Title
Modeling positional effects of regulatory sequences with spline transformations increases prediction accuracy of deep neural networks.
Abstract
Motivation: Regulatory sequences are not solely defined by their nucleic acid sequence but also by their relative distances to genomic landmarks such as transcription start site, exon boundaries or polyadenylation site. Deep learning has become the approach of choice for modeling regulatory sequences because of its strength to learn complex sequence features. However, modeling relative distances to genomic landmarks in deep neural networks has not been addressed. Results: Here we developed spline transformation, a neural network module based on splines to flexibly and robustly model distances. Modeling distances to various genomic landmarks with spline transformations significantly increased state-of-the-art prediction accuracy of in vivo RNAb-inding protein binding sites for 120 out of 123 proteins. We also developed a deep neural network for human splice branchpoint based on spline transformations that outperformed the current best, already distance-based, machine learning model. Compared to piecewise linear transformation, as obtained by composition of rectified linear units, spline transformation yields higher prediction accuracy as well as faster and more robust training. As spline transformation can be applied to further quantities beyond distances, such as methylation or conservation, we foresee it as a versatile component in the genomics deep learning toolbox.
Year
DOI
Venue
2018
10.1093/bioinformatics/btx727
BIOINFORMATICS
Keywords
Field
DocType
spline transformation,deep learning,cis-regulatory element,RNA-binding protein,splicing
Spline (mathematics),Rectifier (neural networks),Biology,Genomics,Artificial intelligence,Deep learning,Bioinformatics,Artificial neural network,Deep neural networks,Python (programming language),Regulatory sequence
Journal
Volume
Issue
ISSN
34
8
1367-4803
Citations 
PageRank 
References 
2
0.37
3
Authors
4
Name
Order
Citations
PageRank
Žiga Avsec120.71
mohammadamin barekatain2564.92
Jun Cheng38527.49
Julien Gagneur431.67