Polygenic risk scores (PRSs) have been among the leading advances in biomedicine in recent years. As a proxy of genetic liability, PRSs are utilised across multiple fields and applications. While numerous statistical and machine learning methods have been developed to optimise their predictive accuracy, all of these distil genetic liability to a single number based on aggregation of an individual’s genome-wide alleles. This results in a key loss of information about an individual’s genetic profile, which could be critical given the functional sub-structure of the genome and the heterogeneity of complex disease. Here we evaluate the performance of pathway-based PRSs, in which polygenic scores are calculated across genomic pathways for each individual, and we introduce a software, PRSet, for computing and analysing pathway PRSs. We find that pathway PRSs have similar power for evaluating pathway enrichment of GWAS signal as the leading methods, with the distinct advantage of providing estimates of pathway genetic liability at the individual-level. Exemplifying their utility, we demonstrate that pathway PRSs can stratify diseases into subtypes in the UK Biobank with substantially greater power than genome-wide PRSs. Compared to genome-wide PRSs, we expect pathway-based PRSs to offer greater insights into the heterogeneity of complex disease and treatment response, generate more biologically tractable therapeutic targets, and provide a more powerful path to precision medicine.
A series of cases of non-Hodgkin's lymphoma (NHL) were studied by morphology and flow cytometry. The DNA analysis was performed by applying a trypsin digestion method to archival paraffin-embedded samples. DNA aneuploid tumors constituted 47.4% of the total cases, and the frequency in the intermediate and the high malignant grade groups (51.9%, 76.8%) were significantly higher than that of the low grade group (17.6%; P less than 0.05). The S phase fraction (SPF) increased significantly with a high histological malignant grade (P less than 0.005). The mean SPF values of the low, intermediate and high grade lymphomas were 6.5 (0.6-18.8)%, 13.5 (3.2-37.3)% and 23.4 (4.4-41.4)%, respectively. Differences in ploidy status were not associated with survival rate. The survival rate of the cases with high SPF value in all cases of our series and low grade group of NHLs tended to become lower (P = 0.1 and 0.08, respectively). These results suggest that the flow cytometric analysis of DNA content should be a useful means for prediction of prognosis in non-Hodgkin's lymphoma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.