RESUMO
The allele frequency net database (AFND, http://www.allelefrequencies.net ) is an online web-based repository that contains information on the frequencies of immune-related genes and their corresponding alleles in worldwide human populations. At present, the website contains data from 1784 population samples in more than 14 million individuals from 129 countries on the frequency of genes from different polymorphic regions including data for the human leukocyte antigen (HLA) system. In addition, over the last four years, AFND has also incorporated genotype raw data from 85,000 individuals comprising 215 population samples from 39 countries. Moreover, more population data sets containing next generation sequencing data spanning >3 million individuals have been added. This resource has been widely used in a variety of contexts such as histocompatibility, immunology, epidemiology, pharmacogenetics, epitope prediction algorithms for population coverage in vaccine development, population genetics, among many others. In this chapter, we present an update of the most used searching mechanisms as described in a previous volume and some of the latest developments included in AFND.
Assuntos
Bases de Dados Genéticas , Frequência do Gene , Genética Populacional , Humanos , Genética Populacional/métodos , Antígenos HLA/genética , Alelos , Biologia Computacional/métodos , Internet , Navegador , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Epitopos de Linfócito T/metabolismo , Etnicidade , Antígenos HLA/metabolismo , Proteômica/métodos , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , COVID-19/epidemiologia , Vacinas contra COVID-19 , Doenças Transmissíveis Emergentes , Epitopos de Linfócito T/genética , Antígenos HLA/genética , Humanos , Imunogenicidade da Vacina , Aplicações da Informática Médica , Pandemias/prevenção & controle , Polimorfismo Genético , Ligação Proteica , Software , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
The Allele Frequency Net Database (AFND, www.allelefrequencies.net) provides the scientific community with a freely available repository for the storage of frequency data (alleles, genes, haplotypes and genotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex Class I chain related genes (MIC) and a number of cytokine gene polymorphisms in worldwide populations. In the last five years, AFND has become more popular in terms of clinical and scientific usage, with a recent increase in genotyping data as a necessary component of Short Population Report article submissions to another scientific journal. In addition, we have developed a user-friendly desktop application for HLA and KIR genotype/population data submissions. We have also focused on classification of existing and new data into 'gold-silver-bronze' criteria, allowing users to filter and query depending on their needs. Moreover, we have also continued to expand other features, for example focussed on HLA associations with adverse drug reactions. At present, AFND contains >1600 populations from >10 million healthy individuals, making AFND a valuable resource for the analysis of some of the most polymorphic regions in the human genome.
Assuntos
Citocinas/genética , Bases de Dados Genéticas , Frequência do Gene/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores KIR/genética , Genoma Humano , Humanos , Polimorfismo Genético , Interface Usuário-ComputadorRESUMO
The allele frequency net database (AFND, http://www.allelefrequencies.net ) is an online web-based repository that contains information on the frequencies of immune-related genes and their corresponding alleles in worldwide human populations. At present, the system contains data from 1505 populations in more than ten million individuals on the frequency of genes from different polymorphic regions including data for the human leukocyte antigens (HLA) system. This resource has been widely used in a variety of contexts such as histocompatibility, immunology, epidemiology, pharmacogenetics, and population genetics, among many others. In this chapter, we present some of the more commonly used searching mechanisms and some of the most recent developments included in AFND.