Moderator Of 2 Sessions
Workshop 02: Tools for Genomic Data Analysis and Visualisation
Target audience: Public health professionals, clinicians and researchers
Please note: All ISPPD-12 Workshops are highly interactive and designed to allow at least 25% active learning for the maximum registrants anticipated.
Presenter Of 1 Presentation
O037 - BACTERIAL MUTATIONS ASSOCIATED WITH MENINGITIS AMONG INVASIVE PNEUMOCOCCAL DISEASE PATIENTS, USA, 2016-2019 (ID 252)
Previous studies have identified several pneumococcal gene mutations that disproportionally affect meningitis patients. Here we aim to confirm previously reported associations and identify additional genes linked to meningitis.
Non-synonymous mutations in previously reported candidate genes, including pbp1B, pspC, zmpB, and pde1, were determined by whole genome sequencing. The association between a candidate mutation and syndrome (meningitis vs. non-meningitis) was evaluated using a linear mixed-effects model (LMM), implemented in the FaST-LMM software, to control for population structure. All k-mers of length 15 were identified from draft genome assemblies. The k-mers present in >5% but <95% of isolates, representing common variants, were evaluated for association with meningitis using LMM.
Of the 11,015 invasive pneumococcal isolates identified in 2016-2019, 763 (7%) were cultured from meningitis patients. Compared to non-meningitis isolates, meningitis isolates had a higher proportion of pbp1B641C (21% vs. 10%), pspC1360A (34% vs. 31%), and zmpB638A (5% vs. 2%) variants. After controlling for population structure, each of the three variants was significantly associated with meningitis (p<0.05). LMM analysis on 2,083,856 k-mers estimated a heritability (h2) of 0.08. K-mers that showed genome-wide significant association (p<1×10-8) with meningitis were identified in genes encoding ABC transporter ATP-binding protein (H020_RS0107080), AraC family transcriptional regulator (H020_RS0107070), and bacteriocin-associated integral membrane family protein (H020_RS0100550), among others.
The pneumococcal genome explained a modest amount of variation in clinical manifestations (meningitis vs. non-meningitis), although a larger proportion of such variation could be due to host and host-pathogen interactions. Further depiction of underlying mechanisms could help better understand bacterial pathogenesis.