Schena, G. | Search bioRxiv

bioRxiv2024

GeneSqueeze: A Novel Lossless, Reference-Free Compression Algorithm for FASTQ/A Files

As sequencing becomes more accessible, there is an acute need for novel compression methods to efficiently store this data. Omics technologies can enhance biomedical research and individualize patient care, but they demand immense storage capabilities, especially when applied to longitudinal studies. Addressing the storage challenges posed by these technologies is crucial for omics technologies 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 (i.e., nucleotide sequences, quality scores and read identifiers). GeneSqueeze provides several benefits, including an auto-tuning compression protocol based on each samples distribution, lossless preservation of IUPAC nucleotides and read identifiers, and unrestricted FASTQ/A file attributes (i.e., read length, read depth, or read identifier format). We compared GeneSqueeze to the general-purpose compressor, gzip, and to the domain-specific compressor, SPRING. GeneSqueeze achieved up to three times higher compression ratios as compared to gzip, regardless of read length, read depth, or file size. GeneSqueeze achieved 100% lossless compression, with the original and decompressed files perfectly matching for all tested samples, preserving read identifiers, quality scores, and IUPAC nucleotides, in contrast to SPRING. Overall, GeneSqueeze represents a competitive and specialized compression method optimized for FASTQ/A files containing nucleotide sequences that has the potential to significantly reduce the storage and transmission costs associated with large omics datasets without sacrificing data integrity.

bioinformatics↗

bioRxiv2021

The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Approximately 78% of cases are caused by mutations in the PKD1 gene, which encodes polycystin-1 (PC1). PC1 is a large 462-kDa protein that undergoes cleavage in its N and C-terminal domains. C-terminal cleavage produces fragments that translocate to mitochondria. We show that transgenic expression of a protein corresponding to the final 200 amino acid residues of PC1 in a Pkd1-KO orthologous murine model of ADPKD dramatically suppresses cystic phenotype and preserves renal function. This suppression depends upon an interaction between the C-terminal tail of PC1 and the mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase. This interaction modulates tubular/cyst cell proliferation, the metabolic profile, mitochondrial function and the redox state. Together, these results suggest that a short fragment of PC1 is sufficient to suppress cystic phenotype and open the door to the exploration of gene therapy strategies for ADPKD.

physiology↗