A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): Demonstration with IsomiR profiling in colorectal neoplasia

Chung Wah Wu, Jared M. Evans, Shengbing Huang, Douglas W. Mahoney, Brian A. Dukek, William R. Taylor, Tracy C. Yab, Thomas Christopher Smyrk, Jin Jen, John B Kisiel, David A. Ahlquist

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number401
JournalBMC Genomics
Volume19
Issue number1
DOIs
StatePublished - May 25 2018

Keywords

  • Biomarkers
  • Colorectal neoplasms
  • Gene expression profiling
  • High-throughput nucleotide sequencing
  • MicroRNAs

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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    Wu, C. W., Evans, J. M., Huang, S., Mahoney, D. W., Dukek, B. A., Taylor, W. R., Yab, T. C., Smyrk, T. C., Jen, J., Kisiel, J. B., & Ahlquist, D. A. (2018). A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): Demonstration with IsomiR profiling in colorectal neoplasia. BMC Genomics, 19(1), [401]. https://doi.org/10.1186/s12864-018-4794-7