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Biology subjects

Pickett, B.

Publications and source records attributed to Pickett, B..

3 recordsLinked to original sources

Fully Phased Telomere-to-Telomere Assemblies for Thoroughbred Horse and Donkey Haplotypes derived from a Mule Illuminate the Peculiar Evolution of Equid Centromeres

We present telomere-to-telomere genome assemblies of a Thoroughbred horse and a donkey derived from their mule offspring. Now adopted and annotated by NCBI as reference genomes, these assemblies resolve previously inaccessible regions, including satellite arrays, duplications, and telomeres. Equids are known to exhibit an uncoupling between satellite DNA and centromeric function. The completeness of these assemblies enabled annotation of both satellite-based and satellite-free centromeres, as well as non-centromeric satellite loci, revealing notable centromeric plasticity. They also allowed detailed characterization of the variable binding domains of CENP-A--the epigenetic determinant of centromere identity--and CENP-B, whose association with CENP-A, previously considered typical based on a few model organisms, is absent in equids. Comparative analyses of satellite repeats and centromere positions provide new insights into the accelerated karyotypic reshuffling in equid evolution. These assemblies represent foundational resources for equid genomics and support ongoing initiatives such as the Equine Pangenome Project.

molecular biology↗

Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/225581v3_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@15ca5a6org.highwire.dtl.DTLVardef@17f455forg.highwire.dtl.DTLVardef@a39f50org.highwire.dtl.DTLVardef@306ec1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in analog hosts

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable \"heathy ecostate\" communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The \"unhealthy\" ecostates of infected individuals progressed towards the \"healthy ecostate\" over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.\n\nOne Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection

microbiology↗