Format

Send to

Choose Destination
Bioinformatics. 2016 Apr 1;32(7):976-83. doi: 10.1093/bioinformatics/btv520. Epub 2015 Sep 5.

BMix: probabilistic modeling of occurring substitutions in PAR-CLIP data.

Author information

1
Department of Biosystems Science and Engineering and SIB Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.

Abstract

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.

AVAILABILITY AND IMPLEMENTATION:

The model is freely accessible within the BMix toolbox at www.cbg.bsse.ethz.ch/software/BMix, available for Matlab and R.

SUPPLEMENTARY INFORMATION:

Supplementary data is available at Bioinformatics online.

CONTACT:

niko.beerenwinkel@bsse.ethz.ch.

PMID:
26342229
DOI:
10.1093/bioinformatics/btv520
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center