RESUMO
MOTIVATION: In silico identification of linear B-cell epitopes represents an important step in the development of diagnostic tests and vaccine candidates, by providing potential high-probability targets for experimental investigation. Current predictive tools were developed under a generalist approach, training models with heterogeneous datasets to develop predictors that can be deployed for a wide variety of pathogens. However, continuous advances in processing power and the increasing amount of epitope data for a broad range of pathogens indicate that training organism or taxon-specific models may become a feasible alternative, with unexplored potential gains in predictive performance. RESULTS: This article shows how organism-specific training of epitope prediction models can yield substantial performance gains across several quality metrics when compared to models trained with heterogeneous and hybrid data, and with a variety of widely used predictors from the literature. These results suggest a promising alternative for the development of custom-tailored predictive models with high predictive power, which can be easily implemented and deployed for the investigation of specific pathogens. AVAILABILITY AND IMPLEMENTATION: The data underlying this article, as well as the full reproducibility scripts, are available at https://github.com/fcampelo/OrgSpec-paper. The R package that implements the organism-specific pipeline functions is available at https://github.com/fcampelo/epitopes. SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.
Assuntos
Mapeamento de Epitopos , Epitopos de Linfócito B , Aprendizado de Máquina , Análise de Sequência de Proteína , Humanos , Animais , Conjuntos de Dados como Assunto , Especificidade da Espécie , Análise de Sequência de Proteína/métodos , Mapeamento de Epitopos/métodosRESUMO
Tambaqui (Colossoma macropomum) is the major native species in Brazilian aquaculture, and we have shown that females exhibit a higher growth compared to males, opening up the possibility for the production of all-female population. To date, there is no information on the sex determination and differentiation molecular mechanisms of tambaqui. In the present study, transcriptome sequencing of juvenile trunks was performed to understand the molecular network involved in the gonadal sex differentiation. The results showed that before differentiation, components of the Wnt/ß-catenin pathway, fox and fst genes imprint female sex development, whereas antagonistic pathways (gsk3b, wt1 and fgfr2), sox9 and genes for androgen synthesis indicate male differentiation. Hence, in undifferentiated tambaqui, the Wnt/ß-catenin exerts a role on sex differentiation, either upregulated in female-like individuals, or antagonized in male-like individuals.
Assuntos
Caraciformes/crescimento & desenvolvimento , Ovário/metabolismo , Diferenciação Sexual/genética , Testículo/metabolismo , Animais , Vias Biossintéticas/genética , Caraciformes/genética , Caraciformes/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Masculino , Ovário/anatomia & histologia , Ovário/crescimento & desenvolvimento , Testículo/anatomia & histologia , Testículo/crescimento & desenvolvimento , Transcriptoma , Via de Sinalização WntRESUMO
The emergence of highly contagious and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has required reformulation of coronavirus disease 2019 (COVID-19) vaccines to target those new variants specifically. While previous infections and booster vaccinations can enhance variant neutralization, it is unclear whether the monovalent version, administered using either mRNA or protein-based vaccine platforms, can elicit de novo B-cell responses specific for Omicron XBB.1.5 variants. Here, we dissected the genetic antibody repertoire of 603 individual plasmablasts derived from five individuals who received a monovalent XBB.1.5 vaccination either with mRNA (Moderna or Pfizer/BioNtech) or adjuvanted protein (Novavax). From these sequences, we expressed 100 human monoclonal antibodies and determined binding, affinity and protective potential against several SARS-CoV-2 variants, including JN.1. We then select two vaccine-induced XBB.1.5 mAbs, M2 and M39. M2 mAb was a de novo, antibody, i.e., specific for XBB.1.5 but not ancestral SARS-CoV-2. M39 bound and neutralized both XBB.1.5 and JN.1 strains. Our high-resolution cryo-electron microscopy (EM) structures of M2 and M39 in complex with the XBB.1.5 spike glycoprotein defined the epitopes engaged and revealed the molecular determinants for the mAbs' specificity. These data show, at the molecular level, that monovalent, variant-specific vaccines can elicit functional antibodies, and shed light on potential functional and genetic differences of mAbs induced by vaccinations with different vaccine platforms.\.