Advancements in Whole-Genome Sequencing Protocols: A Decade of In-House Operations and Quality Controls at the Tohoku Medical Megabank

Population-scale human whole-genome sequencing (WGS) projects are ongoing worldwide. At a time when such large-scale genome projects were uncommon, the Tohoku Medical Megabank Project initiated genome analysis of the general population in Japan, aiming to build a foundation for personalized medicine and prevention. Recently, we have completed the WGS of 100,000 participants, and research utilizing this genomic foundation is in progress. Early in the project, we realized that standard protocols were not always suitable for large-scale sequencing, necessitating the development of optimized operations and quality control methods. To accommodate various sequencing platforms and adapt protocols to the scale of analysis, we have continuously refined our methods. As multiplex sequencing analysis became standard, we aimed to ensure uniform data quantity across samples. With the advent of large-scale analyses, streamlining operations has also been a critical focus. In this paper, we share the details of our WGS operations and quality control methods developed over a decade, highlighting the unique methods and know-how we have established.