Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools

Abstract

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.

Design of a Companion Bioinformatic Tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

“…By inspecting RBD variants in 12 countries, a few events, such as Furthermore, we explored whether these RBD mutations were influencing the class 1 presentation of SARS-CoV-2 epitopes. From the top five mutations at 0.1% frequency, we performed MHC class 1 binding prediction with NetMHC4 [15] , for both the wild-type (Wuhan strain) and the mutated strain, choosing the most frequent HLAs in public databases [16] . The software generated predictions for all possible 9-mers resulting from the full RBD sequence, and we computed how binders where calculated for all the considered HLAs.…”

Prioritization of SARS-CoV-2 epitopes using a pan-HLA and global population inference approach

“…Population frequencies of HLA alleles were obtained from the Allele Frequency Net Database (Gonzalez-Galarza et al, 2020). The database contains HLA Frequency data for Class I and Class II alleles across 1,028 distinct populations.…”

Characterization of SARS-CoV-2 viral diversity within and across hosts

“…We first applied MHCflurry (O'Donnell et al, 2018) to compute the HLA/MHC-I peptide specificity of all mutational positions and counted the number of strong binders with predicted IC50 ≤ 500 nM for each HLA allele. Then we approximated the immunogenicity of a sample by taking the average of the count of binders for all HLA allele types weighted by the HLA frequencies of the country where the sample is from (Gonzalez-Galarza et al, 2019). We performed the immunogenicity comparison at the clade level in four major countries (USA, UK, Australia and the Netherlands) with the most GISAID sequences and focused on the clades with at least 50 samples.…”

“…Specifically, we downloaded population HLA allele frequencies of countries from the Allele Frequency Net Database (Gonzalez-Galarza et al, 2019). If an allele has several frequencies available from different studies, we took the mean value as its frequency.…”