PGSbuilder: An end-to-end platform for human genome association analysis and polygenic risk score predictions

Abstract

Understanding the genetic basis of human complex diseases is increasingly important in the development of precision medicine. Over the last decade, genome-wide association studies (GWAS) have become a key technique for detecting associations between common diseases and single nucleotide polymorphisms (SNPs) present in a cohort of individuals. Alternatively, the polygenic risk score (PRS), which often applies results from GWAS summary statistics, is calculated for the estimation of genetic propensity to a trait at the individual level. Despite many GWAS and PRS tools being available to analyze a large volume of genotype data, most clinicians and medical researchers are often not familiar with the bioinformatics tools and lack access to a high-performance computing cluster resource. To fill this gap, we provide a publicly available web server, PGSbuilder, for the GWAS and PRS analysis of human genomes with variant annotations. The user-friendly and intuitive PGSbuilder web server is developed to facilitate the discovery of the genetic variants associated with complex traits and diseases for medical professionals with limited computational skills. For GWAS analysis, PGSbuilder provides the most renowned analysis tool PLINK 2.0 package. For PRS, PGSbuilder provides six different PRS methods including Clumping and Thresholding, Lassosum, LDPred2, GenEpi, PRS-CS, and PRSice2. Furthermore, PGSbuilder provides an intuitive user interface to examine the annotated functional effects of variants from known biomedical databases and relevant literature using advanced natural language processing approaches. In conclusion, PGSbuilder offers a reliable platform to aid researchers in advancing the public perception of genomic risk and precision medicine for human disease genetics. PGSbuilder is freely accessible at http://pgsb.tw23.org.