Understanding and Therapeutic Application of Immune Response in Major Histocompatibility Complex (MHC) Diversity Using Multimodal Artificial Intelligence

Abstract

Human Leukocyte Antigen (HLA) is like a device that monitors the internal environment of the body. T lymphocytes immediately recognize the HLA molecules that are expressed on the surface of the cells of the different individual, attacking it defeats microorganisms that is one of the causes of rejection in organ transplants performed between people with unmatched HLA types. Over 2850 and 3580 different polymorphisms have been reported for HLA-A and HLA-B respectively, around the world. HLA genes are associated with the risk of developing a variety of diseases, including autoimmune diseases, and play an important role in pathological conditions. By using a deep learning method called multi-task learning to simultaneously predict the gene sequences of multiple HLA genes, it is possible to improve accuracy and shorten execution time. Some new systems use a model called convolutional neural network (CNNs) in deep learning, which uses neural networks consisting of many layers and can learn complex correlations between SNP information and HLA gene sequences based on reference data for HLA imputation, which serves as training data. The learned model can output predicted values of HLA gene sequences with high accuracy using SNP information as input. To investigate which part of the input information surrounding the HLA gene is used to make learning predictions, predictions were made using not only a small number of nearby SNP information but also many SNP information distributed over a wider area by visualizing the learning information of the model. While conventional methods are strong at learning using nearly SNP information and not good at learning using SNP information located at distant locations, some new systems are thought that prediction accuracy may have improved because this problem was overcome. HLA genes are involved in the onset of a variety of diseases and are attracting attention. As an important area from the perspective of elucidating pathological conditions and realizing personalized medicine. The applied multi-task learning to two different HLA imputation reference panels—a Japanese panel (n = 1118) and type I diabetes genetics consortium panel (n = 5122). Through 10-fold cross-validation on these panels, the multi-task learning achieved higher imputation accuracy than conventional methods, especially for imputing low-frequency and rare HLA alleles. The increased prediction accuracy of HLA gene sequences is expected to increase the reliability of HLA analysis, including integrated analysis between different racial populations, and is expected to greatly contribute to the identification of HLA gene sequences associated with diseases and further elucidation of pathological conditions.