To interpret genome sequence from telomere to telomere, it is helpful end-to-end haplotypes with single-molecule epigenetics overlays, via in situ omics at sub-cellular (20 nm) resolution and multicellular (connectome) context. To test putative causative alleles and therapies, we need faithfully representative organoids and accurate editing of these (not merely NHEJ knockouts). We also benefit from comprehensive precision medicine datasets on individuals broadly shareable by virtue of either "open consent" protocols (personalgenomes.org) or provably secure queries via homomorphic encryption and blockchain (Nebula.org). This goals are aided by recent reduction in cost of human and environmental DNA sequencing by over 10 million fold and new editing tools capable of over 26,000 edits per cell (including tools to read, alter and test changes in DNA repeats).
1. New technologies -- In situ & Nanopore sequencing are moving us toward portable, real-time, inexpensive (0-$999) & gap-less clinical-grade genomes.
2. Interpretation benefits from testing variants in organoids & large shareable cohorts – enabled by either open consent or secure via homomorphic encryption queries & blockchain public ledgers.