DeepSeqPan, a novel deep convolutional neural network model for pan-specific class I HLA-peptide binding affinity prediction

Interactions between human leukocyte antigens (HLAs) and peptides play a critical role in the human immune system. Accurate computational prediction of HLA-binding peptides can be used for peptide drug discovery. Currently, the best prediction algorithms are neural network based pan-specific models, which take advantage of the large amount of data across HLA alleles. However, current pan-specific models are all based on the pseudo sequence encoding for modeling the binding context and depend on the available HLA protein-peptide bound structures. In this work, we proposed a novel deep convolutional neural network model (DCNN) for HLA-peptide binding prediction, in which the encoding of the HLA sequence and the binding context are both learned by the network itself without requiring the HLA-peptide bound structure information. Our DCNN model is also characterized by its binding context extraction layer and dual outputs with both binding affinity output and binding probability outputs. Evaluation on public benchmark datasets shows that our DeepSeqPan model without HLA structural information in training achieves state-of-the-art performance on a large number of HLA alleles with good generalization capability. Since our model only needs raw sequences from the HLA-peptide binding pairs, it can be applied to binding predictions of HLAs without structure information and can also be applied to other protein binding problems such as protein-DNA and protein-RNA bindings. The implementation code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPan.

[1]  B. Frey,et al.  Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning , 2015, Nature Biotechnology.

[2]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[3]  Deborah Hix,et al.  The immune epitope database (IEDB) 3.0 , 2014, Nucleic Acids Res..

[4]  Jian Wang,et al.  PSSMHCpan: a novel PSSM-based software for predicting class I peptide-HLA binding affinity , 2017, GigaScience.

[5]  Dongsup Kim,et al.  Deep convolutional neural networks for pan-specific peptide-MHC class I binding prediction , 2017, BMC Bioinformatics.

[6]  Morten Nielsen,et al.  Quantitative Predictions of Peptide Binding to Any HLA-DR Molecule of Known Sequence: NetMHCIIpan , 2008, PLoS Comput. Biol..

[7]  Morten Nielsen,et al.  NetMHCcons: a consensus method for the major histocompatibility complex class I predictions , 2011, Immunogenetics.

[8]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[9]  Alessandro Sette,et al.  Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method , 2005, BMC Bioinformatics.

[10]  Sneh Lata,et al.  MHCBN 4.0: A database of MHC/TAP binding peptides and T-cell epitopes , 2009, BMC Research Notes.

[11]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[12]  Alex Rubinsteyn,et al.  MHCflurry: Open-Source Class I MHC Binding Affinity Prediction. , 2018, Cell systems.

[13]  Jean-Philippe Vert,et al.  Efficient peptide-MHC-I binding prediction for alleles with few known binders , 2008, Bioinform..

[14]  Yeeleng Scott Vang,et al.  HLA class I binding prediction via convolutional neural networks , 2017 .

[15]  Morten Nielsen,et al.  Automated benchmarking of peptide-MHC class I binding predictions , 2015, Bioinform..

[16]  O. Lund,et al.  NetMHCpan, a method for MHC class I binding prediction beyond humans , 2008, Immunogenetics.

[17]  Morten Nielsen,et al.  NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8–11 , 2008, Nucleic Acids Res..

[18]  Xiaohui Xie,et al.  HLA class I binding prediction via convolutional neural networks , 2017, bioRxiv.

[19]  Hao Ye,et al.  sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides , 2016, Scientific Reports.

[20]  Morten Nielsen,et al.  The PickPocket method for predicting binding specificities for receptors based on receptor pocket similarities: application to MHC-peptide binding , 2009, Bioinform..

[21]  M. Nielsen,et al.  NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets , 2016, Genome Medicine.

[22]  Ming Yang,et al.  DeepFace: Closing the Gap to Human-Level Performance in Face Verification , 2014, 2014 IEEE Conference on Computer Vision and Pattern Recognition.

[23]  Hiroshi Mamitsuka,et al.  Toward more accurate pan-specific MHC-peptide binding prediction: a review of current methods and tools , 2011, Briefings Bioinform..

[24]  O. Stegle,et al.  DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning , 2016, Genome Biology.

[25]  Jianjun Hu,et al.  DeepMHC: Deep Convolutional Neural Networks for High-performance peptide-MHC Binding Affinity Prediction , 2017, bioRxiv.

[26]  James Robinson,et al.  The IPD and IMGT/HLA database: allele variant databases , 2014, Nucleic Acids Res..