Lossless and reference-free compression of FASTQ/A files using GeneSqueeze

Abstract

As sequencing becomes more accessible, there is an acute need for novel compression methods to efficiently store sequencing files. Omics analytics can leverage sequencing technologies to enhance biomedical research and individualize patient care, but sequencing files demand immense storage capabilities, particularly when sequencing is utilized for longitudinal studies. Addressing the storage challenges posed by these technologies is crucial for omics analytics to achieve their full potential. We present a novel lossless, reference-free compression algorithm, GeneSqueeze, that leverages the patterns inherent in the underlying components of FASTQ files to solve this need. GeneSqueeze's benefits include an auto-tuning compression protocol based on each file's distribution, lossless preservation of IUPAC nucleotides and read identifiers, and unrestricted FASTQ/A file attributes (i.e., read length, number of reads, or read identifier format). We compared GeneSqueeze to the general-purpose compressor, gzip, and to a domain-specific compressor, SPRING, to assess performance. Due to GeneSqueeze's current Python implementation, GeneSqueeze underperformed as compared to gzip and SPRING in the time domain. GeneSqueeze and gzip achieved 100% lossless compression across all elements of the FASTQ files (i.e. the read identifier, sequence, quality score and ' + ' lines). GeneSqueeze and gzip compressed all files losslessly, while both SPRING's traditional and lossless modes exhibited data loss of non-ACGTN IUPAC nucleotides and of metadata following the ' + ' on the separator line. GeneSqueeze showed up to three times higher compression ratios as compared to gzip, regardless of read length, number of reads, or file size, and had comparable compression ratios to SPRING across a variety of factors. Overall, GeneSqueeze represents a competitive and specialized compression method for FASTQ/A files containing nucleotide sequences. As such, GeneSqueeze has the potential to significantly reduce the storage and transmission costs associated with large omics datasets without sacrificing data integrity.

Keywords: k-mer sequence; DNA; FASTA; FASTQ; Genomic data compression; Lossless compression; Next-generation sequencing; RNA; Storage.