Journal
BIOINFORMATICS
Volume 32, Issue 7, Pages 976-983Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btv520
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Funding
- Swiss National Science Foundation [31003A_146579/1]
- Swiss National Science Foundation (SNF) [31003A_146579] Funding Source: Swiss National Science Foundation (SNF)
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Motivation: Photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) is an experimental method based on next-generation sequencing for identifying the RNA interaction sites of a given protein. The method deliberately inserts T-to-C substitutions at the RNA-protein interaction sites, which provides a second layer of evidence compared with other CLIP methods. However, the experiment includes several sources of noise which cause both low-frequency errors and spurious high-frequency alterations. Therefore, rigorous statistical analysis is required in order to separate true T-to-C base changes, following cross-linking, from noise. So far, most of the existing PAR-CLIP data analysis methods focus on discarding the low-frequency errors and rely on high-frequency substitutions to report binding sites, not taking into account the possibility of high-frequency false positive substitutions. Results: Here, we introduce BMix, a new probabilistic method which explicitly accounts for the sources of noise in PAR-CLIP data and distinguishes cross-link induced T-to-C substitutions from low and high-frequency erroneous alterations. We demonstrate the superior speed and accuracy of our method compared with existing approaches on both simulated and real, publicly available human datasets.
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