Graph-pMHC: graph neural network approach to MHC class II peptide presentation and antibody immunogenicity

Abstract Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been m...

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Veröffentlicht in:Briefings in bioinformatics 2024-03, Vol.25 (3)
Hauptverfasser: Thrift, William John, Perera, Jason, Cohen, Sivan, Lounsbury, Nicolas W, Gurung, Hem R, Rose, Christopher M, Chen, Jieming, Jhunjhunwala, Suchit, Liu, Kai
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container_issue 3
container_start_page
container_title Briefings in bioinformatics
container_volume 25
creator Thrift, William John
Perera, Jason
Cohen, Sivan
Lounsbury, Nicolas W
Gurung, Hem R
Rose, Christopher M
Chen, Jieming
Jhunjhunwala, Suchit
Liu, Kai
description Abstract Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning. Here, we develop graph-pMHC, a graph neural network approach to predict pMHCII presentation. We derive adjacency matrices for pMHCII using Alphafold2-multimer and address the peptide–MHC binding groove alignment problem with a simple graph enumeration strategy. We demonstrate that graph-pMHC dramatically outperforms methods with suboptimal inductive biases, such as the multilayer-perceptron-based NetMHCIIpan-4.0 (+20.17% absolute average precision). Finally, we create an antibody drug immunogenicity dataset from clinical trial data and develop a method for measuring anti-antibody immunogenicity risk using pMHCII presentation models. Our model increases receiver operating characteristic curve (ROC)-area under the ROC curve (AUC) by 2.57% compared to just filtering peptides by hits in OASis alone for predicting antibody drug immunogenicity.
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subjects Adaptive immunity
Antibodies
Antigen Presentation
Antigens
Datasets
Defence mechanisms
Drugs
Enumeration
Graph neural networks
Grooves
Histocompatibility Antigens Class II - chemistry
Humans
Immune response
Immune system
Immunity
Immunogenicity
Immunosuppressive agents
Machine learning
Major histocompatibility complex
Mass spectrometry
Mass spectroscopy
Measurement methods
Multilayers
Neural networks
Neural Networks, Computer
Pathogens
Peptides
Peptides - chemistry
Problem Solving Protocol
title Graph-pMHC: graph neural network approach to MHC class II peptide presentation and antibody immunogenicity
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