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McAdams, D.

Publications and source records attributed to McAdams, D..

2 recordsLinked to original sources

A near-tight lower bound on the density of forward sampling schemes

MotivationSampling k-mers is a ubiquitous task in sequence analysis algorithms. Sampling schemes such as the often-used random minimizer scheme are particularly appealing as they guarantee at least one k-mer is selected out of every w consecutive k-mers. Sampling fewer k-mers often leads to an increase in efficiency of downstream methods. Thus, developing schemes that have low density, i.e., have a small proportion of sampled k-mers, is an active area of research. After over a decade of consistent efforts in both decreasing the density of practical schemes and increasing the lower bound on the best possible density, there is still a large gap between the two. ResultsWe prove a near-tight lower bound on the density of forward sampling schemes, a class of schemes that generalizes minimizer schemes. For small w and k, we observe that our bound is tight when k {equiv} 1 (mod w). For large w and k, the bound can be approximated by [Formula]. Importantly, our lower bound implies that existing schemes are much closer to achieving optimal density than previously known. For example, with the current default minimap2 HiFi settings w = 19 and k = 19, we show that the best known scheme for these parameters, the double decycling-set-based minimizer of Pellow et al., is at most 3% denser than optimal, compared to the previous gap of at most 50%. Furthermore, when k {equiv} 1 (mod w) and the alphabet size{sigma} goes to {infty}, we show that mod-minimizers introduced by Groot Koerkamp and Pibiri achieve optimal density matching our lower bound. Availability and implementationMinimizer implementations: github.com/RagnarGrootKoerkamp/minimizers ILP and analysis: github.com/treangenlab/sampling-scheme-analysis

bioinformatics↗

Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation

Rapid point-of-care resistance diagnostics (POC-RD) are thought to be a key tool in the fight against antibiotic resistance. By tailoring drug choice to infection genotype, doctors can improve treatment efficacy while limiting costs of inappropriate antibiotic prescription. Here we combine epidemiological theory and data to assess the potential of POC-RD innovations in a public health context, as a means to limit or even reverse selection for antibiotic resistance. POC-RD can be used to impose a non-biological fitness cost on resistant strains, by triggering targeted interventions that reduce their opportunities for transmission. We assess this diagnostic-imposed fitness cost in the context of a spectrum of bacterial population biologies and POC-RD conditional strategies, and find that the expected impact varies from selection against resistance for obligate pathogens to marginal public health improvements for opportunistic pathogens with high bystander antibiotic exposure during asymptomatic carriage (e.g. the pneumococcus). We close by generalizing the notion of RD-informed strategies to incorporate both POC and carriage surveillance information, and illustrate that coupling transmission control interventions to the discovery of resistant strains in carriage can potentially select against resistance in a broad range of opportunistic pathogens.

epidemiology↗