CASMIR, specific and biologically relevant isomiR patterns could be identified. We note that specific isomiRs are often more abundant than their canonical forms. We identify isomiRs that are commonly up-regulated in both colorectal cancer and advanced adenoma, and illustrate advantages in targeting isomiRs as potential biomarkers over canonical forms.
Conclusions: Studying miRNAs at the isomiR level could reveal new insight into miRNA biology and inform assay design for specific isomiRs. CASMIR facilitates comprehensive annotation of isomiR features in small RNA sequencing data for isomiR profiling and differential expression analysis.
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http://dx.doi.org/10.1186/s12864-018-4794-7 | DOI Listing |
PLoS Genet
September 2025
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America.
MicroRNAs (miRNAs) are essential regulators of gene expression, yet few comprehensive databases exist for miRNA expression in non-model species, limiting our ability to characterize their roles in gene regulation, development, and disease. Similarly, isomiRs - length and sequence isoforms of canonical miRNAs with potentially altered regulatory targets and functions - have received even less attention in non-model species, including the horse, leaving a critical gap in our understanding of their biological significance. To address these challenges, we developed an open-source, containerized pipeline for identifying and quantifying miRNAs and isomiRs (FARmiR: Framework for Analysis and Refinement of miRNAs), and an associated interactive browser (AIMEE: Animal IsomiR and MiRNA Expression Explorer).
View Article and Find Full Text PDFDatabase (Oxford)
November 2024
Bioinformatics Laboratory, National Institute of Plant Genome Research (NIPGR), Aruna Asaf Ali Marg, New Delhi 110067, India.
Physiol Plant
September 2024
Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Trends Genet
September 2024
Chair for Clinical Bioinformatics, Center for Bioinformatics, Saarland University, 66123 Saarbrücken, Germany; Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarland University Campus, 66123 Saarbrücken, Germany. Electronic address:
MicroRNAs (miRNAs) and isoforms of their archetype, called isomiRs, regulate gene expression via complementary base-pair binding to messenger RNAs (mRNAs). The partially evolutionarily conserved isomiR sequence variations are differentially expressed among tissues, populations, and genders, and between healthy and diseased states. Aiming towards the clinical use of isomiRs as diagnostic biomarkers and for therapeutic purposes, several challenges need to be addressed, including (i) clarification of isomiR definition, (ii) improved annotation in databases with new standardization (such as the mirGFF3 format), and (iii) improved methods of isomiR detection, functional verification, and in silico analysis.
View Article and Find Full Text PDFNoncoding RNA
January 2024
Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia.
The analysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that hold potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids.
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