Computational modeling of in vivo and in vitro protein-DNA interactions by multiple instance learning.
BACKGROUND
The study of transcriptional regulation is still difficult yet fundamental in molecular biology research. While the development of both in vivo and in vitro profiling techniques have significantly enhanced our knowledge of transcription factor (TF)-DNA interactions, computational models of TF-DNA interactions are relatively simple and may not reveal sufficient biological insight. In particular, supervised learning based models for TF-DNA interactions attempt to map sequence-level features ( k -mers) to binding event but usually ignore the location of k -mers, which can cause data fragmentation and consequently inferior model performance.


RESULTS
Here, we propose a novel algorithm based on the so-called multiple-instance learning (MIL) paradigm. MIL breaks each DNA sequence into multiple overlapping subsequences and models each subsequence separately, therefore implicitly takes into consideration binding site locations, resulting in both higher accuracy and better interpretability of the models. The result from both in vivo and in vitro TF-DNA interaction data show that our approach significantly outperform conventional single-instance learning based algorithms. Importantly, the models learned from in vitro data using our approach can predict in vivo binding with very good accuracy. In addition, the location information obtained by our method provides additional insight for motif finding results from ChIP-Seq data. Finally, our approach can be easily combined with other state-of-the-art TF-DNA interaction modeling methods.


METHODS
http://www.cs.utsa.edu/∼jruan/MIL/.


BACKGROUND
jianhua.ruan@utsa.edu.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA.
Zhen
Z
Gao
Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA.
Jianhua
J
Ruan
D001665:Binding Sites; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D000069553:Supervised Machine Learning; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D014157:Transcription Factors; D004247:DNA