Biology subjects

Nazzal, L.

Publications and source records attributed to Nazzal, L..

2 recordsLinked to original sources

bioRxiv2026

Vritra: gene-specific reference construction for species-resolved functional profiling of metagenomic and metatranscriptomic data

Species-resolved profiling of microbial functional genes is important for linking microbial community composition to biological function, but existing functional profiling approaches are not designed to systematically define user-specified genes and resolve their contributing species. We developed Vritra (Versatile gene-guided Reads-identification with Impartial Taxonomic Refinement and Assignment), a framework for constructing gene-specific reference databases for metagenomic and metatranscriptomic data. Vritra expands and refines the UniRef-based sequence space for user-specified target genes using sequence-similarity network connectivity and functional annotations, retains related homologs as decoys to reduce assignment ambiguity, and links the resulting sequences to standardized microbial taxonomy. Across genes involved in oxalate, urate, and bile acid metabolism, Vritra recovered >97% of sequences represented by established annotation resources for most evaluated genes while substantially expanding the represented sequence space. In real microbiome datasets, the expanded references increased recovery of target-gene reads by up to threefold for poorly annotated genes while maintaining high sequence identity. Application to population-based and publicly available microbiome datasets enabled species-resolved profiling of functional genes and revealed gene-specific associations with microbial taxa, dietary factors, and disease-related phenotypes. Vritra provides a scalable framework for translating continuously expanding sequence resources into gene-specific, species-resolved references for microbiome studies.

bioinformatics↗

bioRxiv2025

Colonization with Oxalobacter formigenes slows the progression of CKD and reduces cardiac remodeling in CKD

Accumulation of oxalate in patients with chronic kidney disease (CKD) is associated with CKD progression and increased risk of cardiac death. Whether reducing plasma or urine oxalate slows CKD progression and prevents cardiovascular complications remains unexplored. We colonized the intestines of control and CKD mice with Oxalobacter formigenes (Oxf), an oxalate-degrading microorganism. The mice were fed with the oxalate precursor hydroxyproline for 23 weeks at which time we assessed pathological changes in the kidney and heart. We demonstrate that Oxf reduces plasma oxalate (pOx) and creatinine levels, mitigates inflammation and fibrosis in the kidney, and reduces pathologic cardiac remodeling in the hearts of CKD mice. RNA-seq analysis of ventricular tissue of CKD mice reveals dysregulated expression of metabolic pathways while Oxf colonization reverses these changes. These findings demonstrate that oxalate accumulation plays a role not only in CKD progression but also in associated cardiovascular complications and suggest that strategies to reduce plasma oxalate levels may have therapeutic benefit. Translational statementChronic kidney disease (CKD) is a major health problem that can lead to kidney failure and which increases the risk of cardiovascular disease (CVD) mortality. Oxalate accumulation in advanced kidney disease contributes to further CKD progression and CVD complications. Intestinal colonization with Oxalobacter formigenes (Oxf) in a CKD animal model reduces plasma oxalate level and slows progression of both CKD and CVD. Strategies to reduce plasma oxalate levels may have therapeutic benefit in the setting of CKD.

microbiology↗