Understanding how structural mutations and individual RNA isoforms are involved in human health and disease

In today’s efforts to personalize medicine, it does not seem reasonable to personalize medicine without understanding the nuances of individual RNA and protein isoforms across the human genome. Despite the central dogma of biology having been established for decades, major gaps in our understanding remain, including why human protein-coding genes average eight RNA isoforms, resulting in many unique protein products. Given the complexity of human biology, with potentially up to 400 unique major cell types and a vast range of developmental and aging stages, it seems unlikely that a mere 20,000+ protein-coding genes all performing a single function could enable such remarkable complexity. A next critical step in all of biology research, especially in human health and disease research, will be to determine individual isoform function. Some of these differences may be subtle, but may explain many of the subtleties we observe in human health (e.g., sex differences, response to vaccines, drug treatments, disease development & progression, complex traits, etc.). For practical reasons, standard short-read RNA sequencing studies treat all isoforms as a single ‘gene’—an oversimplification of the underlying biology. We want to help determine what purpose individual RNA and protein isoforms play in human health and disease, and are employing long-read sequencing technologies to accomplish these goals.