TY - JOUR
T1 - GraphMHC
T2 - Neoantigen prediction model applying the graph neural network to molecular structure
AU - Jeong, Hoyeon
AU - Cho, Young Rae
AU - Gim, Jungsoo
AU - Cha, Seung Kuy
AU - Kim, Maengsup
AU - Kang, Dae Ryong
N1 - Publisher Copyright:
© 2024 Public Library of Science. All rights reserved.
PY - 2024/3
Y1 - 2024/3
N2 - Neoantigens are tumor-derived peptides and are biomarkers that can predict prognosis related to immune checkpoint inhibition by estimating their binding to major histocompatibility complex (MHC) proteins. Although deep neural networks have been primarily used for these prediction models, it is difficult to interpret the models reported thus far as accurately representing the interactions between biomolecules. In this study, we propose the GraphMHC model, which utilizes a graph neural network model applied to molecular structure to simulate the binding between MHC proteins and peptide sequences. Amino acid sequences sourced from the immune epitope database (IEDB) undergo conversion into molecular structures. Subsequently, atomic intrinsic informations and inter-atomic connections are extracted and structured as a graph representation. Stacked graph attention and convolution layers comprise the GraphMHC network which classifies bindings. The prediction results from the test set using the GraphMHC model showed a high performance with an area under the receiver operating characteristic curve of 92.2% (91.9-92.5%), surpassing a baseline model. Moreover, by applying the GraphMHC model to melanoma patient data from The Cancer Genome Atlas project, we found a borderline difference (0.061) in overall survival and a significant difference in stromal score between the high and low neoantigen load groups. This distinction was not present in the baseline model. This study presents the first feature-intrinsic method based on biochemical molecular structure for modeling the binding between MHC protein sequences and neoantigen candidate peptide sequences. This model can provide highly accurate responsibility information that can predict the prognosis of immune checkpoint inhibitors to cancer patients who want to apply it.
AB - Neoantigens are tumor-derived peptides and are biomarkers that can predict prognosis related to immune checkpoint inhibition by estimating their binding to major histocompatibility complex (MHC) proteins. Although deep neural networks have been primarily used for these prediction models, it is difficult to interpret the models reported thus far as accurately representing the interactions between biomolecules. In this study, we propose the GraphMHC model, which utilizes a graph neural network model applied to molecular structure to simulate the binding between MHC proteins and peptide sequences. Amino acid sequences sourced from the immune epitope database (IEDB) undergo conversion into molecular structures. Subsequently, atomic intrinsic informations and inter-atomic connections are extracted and structured as a graph representation. Stacked graph attention and convolution layers comprise the GraphMHC network which classifies bindings. The prediction results from the test set using the GraphMHC model showed a high performance with an area under the receiver operating characteristic curve of 92.2% (91.9-92.5%), surpassing a baseline model. Moreover, by applying the GraphMHC model to melanoma patient data from The Cancer Genome Atlas project, we found a borderline difference (0.061) in overall survival and a significant difference in stromal score between the high and low neoantigen load groups. This distinction was not present in the baseline model. This study presents the first feature-intrinsic method based on biochemical molecular structure for modeling the binding between MHC protein sequences and neoantigen candidate peptide sequences. This model can provide highly accurate responsibility information that can predict the prognosis of immune checkpoint inhibitors to cancer patients who want to apply it.
UR - http://www.scopus.com/inward/record.url?scp=85188800035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85188800035&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0291223
DO - 10.1371/journal.pone.0291223
M3 - Article
C2 - 38536842
AN - SCOPUS:85188800035
SN - 1932-6203
VL - 19
JO - PloS one
JF - PloS one
IS - 3 March
M1 - e0291223
ER -