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Biology subjects

Webster, B.

Publications and source records attributed to Webster, B..

4 recordsLinked to original sources

Predicting complex phenotypes using multi-omics data in maize

Understanding and predicting complex traits in plants remains a fundamental challenge due to the emergent nature of most phenotypes and their dependence on genetic, regulatory, and environmental interactions. Accurate prediction of traits and identification of underlying genetic elements has broad applications for plant breeding, systems biology, and biotechnology. Here, we tested if multi-omic datasets could improve predictive accuracy of 129 diverse maize phenotypes across nine environments using genomic markers, field based transcriptomic data from two locations, and drone-derived phenomic data of vegetative indices. We trained and compared linear (rrBLUP) and nonlinear (support vector regression) models using single- and multi-omics inputs. Multi-omics models consistently outperformed single-omics models for most traits, with genomic and transcriptomic inputs contributing distinct biological features. Phenomic features alone yielded the lowest predictive power but improved predictions for specific trait categories like root architecture. Transcriptomic datasets enabled cross-environment prediction, demonstrating that gene expression patterns from one field site could accurately predict traits measured in another. Environment-specific expression of benchmark flowering time genes highlighted the value of transcriptomics in capturing genotype-by-environment (GxE) interactions not detectable through genomic data alone. These findings demonstrate that integrating transcriptomic and phenomic data with genotypes enhances trait prediction, improves model generalizability across environments, and provides deeper insight into the genetic and regulatory architecture of agriculturally important traits in maize.

plant biology↗

Genomic data reveal a north-south split and introgression history of blood fluke (Schistosoma haematobium) populations from across Africa

The human parasitic fluke, Schistosoma haematobium hybridizes with the livestock parasite S. bovis in the laboratory, but the frequency of hybridization in nature is unclear. We analyzed 34.6 million single nucleotide variants in 162 samples from 18 African countries, revealing a sharp genetic discontinuity between northern and southern S. haematobium. We found no evidence for recent hybridization. Instead the data reveal admixture events that occurred 257-879 generations ago in northern S. haematobium populations. Fifteen introgressed S. bovis genes are approaching fixation in northern S. haematobium with four genes potentially driving adaptation. We identified 19 regions that were resistant to introgression; these were enriched on the sex chromosomes. These results (i) suggest strong barriers to gene flow between these species, (ii) indicate that hybridization may be less common than currently envisaged, but (iii) reveal profound genomic consequences of rare interspecific hybridization between schistosomes of medical and veterinary importance.

evolutionary biology↗

Combinatorial CRISPR screens and lectin microarrays identify novel glycosylation regulators

Glycans play critical roles in cellular signaling and function. Unlike proteins, glycan structures are not templated from genes but the concerted activity of many genes, making them historically challenging to study. Here, we present a strategy that utilizes pooled CRISPR screens and lectin microarrays to uncover and characterize regulators of cell surface glycosylation. We applied this approach to study the regulation of high mannose glycans - the starting structure of all asparagine(N)-linked-glycans. We used CRISPR screens to uncover the expanded network of genes controlling high mannose surface levels, followed by lectin microarrays to fully measure the complex effect of select regulators on glycosylation globally. Through this, we elucidated how two novel high mannose regulators - TM9SF3 and the CCC complex - control complex N-glycosylation via regulating Golgi morphology and function. Notably, this method allowed us to interrogate Golgi function in-depth and reveal that similar disruption to Golgi morphology can lead to drastically different glycosylation outcomes. Collectively, this work demonstrates a generalizable approach for systematically dissecting the regulatory network underlying glycosylation.

cell biology↗

Antiviral Response by Plasmacytoid Dendritic Cells via Interferogenic Synapse with Infected Cells

Type I interferon (IFN-I) is critical for protection against viral infections. Plasmacytoid dendritic cells (pDCs) massively produce IFN-I against viruses. Physical contacts are required for pDC-mediated sensing of cells infected by genetically distant viruses. How and why these contacts are established remains enigmatic. Using dengue, hepatitis C, zika viruses, we demonstrate that the pDC/infected cell interface is a specialized platform for viral immunostimulatory-RNA transfer, which we named interferogenic synapse and required for pDC-mediated antiviral response. This synapse is an exquisitely differentiated territory with polarized adhesion complexes and regulators of actin network and endocytosis. Toll-like receptor 7-induced signaling in pDCs promotes the interferogenic synapse establishment, thus providing a feed-forward regulation that sustains contacts with infected cells. We propose that the interferogenic synapse is crucial to pDC function as it allows scanning of infected cells to locally secrete IFN-I at the infection site, thereby confining a response potentially deleterious to the host.\n\nHighlightsO_LIpDCs adhere to infected cells via L{beta}2 integrin/ICAM-1\nC_LIO_LIRegulators of actin network and endocytosis polarize at contact\nC_LIO_LITLR7-induced signaling potentiates pDC polarity\nC_LIO_LIInfected cells activate pDCs by interferogenic synapse\nC_LI

microbiology↗