A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4794-7 |
| _version_ | 1818033471356928000 |
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| author | Chung Wah Wu Jared M. Evans Shengbing Huang Douglas W. Mahoney Brian A. Dukek William R. Taylor Tracy C. Yab Thomas C. Smyrk Jin Jen John B. Kisiel David A. Ahlquist |
| author_facet | Chung Wah Wu Jared M. Evans Shengbing Huang Douglas W. Mahoney Brian A. Dukek William R. Taylor Tracy C. Yab Thomas C. Smyrk Jin Jen John B. Kisiel David A. Ahlquist |
| author_sort | Chung Wah Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T06:23:47Z |
| format | Article |
| id | doaj.art-f0b7bd83d6ca4a98b4c2c70326af6767 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-10T06:23:47Z |
| publishDate | 2018-05-01 |
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| series | BMC Genomics |
| spelling | doaj.art-f0b7bd83d6ca4a98b4c2c70326af67672022-12-22T01:59:17ZengBMCBMC Genomics1471-21642018-05-0119111210.1186/s12864-018-4794-7A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasiaChung Wah Wu0Jared M. Evans1Shengbing Huang2Douglas W. Mahoney3Brian A. Dukek4William R. Taylor5Tracy C. Yab6Thomas C. Smyrk7Jin Jen8John B. Kisiel9David A. Ahlquist10Division of Gastroenterology and Hepatology, Mayo ClinicDivision of Biomedical Statistics and Informatics, Mayo ClinicDivision of Bioinformatics and Computational Biology, University of Minnesota RochesterDivision of Biomedical Statistics and Informatics, Mayo ClinicDivision of Gastroenterology and Hepatology, Mayo ClinicDivision of Gastroenterology and Hepatology, Mayo ClinicDivision of Gastroenterology and Hepatology, Mayo ClinicDivision of Anatomic Pathology, Mayo ClinicGenome Analysis Core, Medical Genome Facility, Mayo ClinicDivision of Gastroenterology and Hepatology, Mayo ClinicDivision of Gastroenterology and Hepatology, Mayo ClinicAbstract 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.http://link.springer.com/article/10.1186/s12864-018-4794-7MicroRNAsHigh-throughput nucleotide sequencingColorectal neoplasmsGene expression profilingBiomarkers |
| spellingShingle | Chung Wah Wu Jared M. Evans Shengbing Huang Douglas W. Mahoney Brian A. Dukek William R. Taylor Tracy C. Yab Thomas C. Smyrk Jin Jen John B. Kisiel David A. Ahlquist A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia BMC Genomics MicroRNAs High-throughput nucleotide sequencing Colorectal neoplasms Gene expression profiling Biomarkers |
| title | A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia |
| title_full | A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia |
| title_fullStr | A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia |
| title_full_unstemmed | A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia |
| title_short | A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia |
| title_sort | comprehensive approach to sequence oriented isomir annotation casmir demonstration with isomir profiling in colorectal neoplasia |
| topic | MicroRNAs High-throughput nucleotide sequencing Colorectal neoplasms Gene expression profiling Biomarkers |
| url | http://link.springer.com/article/10.1186/s12864-018-4794-7 |
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