RT Journal Article SR Electronic T1 CRAM 3.1: Advances in the CRAM File Format JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.15.460485 DO 10.1101/2021.09.15.460485 A1 James K Bonfield YR 2021 UL http://biorxiv.org/content/early/2021/10/11/2021.09.15.460485.abstract AB Motivation CRAM has established itself as a high compression alternative to the BAM file format for DNA sequencing data. We describe updates to further improve this on modern sequencing instruments.Results With Illumina data CRAM 3.1 is 7 to 15% smaller than the equivalent CRAM 3.0 file, and 50 to 70% smaller than the corresponding BAM file. Long-read technology shows more modest compression due to the presence of high-entropy signals.Availability The CRAM 3.0 specification is freely available from https://samtools.github.io/hts-specs/CRAMv3.pdf. The CRAM 3.1 improvements are available from https://github.com/samtools/hts-specs/pull/433, with OpenSource implementations in HTSlib and HTScodecs.Contact jkb{at}sanger.ac.ukSupplementary information Supplementary data are available onlineCompeting Interest StatementThe authors have declared no competing interest.