Tracing the evolution of sequencing into the era of genomic medicine

Accelerated discovery in biomedical science is typically punctuated by technological advances, and the past decade has been exemplary regarding breakthroughs in our genomic understanding of human biology in health and disease. This phenomenon was facilitated by the availability of a human genome reference sequence and the development and continuous improvement of next-generation and single-molecule sequencing technologies, accompanied by advances in computational analytics. These fundamental tools have driven the emergence of innovative methods that capture different aspects of human cell biology, with exquisite detail genome wide, in a sequence-based readout. The resulting expansion of knowledge has poised these approaches for clinical adoption, fulfilling the original intention of decoding the human genome and ushering in the era of genomic medicine. Extraordinary advances in genomic science have defined the twenty-first century, transforming our understanding of human biology in both health and disease. This timeline Perspective charts two decades of genomic innovation since the human genome reference sequence became available, highlighting the evolution of sequencing technologies and how they, combined with computational advances, paved the way for genomic medicine.