New challenges, new opportunities: Next generation sequencing and its place in the advancement of HLA typing.

The Human Leukocyte Antigen (HLA) system has a critical role in immunorecognition, transplantation, and disease association. Early typing techniques provided the foundation for genotyping methods that revealed HLA as one of the most complex, polymorphic regions of the human genome. Next Generation Sequencing (NGS), the latest molecular technology introduced in clinical tissue typing laboratories, has demonstrated advantages over other established methods. NGS offers high-resolution sequencing of entire genes in time frames and price points considered unthinkable just a few years ago, contributing a wealth of data informing histocompatibility assessment and standards of clinical care. Although the NGS platforms share a high-throughput massively parallel processing model, differing chemistries provide specific strengths and weaknesses. Research-oriented Third Generation Sequencing and related advances in bioengineering continue to broaden the future of NGS in clinical settings. These diverse applications have demanded equally innovative strategies for data management and computational bioinformatics to support and analyze the unprecedented volume and complexity of data generated by NGS. We discuss some of the challenges and opportunities associated with NGS technologies, providing a comprehensive picture of the historical developments that paved the way for the NGS revolution, its current state and future possibilities for HLA typing.