Note that CRAM format does use the reference genome to compress sequences. http://www.1000genomes.org/faq/what-are-cram-files http://www.1000genomes.org/faq/wh

Note that CRAM format does use the reference genome to compress sequences. http://www.1000genomes.org/faq/what-are-cram-files http://www.1000genomes.org/faq/what-are-cram-files CRAM files are alignment files like BAM files. They represent a compressed version of the alignment. This compression is driven by the reference the sequence data is aligned to. Benchmarks here : http://www.htslib.org/benchmarks/CRAM.html http://www.htslib.org/benchmarks/CRAM.html