Nicole Soranzo | PubMed Health

PubMed2026

COSIGT: population-scalable genotyping of complex loci from low-coverage sequencing data using pangenome graphs.

Pangenome graphs capture extensive structural diversity, but resolving complex loci from shallow sequencing remains challenging, particularly when samples are of low quality such as in ancient DNA. We introduce COSIGT (COsine SImilarity-based GenoTyper), which assigns diploid genotypes by matching read-depth distributions to haplotype paths via cosine similarity. Because this metric evaluates relative coverage profiles rather than absolute read counts, COSIGT substantially outperforms existing likelihood-based tools at low coverage (1-2X). We demonstrate scalability to thousands of modern and ancient genomes, enabling robust, population-scale analyses of complex variation directly from low-coverage datasets.

Humans↗

PubMed2024

eQTLs identify regulatory networks and drivers of variation in the individual response to sepsis.

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.

Humans↗