De novo detection of differentially bound regions for ChIP-seq data using peaks and windows: controlling error rates correctly
- Details
- Publication Year 2014-05-22,Volume 42,Issue #11,Page e95
- Journal Title
- Nucleic Acids Research
- Publication Type
- Journal Article
- Abstract
- A common aim in ChIP-seq experiments is to identify changes in protein binding patterns between conditions, i.e. differential binding. A number of peak- and window-based strategies have been developed to detect differential binding when the regions of interest are not known in advance. However, careful consideration of error control is needed when applying these methods. Peak-based approaches use the same data set to define peaks and to detect differential binding. Done improperly, this can result in loss of type I error control. For window-based methods, controlling the false discovery rate over all detected windows does not guarantee control across all detected regions. Misinterpreting the former as the latter can result in unexpected liberalness. Here, several solutions are presented to maintain error control for these de novo counting strategies. For peak-based methods, peak calling should be performed on pooled libraries prior to the statistical analysis. For window-based methods, a hybrid approach using Simes' method is proposed to maintain control of the false discovery rate across regions. More generally, the relative advantages of peak- and window-based strategies are explored using a range of simulated and real data sets. Implementations of both strategies also compare favourably to existing programs for differential binding analyses.
- Publisher
- OUP
- Research Division(s)
- Bioinformatics
- Publisher's Version
- https://doi.org/10.1093/nar/gku351
- Open Access at Publisher's Site
http://nar.oxfordjournals.org/content/early/2014/05/22/nar.gku351.long- Terms of Use/Rights Notice
- © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Creation Date: 2014-05-26 08:08:16