Biology subjects

Haddad, N.

Publications and source records attributed to Haddad, N..

5 recordsLinked to original sources

bioRxiv2026

FlavoTyper: a genome-based in-silico serotyping tool for the fish pathogen Flavobacterium psychrophilum

Flavobacterium psychrophilum is a devastating pathogen of fish reared in freshwater worldwide. Serotyping is a relevant method for epidemiological surveillance and outbreak detection, as well as for a better understanding of host-pathogen interactions. Serological diversity may also have important consequences for the selection of appropriate strains for vaccine development and for selective breeding for increased disease resistance. F. psychrophilum serotyping relies on structural variations in the O-polysaccharide (O-PS) moiety of the cell surface lipopolysaccharide (LPS). However, conventional serotyping is costly, labor-intensive and requires significant technical expertise. Moreover, divergent scheme proposals highlighted the absence of harmonization among laboratories. In this context, the development of an mPCR-based serotyping scheme targeting wzy genes greatly improved the reliability and standardization of serotyping. Nevertheless, the proposed mPCR scheme did not capture the entire diversity of genomic variability. The aim of this study was to establish a robust and publicly available tool for F. psychrophilum genome-based serotyping. Extensive genome analysis of the O-antigen biosynthesis locus allowed the identification of biomarkers enabling the development of FlavoTyper, an in-silico-based serotyping tool. The FlavoTyper tool was evaluated on all F. psychrophilum genome assemblies publicly available, providing sound and sensitive predictions and easily interpretable results. When applied to a curated collection of publicly available genomes, the in-silico O-types assigned by the tool were statistically significantly associated with host fish species, confirming previous studies (coho salmon with O:0, rainbow trout with O:1 and O:2, and ayu with O:3) and their distribution across MLST clonal complexes revealed that the O-antigen locus is frequently rearranged independently of the core-genome lineage, consistent with the extensive recombination that shapes the evolution and genomic diversity of this species.

microbiology↗

bioRxiv2023

Evolutionarily diverse origins of honey bee deformed wing viruses

Novel transmission routes can allow infectious diseases to spread, often with devastating consequences. Ectoparasitic varroa mites vector a diversity of RNA viruses and, having switched hosts from the eastern to western honey bees (Apis cerana to Apis mellifera). They provide an opportunity to explore how novel transmission routes shape disease epidemiology. As the principal driver of the spread of Deformed Wing Viruses (mainly DWV-A and DWV-B), varroa infestation has also driven global honey bee health declines. The more virulent DWV-B strain has been replacing the original DWV-A strain in many regions over the past two decades. Yet, how these viruses originated and spread remains poorly understood. Here we use a phylogeographic analysis based on whole genome data to reconstruct the origins and demography of DWV spread. We found that, rather than reemerging in western honey bees after varroa switched hosts, as suggested by previous work, DWV-A most likely originated in Asia and spread in the mid-20th century. It also showed a massive population size expansion following the varroa host switch. By contrast, DWV-B was most likely acquired more recently from a source outside Asia, and appears absent from eastern honey bees, the original varroa host. These results highlight the dynamic nature of viral adaptation, whereby a vectors host switch can give rise to competing and increasingly virulent disease pandemics. The evolutionary novelty and rapid global spread of these host-virus interactions, together with observed spillover into other species, illustrate how increasing globalisation poses urgent threats to biodiversity and food security.

evolutionary biology↗

bioRxiv2019

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection.

