Nguyen, N. Q. | bioRxiv Science

bioRxiv2023

Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase [~]50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.

genomics↗

bioRxiv2020

Remodeling of Chemotaxis is a Cornerstone of Bacterial Swarming

Many bacteria use flagella-driven motility to swarm or move collectively over a surface terrain. Bacterial adaptations for swarming can include cell elongation, hyper-flagellation, recruitment of special stator proteins and surfactant secretion, among others. We recently demonstrated another swarming adaptation in Escherichia coli, wherein the chemotaxis pathway is remodeled to increase run durations (decrease tumble bias), with running speeds increased as well. We show here that the modification of motility parameters during swarming is not unique to E. coli, but shared by a diverse group of bacteria we examined - Proteus mirabilis, Serratia marcescens, Salmonella enterica, Bacillus subtilis, and Pseudomonas aeruginosa - suggesting that altering the chemosensory physiology is a cornerstone of swarming. ImportanceBacteria within a swarm move characteristically in packs, displaying an intricate swirling motion where hundreds of dynamic packs continuously form and dissociate as the swarm colonizes increasing expanse of territory. The demonstrated property of E. coli to reduce its tumble bias and hence increase its run duration during swarming is expected to maintain/promote side-by-side alignment and cohesion within the bacterial packs. Here we observe a similar low tumble bias in five different bacterial species, both Gram positive and Gram negative, each inhabiting a unique habitat and posing unique problems to our health. The unanimous display of an altered run-tumble bias in swarms of all species examined here suggests that this behavioral adaptation is crucial for swarming.

microbiology↗