From graph models to intelligent decision-making: a review of spatio-temporal graph neural networks for regional disease risk prediction and etiology mining.

The human major histocompatibility complex (MHC) was discovered over 50 years ago, also referred to as HLA, and initially gained prominence for its role in transplantation and histocompatibility antigens. Extensive research has illuminated the complex genomic makeup of the MHC, revealing how genetic variance within this region significantly impacts susceptibility to autoimmune, infectious, and diverse diseases. With high gene density and polymorphism, the MHC presents a challenging interplay of genetic diversity with profound functional consequences. Despite the complexities of its diversity, significant insights have emerged, establishing the MHC as a foundational element in human genomics (–). The MHC in humans, located on chromosome 6, is a region of the genome pivotal for immune function and self-recognition. It encodes a diverse set of genes responsible for the production HLAs, which play a crucial role in antigen presentation to T cells. The MHC is divided into two main classes, Class I and Class II. Class I molecules, including HLA-A, HLA-B, and HLA-C, are expressed on nearly all nucleated cells and present intracellular antigens to cytotoxic T cells (–). MHC class II molecules hold a critical position within the immune system, playing a pivotal role in combating infections and serving as a primary concern in the field of transplantation medicine. These molecules not only present antigenic peptides sourced mainly from extracellular origins to CD4+ T cells but also facilitate the crucial process of thymic selection for helper T cells. Comprising an α and β chain, MHC class II molecules are guided to endosomal-lysosomal compartments by the invariant chain, ensuring their proper function in antigen presentation and immune response modulation. Class II molecules, such as HLA-DP, HLA-DQ, and HLA-DR, are primarily found on antigen-presenting cells and present extracellular antigens to helper T cells. The extreme polymorphism of HLA genes within the MHC is a hallmark of the complex, allowing for a vast array of antigen presentation capabilities crucial for immune surveillance and response (–). The MHC significance extends beyond immune responses, playing a key role in various diseases, including autoimmune disorders, infectious diseases, and transplantation outcomes. The diversity of HLA alleles within the MHC poses challenges in transplantation matching, as mismatched HLA types can lead to graft rejection. In autoimmune diseases, associations with specific HLA alleles shed light on genetic predispositions and immune dysregulation. Furthermore, the MHC involvement in infectious diseases is highlighted by its role in shaping individual immune responses to pathogens. HLA class I and class II antigens exhibit remarkable polymorphism in their structural genes, making them one of the most diverse gene families in humans. This extensive genetic diversity results in minor variations in amino acids within each HLA molecule among individuals. Such variability gives rise to a wide array of unique HLA types, contributing to the complexity of the human immune system (–). The HLA is an important component of the immune system, have a significant role in autoimmune diseases, there is often a dysregulation in the recognition of self from non-self-antigens, leading to an immune attack on the body’s own tissues. Specific HLA alleles have been associated with an increased risk of developing various autoimmune diseases. For example, certain HLA alleles are linked to autoimmune conditions such as type 1 diabetes, rheumatoid arthritis, and celiac disease. The interactions between HLA molecules and self-antigens can trigger an immune response against the body’s own tissues, contributing to the pathogenesis of autoimmune diseases (–).