Biology subjects

Sawyer, C.

Publications and source records attributed to Sawyer, C..

5 recordsLinked to original sources

bioRxiv2026

Description of Alternaria kierstenii sp. nov. from invasive garlic mustard highlights agricultural biosecurity risks of foreign weeds as pathogen reservoirs

Invasive weeds can increase agricultural biosecurity risks by serving as reservoirs for emerging or undercharacterized plant pathogens. Garlic mustard (Alliaria petiolata), an invasive brassicaceous weed in North America, occurs near agricultural landscapes and is susceptible to multiple crop pathogens. A previously undescribed Alternaria species was isolated from a diseased garlic mustard population in Maryland, USA, prompting investigation of its taxonomy, origins, and host range. De novo genome sequencing produced a near-chromosome scale assembly of 35.8 Mb comprising 17 contigs. Comparative genomic analyses with other crucifer-infecting Alternaria species revealed expanded repertoires of predicted CAZymes and peptidases, as well as unique effectors and biosynthetic gene clusters. Phylogenetic and comparative analyses supported recognition of this fungus as Alternaria kierstenii sp. nov., representing a distinct lineage within section Sonchi. Host range assays demonstrated that A. kierstenii was highly aggressive on diverse hosts in the Brassicaceae, including vegetable, ornamental, cover crop, and invasive species. The disease caused by this new pathogen manifested as foliar and stem lesions, chlorosis, necrosis, leaf death, and, in several hosts, rapid plant mortality. Amplicon sequence data from a nationwide garlic mustard microbiome study detected closely related taxa only in the plants from the eastern states of Maryland, Pennsylvania, and New York, suggesting a geographically restricted population consistent with expectations for a potentially emerging pathogen. The description of this phylogenetically unique, broad host range pathogen demonstrates the potential for widespread invasive weeds to harbor pathogens and pathogen genomic diversity with agricultural relevance, underscoring the hidden biosecurity risk of understudied invasive weeds.

microbiology↗

bioRxiv2026

Mobile genetic elements accompany the emergence of clonal crop lineages from weed-associated populations of Xanthomonas campestris

Xanthomonas campestris is a destructive pathogen of cruciferous vegetables and ornamentals and is frequently isolated from related weed species growing near agricultural land. However, the evolutionary relationships, genomic features, and biosecurity significance of weed-associated strains remain poorly understood. Here, we integrate phylogenomic and pangenomic analyses of X. campestris, including nine newly sequenced strains isolated from invasive garlic mustard (Alliaria petiolata), to compare strains from cultivated and non-cultivated hosts across multiple pathovars. Weed-isolated strains predominantly clustered within basal, genetically diverse lineages associated with broad host ranges, whereas crop-isolated strains were concentrated in host-associated clonal lineages. The emergence of specialized crop-associated lineages coincided with multiple inferred acquisitions of large mobile elements, including integrative conjugative and mobilizable elements and plasmids carrying genes previously associated with pathogenicity and host range. Although these elements were enriched in clonal crop-associated lineages, they also occurred in diverse weed-associated strains, indicating that genetic material associated with crop infection is distributed among divergent lineages and persists in wild and weedy systems. These findings identify invasive weeds as ancillary hosts that may harbor pathogen diversity and provide opportunities for genetic exchange, underscoring the importance of surveillance beyond agricultural fields to monitor pathogen diversification and emerging threats. Our pangenomic analysis also identified crop-associated pathogen factors and putative host resistance targets for future investigation, providing a foundation for developing critically needed black rot-resistant cultivars.

microbiology↗

bioRxiv2023

Saturation Genome Editing Resolves the Functional Spectrum of Pathogenic VHL Alleles

To maximize the impact of precision medicine approaches, it is critical to accurately identify genetic variants in cancer-associated genes with functional consequences. Yet, our knowledge of rare variants conferring clinically relevant phenotypes and the mechanisms through which they act remains highly limited. A tumor suppressor gene exemplifying the challenge of variant interpretation is VHL. VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here, we optimize and apply Saturation Genome Editing (SGE) to assay nearly all possible single nucleotide variants (SNVs) across VHLs coding sequence. To delineate mechanisms, we quantify mRNA dosage effects over time and compare effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types, and reveal novel mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered in both germline testing and tumor profiling and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes.

genomics↗

bioRxiv2023

Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults

Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group - broad responders - neutralize a range of SARS-CoV-2 variants, whereas the other - narrow responders - neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.

immunology↗

bioRxiv2021

A systematic benchmark of Nanopore long read RNA sequencing for transcript level analysis in human cell lines

The human genome contains more than 200,000 gene isoforms. However, different isoforms can be highly similar, and with an average length of 1.5kb remain difficult to study with short read sequencing. To systematically evaluate the ability to study the transcriptome at a resolution of individual isoforms we profiled 5 human cell lines with short read cDNA sequencing and Nanopore long read direct RNA, amplification-free direct cDNA, PCR-cDNA sequencing. The long read protocols showed a high level of consistency, with amplification-free RNA and cDNA sequencing being most similar. While short and long reads generated comparable gene expression estimates, they differed substantially for individual isoforms. We find that increased read length improves read-to-transcript assignment, identifies interactions between alternative promoters and splicing, enables the discovery of novel transcripts from repetitive regions, facilitates the quantification of full-length fusion isoforms and enables the simultaneous profiling of m6A RNA modifications when RNA is sequenced directly. Our study demonstrates the advantage of long read RNA sequencing and provides a comprehensive resource that will enable the development and benchmarking of computational methods for profiling complex transcriptional events at isoform-level resolution.

genomics↗