Journal
NUCLEIC ACIDS RESEARCH
Volume 41, Issue 5, Pages 2807-2816Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gks1283
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Funding
- National Institutes of Health [NIGMS R01 GM083621]
- Danish Council for Strategic Research [09-061856]
- Burroughs Wellcome Fund [CASI] [1005094]
- Aarhus University Research Foundation [4-56125-437150]
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Recent advances in RNA structure determination include using data from high-throughput probing experiments to improve thermodynamic prediction accuracy. We evaluate the extent and nature of improvements in data-directed predictions for a diverse set of 16S/18S ribosomal sequences using a stochastic model of experimental SHAPE data. The average accuracy for 1000 data-directed predictions always improves over the original minimum free energy (MFE) structure. However, the amount of improvement varies with the sequence, exhibiting a correlation with MFE accuracy. Further analysis of this correlation shows that accurate MFE base pairs are typically preserved in a data-directed prediction, whereas inaccurate ones are not. Thus, the positive predictive value of common base pairs is consistently higher than the directed prediction accuracy. Finally, we confirm sequence dependencies in the directability of thermodynamic predictions and investigate the potential for greater accuracy improvements in the worst performing test sequence.
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