Deep learning for predicting antigen presentation

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Abstract/Contents

Abstract
The presentation of antigens by Human Leukocyte Antigen (HLA) class II molecules is an essential component of adaptive immune responses. Accurate prediction of which antigen fragments are likely to be presented by class II molecules will be of great value for vaccine development and cancer immunotherapies. However, current computational methods trained on in vitro binding data have limitations for accurately predicting class II antigen presentation. Here, we describe MARIA (MHC Analysis with Recurrent Integrated Architecture), a multimodal recurrent neural network for predicting the likelihood of presentation for a given candidate peptide. In addition to in vitro binding measurements, MARIA is trained on peptide HLA ligand sequences identified by mass spectrometry, antigen gene expression levels, and protease cleavage signatures. By integrating these diverse features and leveraging both improved training data and a novel machine learning framework, MARIA (AUC=0.89-0.92) outperformed existing methods in validation data sets and allowed identification of immunogenic epitopes in lymphomas and celiac disease. Across several independent early phase cancer vaccine studies, peptides with high MARIA scores were more likely to elicit strong CD4 T-cell responses. In summary, MARIA improves identification of human peptide immunogens for diverse applications and can be accessed at https://maria.stanford.edu

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Chen, Binbin
Degree supervisor Altman, Russ
Thesis advisor Altman, Russ
Thesis advisor Alizadeh, Ash
Thesis advisor Fire, Andrew Zachary
Thesis advisor Fordyce, Polly
Degree committee member Alizadeh, Ash
Degree committee member Fire, Andrew Zachary
Degree committee member Fordyce, Polly
Associated with Stanford University, Department of Genetics.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Binbin Chen
Note Submitted to the Department of Genetics
Thesis Thesis Ph.D. Stanford University 2020
Location electronic resource

Access conditions

Copyright
© 2020 by Binbin Chen
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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