Biology subjects

Flaherty, M.

Publications and source records attributed to Flaherty, M..

3 recordsLinked to original sources

bioRxiv2025

Four Decades of Genomic Stability and Adaptive Divergence in Xanthomonas arboricola pv. pruni-Infecting Phages: Defining Duraznoxanthovirus arenicola and Its Evolutionary Framework

Bacteriophages (phages) are abundant and ecologically significant, yet their diversity and roles in plant-associated ecosystems remain poorly understood, limiting their application in sustainable disease management. To address this gap, we characterized 15 phages infecting Xanthomonas arboricola pv. pruni, the causal agent of bacterial spot on peach, has been isolated for over four decades from North Carolina orchards. Comparative genomic and phylogenetic analyses revealed two temporally distinct clades with >95% nucleotide identity and 63 conserved core genes, forming a new genus and species, Duraznoxanthovirus arenicola. These findings challenge assumptions of pervasive genomic mosaicism, highlighting remarkable genomic stability alongside localized variability in accessory loci. Beyond genus-level characterization, our analyses support a broader taxonomic restructuring within the family Anamaviridae, introducing a new subfamily (Terravirinae) and two new genera (Duraznoxanthovirus and Ralstopathovirus). This work provides the first family-level framework for phages exclusively infecting plant-associated bacteria, offering evolutionary insights and a foundation for ecological studies and management strategies.

microbiology↗

bioRxiv2024

Single-cell genomics and regulatory networks for 388 human brains

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized [~]250 disease-risk genes and drug targets with associated cell types. Summary Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/585576v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@70b24org.highwire.dtl.DTLVardef@6c9eddorg.highwire.dtl.DTLVardef@131fae2org.highwire.dtl.DTLVardef@4e0f1e_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2024

Validation of Enhancer Regions in Primary Human Neural Progenitor Cells using Capture STARR-seq

Genome-wide association studies (GWAS) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. We performed capture STARR-sequencing of over 78,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We selected candidate regions by integrating data from NPCs, prefrontal cortex, developmental timepoints, and GWAS. Over 8,000 regions demonstrated enhancer activity in the phNPCs, and we linked these regions to over 2,200 predicted target genes. These genes are involved in neuronal and psychiatric disease-associated pathways, including dopaminergic synapse, axon guidance, and schizophrenia. We functionally validated a subset of these enhancers using mutation STARR-sequencing and CRISPR deletions, demonstrating the effects of genetic variation on enhancer activity and enhancer deletion on gene expression. Overall, we identified thousands of highly active enhancers and functionally validated a subset of these enhancers, improving our understanding of regulatory networks underlying brain function and disease.

neuroscience↗