TY - JOUR
T1 - Binding peptide generation for MHC Class I proteins with deep reinforcement learning
AU - Chen, Ziqi
AU - Zhang, Baoyi
AU - Guo, Hongyu
AU - Emani, Prashant
AU - Clancy, Trevor
AU - Jiang, Chongming
AU - Gerstein, Mark
AU - Ning, Xia
AU - Cheng, Chao
AU - Min, Martin Renqiang
N1 - Funding Information:
This work was made possible, in part, by support from the National Science Foundation grant no. IIS-2133650 (X.N. and Z.C.) and NEC Laboratories America. Any opinions, findings and conclusions or recommendations expressed in this paper are those of the authors and do not necessarily reflect the views of the funding agencies. Part of this work was done when the first author was an intern at NEC Laboratories America.
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Motivation: MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of peptides for various MHC Class I proteins are distinct, which can be reflected by their diverse binding motifs. To characterize binding motifs for MHC Class I proteins, in vitro experiments have been conducted to screen peptides with high binding affinities to hundreds of given MHC Class I proteins. However, considering tens of thousands of known MHC Class I proteins, conducting in vitro experiments for extensive MHC proteins is infeasible, and thus a more efficient and scalable way to characterize binding motifs is needed. Results: We presented a de novo generation framework, coined PepPPO, to characterize binding motif for any given MHC Class I proteins via generating repertoires of peptides presented by them. PepPPO leverages a reinforcement learning agent with a mutation policy to mutate random input peptides into positive presented ones. Using PepPPO, we characterized binding motifs for around 10 000 known human MHC Class I proteins with and without experimental data. These computed motifs demonstrated high similarities with those derived from experimental data. In addition, we found that the motifs could be used for the rapid screening of neoantigens at a much lower time cost than previous deep-learning methods.
AB - Motivation: MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of peptides for various MHC Class I proteins are distinct, which can be reflected by their diverse binding motifs. To characterize binding motifs for MHC Class I proteins, in vitro experiments have been conducted to screen peptides with high binding affinities to hundreds of given MHC Class I proteins. However, considering tens of thousands of known MHC Class I proteins, conducting in vitro experiments for extensive MHC proteins is infeasible, and thus a more efficient and scalable way to characterize binding motifs is needed. Results: We presented a de novo generation framework, coined PepPPO, to characterize binding motif for any given MHC Class I proteins via generating repertoires of peptides presented by them. PepPPO leverages a reinforcement learning agent with a mutation policy to mutate random input peptides into positive presented ones. Using PepPPO, we characterized binding motifs for around 10 000 known human MHC Class I proteins with and without experimental data. These computed motifs demonstrated high similarities with those derived from experimental data. In addition, we found that the motifs could be used for the rapid screening of neoantigens at a much lower time cost than previous deep-learning methods.
UR - http://www.scopus.com/inward/record.url?scp=85147783665&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/btad055
DO - 10.1093/bioinformatics/btad055
M3 - Article
C2 - 36692135
AN - SCOPUS:85147783665
SN - 1367-4803
VL - 39
JO - Bioinformatics
JF - Bioinformatics
IS - 2
M1 - btad055
ER -