Tick-borne encephalitis virus (TBEV) is a member of the Flaviviridae family, Flavivirus genus, which includes several important human pathogens. It is responsible for neurological symptoms that may cause permanent disability or death, and, from a medical point of view, is the major arbovirus in Central/Northern Europe and North-eastern Asia. TBEV tropism is critical for neuropathogenesis, yet, little is known about the molecular mechanisms that govern the susceptibility of human brain cells to the virus. In this study, we sought to establish and characterize a new in vitro model of TBEV infection in the human brain and to decipher cell type-specific innate immunity and its relation to TBEV tropism and neuropathogenesis. We showed that infection of neuronal/glial cultures derived from human fetal neural progenitor cells (hNPCs) mimicked three major hallmarks of TBEV infection in the human brain, namely, preferential neuronal tropism, neuronal death and astrogliosis. We also showed that these cells had conserved their capacity to build an antiviral response against TBEV. TBEV-infected neuronal/glial cells, therefore, represented a highly relevant pathological model. By enriching the cultures in either human neurons or astrocytes, we further demonstrated qualitative and quantitative differential innate immune responses in the two cell types that correlated with their particular susceptibility to TBEV. Our results thus reveal that cell type-specific innate immunity is likely to contribute to shaping TBEV tropism for human brain cells. They offer a new in vitro model to further study TBEV-induced neuropathogenesis and improve our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells.\n\nAuthor summaryTick-borne encephalitis virus (TBEV), a neurotropic Flavivirus that is responsible for encephalitis in humans, is of growing concern in Europe. Indeed, over the last two decades the number of reported cases has continuously increased and the virus has spread into new geographical areas. Whereas it is well established that neurons are the main target of TBEV in the human brain, the mechanisms that underlie this preferential tropism have not yet been elucidated. Here, we used neuronal/glial cells derived from human fetal neural progenitors to establish and characterize a new in vitro pathological model that mimics major hallmarks of TBEV infection in vivo; namely, neuronal tropism, neuronal death and astrogliosis. Using this highly relevant model, we showed that human neurons and astrocytes were both capable of developing an innate immune response against TBEV, but with dissimilar magnitudes that correlated with differential susceptibility to TBEV. Our results thus revealed that TBEV tropism for subsets of human brain cells is likely to depend on cell-type specific innate immunity. This improves our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells and may help guide development of future therapies.

microbiology↗

bioRxiv2019

Butterfly abundance declines over 20 years of systematic monitoring in Ohio, USA

Severe insect declines make headlines, but they are rarely based on systematic monitoring outside of Europe. We estimate the rate of change in total butterfly abundance and the population trends for 81 species using 21 years of systematic monitoring in Ohio, USA. Total abundance is declining at 2% per year, resulting in a cumulative 33% reduction in butterfly abundance. Three times as many species have negative population trends compared to positive trends. The rate of total decline and the proportion of species in decline mirror those documented in three comparable long-term European monitoring programs. Multiple environmental changes such as climate change, habitat degradation, and agricultural practices may contribute to these declines in Ohio and shift the makeup of the butterfly community by benefiting some species over others. Our analysis of life-history traits associated with population trends shows an impact of climate change, as species with northern distributions and fewer annual generations declined more rapidly. However, even common and invasive species associated with human-dominated landscapes are declining, suggesting widespread environmental causes for these trends. Declines in common species, although they may not be close to extinction, will have an outsized impact on the ecosystem services provided by insects. These results from the most extensive, systematic insect monitoring program in North America demonstrate an ongoing defaunation in butterflies that on an annual scale might be imperceptible, but cumulatively has reduced butterfly numbers by a third over 20 years.

ecology↗

bioRxiv2018

Characterizing Subpopulations with Better Response to Treatment Using Observational Data - an Epilepsy Case Study

Electronic health records and health insurance claims, providing observational data on millions of patients, offer great opportunities, and challenges, for population health studies. The objective of this study is identifying subpopulations that are likely to benefit from a given treatment using observational data. We refer to these subpopulations as \"better responders\" and focus on characterizing these using linear scores with a limited number of variables. Building upon well-established causal inference techniques for analyzing observational data, we propose two algorithms that generate such scores for identifying better responders, as well as methods for evaluating and comparing these scores. We applied our methodology to a large dataset of ~135,000 epilepsy patients derived from claims data. Out of this sample, 85,000 were used to characterize subpopulations with better response to next-generation (\"Newer\") anti-epileptic drugs (AEDs), compared to an alternative treatment by first-generation (\"Older\") AEDs. The remaining 50,000 epilepsy patients were then used to evaluate our scores. Our results demonstrate the ability of our scores to identify large subpopulations of epilepsy patients with significantly better response to newer AEDs.

epidemiology↗