Retrospective data analyses unlock genomics technology development

Later this decade, it’s estimated that humanity will have collectively sequenced more than one zettabase of DNA (10^21 nucleotides). Here, I describe three vignettes from our lab that show how critical re-examination of this vast amount of DNA sequencing data can uncover novel biological associations. As our retrospective analyses are imperfectly controlled, I outline our rationale for developing new technologies that corroborate insights from these data-driven explorations. First, I will show how retrospective analyses of human mitochondrial DNA nucleotides enable clonal lineage tracing from human samples and how modified commercial chemistries for single-cell sequencing can facilitate high-resolution clonal lineages from native human tissues. Next, I will describe our work examining viral nucleic acids from existing sequencing libraries, particularly our characterization of HHV-6 reactivation in T cell therapies, and how this discovery shaped our development of new tools for nucleic acid cytometry. Finally, I will preview our lab’s forthcoming work on endemic DNA viruses in the human blood virome that may serve as a novel biomarker of complex disease.