The avalanche of easy-to-create genomics data has impacted almost all areas of medicine and science, from cancer patients and microbial diagnostics to molecular monitoring for astronauts in space. Recent technologies and algorithms from our laboratory and others can now show single-cell and clonal resolution of phenotypes as they evolve and resist therapies, which manifest at the genome, epigenome, transcriptome, and epitranscriptome levels.  To contextualize these molecular dynamics, we are piloting new methods across the central dogma (DNA, RNA, protein), including an integrative, cross-kingdom view of patients (precision metagenomics) and global citizen science projects that leverage longitudinal metagenome and microbiome profiles of the world’s urban systems (MetaSUB.org) to map global dynamics of antimicrobial resistance (AMR) markers.  All of these methods and molecular tools work together to guide the most comprehensive, longitudinal, mutli-omic view of human astronaut physiology in the NASA Twins Study and the NASA Biomolecule Sequencer Mission, creating new technologies that can sequence, quantify, and engineer nucleic acids and entire genomes for long-term human space travel.