I strongly agree with the idea of deconstructing legacy files (BAM, VCF, etc.) and moving to an API-centric (vs. file-format-centric) world. The Global Alliance for Genomics and Health (GA4GH.org) is working on that, with good early success -- for example, IGV (genome browser) can now work with either files or standard APIs, as can Picard (one of the popular suites of genome analysis tools). See <a href="https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=d8EvXtz2uiA" rel="nofollow">https:&#x2F;&#x2F;www.youtube.com&#x2F;watch?v=d8EvXtz2uiA</a> for details on the Picard support.<p>Disclaimer: I work on Google Genomics, and on the GA4GH APIs.