biostudies-literatureUnknown21(2)Sha CMSepsis is a life-threatening state of disseminated infection, and treatment requires knowledge of the organism responsible. The gold standard for sepsis diagnosis is blood culture, which requires days of growth. Next-generation sequencing has been proposed as an alternative; however, existing methods may lack sensitivity. In this work, we explore the idea of genomic quasi-G-primes, which are short DNA sequences specific to a single species within a group of relevant species. We first validated the genomic quasi-G-prime classification in controlled Staphylococcus aureus sequencing experiments, and then applied the same approach to blood-derived sequencing data from septic and healthy patients, where genomic quasi-G-prime profiles distinguished disease states. Our method is highly space-effiPloS onee0341828https://www.ebi.ac.uk/biostudies/studies/S-EPMC12880686biostudies-literatureDoing more with less: Genomic quasi-G-primes differentiate septic from healthy patients.PMC12880686Patsakis MChung TSha CMMouratidis IKovac JWei XGeorgakopoulos-Soares IfalseDoing more with less: Genomic quasi-G-primes differentiate septic from healthy patients.Sepsis is a life-threatening state of disseminated infection, and treatment requires knowledge of the organism responsible. The gold standard for sepsis diagnosis is blood culture, which requires days of growth. Next-generation sequencing has been proposed as an alternative; however, existing methods may lack sensitivity. In this work, we explore the idea of genomic quasi-G-primes, which are short DNA sequences specific to a single species within a group of relevant species. We first validated the genomic quasi-G-prime classification in controlled Staphylococcus aureus sequencing experiments, and then applied the same approach to blood-derived sequencing data from septic and healthy patients, where genomic quasi-G-prime profiles distinguished disease states. Our method is highly space-effi2026-01-01T00:00:00Z20262026-07-15T06:15:08.104Z2026-06-30T03:21:24.44ZS-EPMC128806864165012310.1371/journal.pone.0341828