Structure-based whole-genome realignment reveals many novel noncoding RNAs
Recent genome-wide computational screens that search for conservation of RNA secondary structure in whole-genome alignments (WGAs) have predicted thousands of structural noncoding RNAs (ncRNAs). The sensitivity of such approaches, however, is limited, due to their reliance on sequence-based whole-ge...
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| Muut tekijät: | |
| Aineistotyyppi: | Artikkeli |
| Kieli: | en_US |
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Cold Spring Harbor Laboratory Press
2013
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| Linkit: | http://hdl.handle.net/1721.1/82919 https://orcid.org/0000-0002-2724-7228 |
| _version_ | 1826203609660915712 |
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| author | Will, Sebastian Berger, Bonnie Yu, Michael |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Will, Sebastian Berger, Bonnie Yu, Michael |
| author_sort | Will, Sebastian |
| collection | MIT |
| description | Recent genome-wide computational screens that search for conservation of RNA secondary structure in whole-genome alignments (WGAs) have predicted thousands of structural noncoding RNAs (ncRNAs). The sensitivity of such approaches, however, is limited, due to their reliance on sequence-based whole-genome aligners, which regularly misalign structural ncRNAs. This suggests that many more structural ncRNAs may remain undetected. Structure-based alignment, which could increase the sensitivity, has been prohibitive for genome-wide screens due to its extreme computational costs. Breaking this barrier, we present the pipeline REAPR (RE-Alignment for Prediction of structural ncRNA), which efficiently realigns whole genomes based on RNA sequence and structure, thus allowing us to boost the performance of de novo ncRNA predictors, such as RNAz. Key to the pipeline's efficiency is the development of a novel banding technique for multiple RNA alignment. REAPR significantly outperforms the widely used predictors RNAz and EvoFold in genome-wide screens; in direct comparison to the most recent RNAz screen on D. melanogaster, REAPR predicts twice as many high-confidence ncRNA candidates. Moreover, modENCODE RNA-seq experiments confirm a substantial number of its predictions as transcripts. REAPR's advancement of de novo structural characterization of ncRNAs complements the identification of transcripts from rapidly accumulating RNA-seq data. |
| first_indexed | 2024-09-23T12:40:00Z |
| format | Article |
| id | mit-1721.1/82919 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:40:00Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/829192022-09-28T09:18:19Z Structure-based whole-genome realignment reveals many novel noncoding RNAs Will, Sebastian Berger, Bonnie Yu, Michael Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Mathematics Will, Sebastian Berger, Bonnie Recent genome-wide computational screens that search for conservation of RNA secondary structure in whole-genome alignments (WGAs) have predicted thousands of structural noncoding RNAs (ncRNAs). The sensitivity of such approaches, however, is limited, due to their reliance on sequence-based whole-genome aligners, which regularly misalign structural ncRNAs. This suggests that many more structural ncRNAs may remain undetected. Structure-based alignment, which could increase the sensitivity, has been prohibitive for genome-wide screens due to its extreme computational costs. Breaking this barrier, we present the pipeline REAPR (RE-Alignment for Prediction of structural ncRNA), which efficiently realigns whole genomes based on RNA sequence and structure, thus allowing us to boost the performance of de novo ncRNA predictors, such as RNAz. Key to the pipeline's efficiency is the development of a novel banding technique for multiple RNA alignment. REAPR significantly outperforms the widely used predictors RNAz and EvoFold in genome-wide screens; in direct comparison to the most recent RNAz screen on D. melanogaster, REAPR predicts twice as many high-confidence ncRNA candidates. Moreover, modENCODE RNA-seq experiments confirm a substantial number of its predictions as transcripts. REAPR's advancement of de novo structural characterization of ncRNAs complements the identification of transcripts from rapidly accumulating RNA-seq data. National Institutes of Health (U.S.) (Grant RO1GM081871) 2013-12-13T15:29:41Z 2013-12-13T15:29:41Z 2013-01 2012-05 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/82919 Will, S., M. Yu, and B. Berger. “Structure-based whole-genome realignment reveals many novel noncoding RNAs.” Genome Research 23, no. 6 (June 1, 2013): 1018-1027. © 2013, Published by Cold Spring Harbor Laboratory Press https://orcid.org/0000-0002-2724-7228 en_US http://dx.doi.org/10.1101/gr.137091.111 Genome Research http://creativecommons.org/licenses/by-nc/3.0/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press |
| spellingShingle | Will, Sebastian Berger, Bonnie Yu, Michael Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title | Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title_full | Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title_fullStr | Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title_full_unstemmed | Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title_short | Structure-based whole-genome realignment reveals many novel noncoding RNAs |
| title_sort | structure based whole genome realignment reveals many novel noncoding rnas |
| url | http://hdl.handle.net/1721.1/82919 https://orcid.org/0000-0002-2724-7228 |
| work_keys_str_mv | AT willsebastian structurebasedwholegenomerealignmentrevealsmanynovelnoncodingrnas AT bergerbonnie structurebasedwholegenomerealignmentrevealsmanynovelnoncodingrnas AT yumichael structurebasedwholegenomerealignmentrevealsmanynovelnoncodingrnas |