High-order neural networks and kernel methods for peptide-MHC binding prediction

Bioinformatics. 2015 Nov 15;31(22):3600-7. doi: 10.1093/bioinformatics/btv371. Epub 2015 Jul 23.

Abstract

Motivation: Effective computational methods for peptide-protein binding prediction can greatly help clinical peptide vaccine search and design. However, previous computational methods fail to capture key nonlinear high-order dependencies between different amino acid positions. As a result, they often produce low-quality rankings of strong binding peptides. To solve this problem, we propose nonlinear high-order machine learning methods including high-order neural networks (HONNs) with possible deep extensions and high-order kernel support vector machines to predict major histocompatibility complex-peptide binding.

Results: The proposed high-order methods improve quality of binding predictions over other prediction methods. With the proposed methods, a significant gain of up to 25-40% is observed on the benchmark and reference peptide datasets and tasks. In addition, for the first time, our experiments show that pre-training with high-order semi-restricted Boltzmann machines significantly improves the performance of feed-forward HONNs. Moreover, our experiments show that the proposed shallow HONN outperform the popular pre-trained deep neural network on most tasks, which demonstrates the effectiveness of modelling high-order feature interactions for predicting major histocompatibility complex-peptide binding.

Availability and implementation: There is no associated distributable software.

Contact: renqiang@nec-labs.com or mark.gerstein@yale.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Area Under Curve
  • Databases, Protein
  • Epitopes / chemistry
  • Humans
  • Major Histocompatibility Complex*
  • Molecular Sequence Data
  • Neural Networks, Computer*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Binding
  • ROC Curve
  • Support Vector Machine

Substances

  • Epitopes
  • Peptides