Biology subjects

Garza, J. E.

Publications and source records attributed to Garza, J. E..

3 recordsLinked to original sources

bioRxiv2026

Leveraging Human Pangenome for Improved Somatic Variant Detection

Somatic variant detection is technically challenging due to low variant allele fractions, the confounding presence of germline variation, and reference bias. Linear references such as GRCh38 miss sample-specific variation, causing misalignments and incorrect variant calls. Although telomere-to-telomere donor-specific assemblies (DSAs) accurately represent individual genomes, their application is limited by cost and technical barriers. Alternatively, the graph-based human pangenome provides a scalable framework to improve read alignment and perform genome inference. Here, we benchmarked somatic variant detection using GRCh38, graph-based pangenomes, and pangenome-inferred DSAs with a HapMap mixture dataset and the COLO829 melanoma cell line. Pangenome-guided alignment improves read mapping and somatic variant calling accuracy. Furthermore, personalized pangenomes partially reconstruct donor-specific genomic content, improving accuracy, reducing germline contamination, and enabling detection of events in loci absent or poorly represented in GRCh38. These findings demonstrate that graph-based and personalized pangenomes are effective strategies for enhancing somatic variant detection compared with GRCh38.

genomics↗

bioRxiv2025

The Vaginal Microbiome in Women Recently Experiencing BV and UTI

The vaginal microbiome (VMB) influences susceptibility to urogenital infections, yet large-scale, population-based species-level metagenomic studies are rare. We analyzed cross-sectional shotgun metagenomic profiles and linked clinical metadata from 10,003 women across the United States who self-reported recent bacterial vaginosis (BV), urinary tract infection (UTI), both, or neither. Women reporting recent BV or UTI displayed distinct community structures, including higher prevalence of VALENCIA CST-IV subtypes and significantly elevated alpha diversity compared with women who reported no prior diagnosis. Species-level Gardnerella profiling revealed that multiple Gardnerella species were enriched in the recent BV group but did not differ significantly between UTI and non-UTI groups, refining prior mechanistic hypotheses. Uropathogens such as E. coli, E. faecalis, and S. saprophyticus were detectable at higher prevalence and relative abundance in women who recently experienced UTI, including among participants who reported recent antibiotic use, consistent with the possibility of residual or recurrent vaginal colonization. These findings demonstrate that microbial signatures associated with recent BV and UTI remain detectable at population scale, provide a high-resolution reference for human vaginal metagenomics, and offer new directions for prevention strategies that consider the vaginal reservoir in recurrent urogenital infections.

microbiology↗

bioRxiv2025

A Pangenomic Method for Establishing a Somatic Variant Detection Resource in HapMap Mixtures

Somatic mosaicism is essential in human biology and disease, yet robust benchmarks are scarce. The SMaHT Consortium mixed six HapMap cell lines to create artificial somatic variants spanning 0.25% to 16.5% variant allele fractions. We developed a technology-agnostic method that builds pangenome graphs from individual assemblies to create unified benchmarking sets: > 6M single-nucleotide variants, 1.8M small insertions/deletions, 49K structural variations, and 10K mobile element insertions across autosomes, X, and mitochondrial chromosomes. We validated the variants using ultra-deep simulated reads and developed a binomial-based model to estimate coverage requirements for variant detection. Evaluating multiple callers showed CHM13 alignment improves structural variant detection and offers advantages in difficult-to-map regions compared to GRCh38. Systematic characterization showed regions with low detection rate are enriched in centromeres, satellite sequences, tandem repeats, and falsely duplicated genes. This accurate, versatile resource enables systematic evaluation of somatic variant detection technologies.

genomics↗