Biology subjects

Anderson, E.

Publications and source records attributed to Anderson, E..

5 recordsLinked to original sources

bioRxiv2018

Evidence that recurrent Group A streptococcus tonsillitis is animmunosusceptibility disease involving antibody deficiency and aberrant Tfh cells

One Sentence SummaryRecurrent tonsillitis is a multifactorial disease associated with an aberrant tonsillar germinal center response to Group A Streptococcus.\n\nABSTRACTRecurrent Group A Streptococcus (GAS) tonsillitis (RT) is a common indication for pediatric tonsillectomy. Strep throat is highly prevalent among children; yet, it is unknown why some children develop RT. To gain insights into this classic childhood disease, we performed phenotypic, genotypic, and functional studies on pediatric GAS RT and non-RT tonsils. We observed significantly smaller germinal centers in GAS RT tonsils, and underrepresentation of GAS-specific germinal center follicular helper (GC Tfh) CD4+ T cells. RT children exhibited reduced antibody responses to GAS virulence factor SpeA. Risk and protective HLA Class II alleles for RT were identified. Finally, SpeA induced granzyme B+ GC Tfh cells in RT tonsils that had capacity to kill B cells. Together, these observations suggest that RT susceptibility can occur due to genetic differences that can result in aberrant GC Tfh cells and poor antibody responses to GAS SpeA.

immunology↗

bioRxiv2018

Single tube bead-based DNA co-barcoding for cost effective and accurate sequencing, haplotyping, and assembly

Obtaining accurate sequences from long DNA molecules is very important for genome assembly and other applications. Here we describe single tube long fragment read (stLFR), a technology that enables this a low cost. It is based on adding the same barcode sequence to sub-fragments of the original long DNA molecule (DNA co-barcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process up to 3.6 billion unique barcode sequences were generated on beads, enabling practically non-redundant co-barcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique co-barcoding of over 8 million 20-300 kb genomic DNA fragments. Analysis of the genome of the human genome NA12878 with stLFR demonstrated high quality variant calling and phasing into contigs up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries and their construction did not significantly add to the time or cost of whole genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.

genomics↗

bioRxiv2017

The causal effect of educational attainment on Alzheimer’s disease: A two-sample Mendelian randomization study

BackgroundObservational evidence suggests that higher educational attainment is protective for Alzheimers disease (AD). It is unclear whether this association is causal or confounded by demographic and socioeconomic characteristics. We examined the causal effect of educational attainment on AD in a two-sample MR framework.\n\nMethodsWe extracted all available effect estimates of the 74 single nucleotide polymorphisms (SNPs) associated with years of schooling from the largest genome-wide association study (GWAS) of educational attainment (N=293,723) and the GWAS of AD conducted by the International Genomics of Alzheimers Project (n=17,008 AD cases and 37,154 controls). SNP-exposure and SNP-outcome coefficients were combined using an inverse variance weighted approach, providing an estimate of the causal effect of each SD increase in years of schooling on AD. We also performed appropriate sensitivity analyses examining the robustness of causal effect estimates to the various assumptions and conducted simulation analyses to examine potential survival bias of MR analyses.\n\nFindingsWith each SD increase in years of schooling (3.51 years), the odds of AD were, on average, reduced by approximately one third (odds ratio= 0.63, 95% confidence interval [CI]: 0.48 to 0.83, p<0.001). Causal effect estimates were consistent when using causal methods with varying MR assumptions or different sets of SNPs for educational attainment, lending confidence to the magnitude and direction of effect in our main findings. There was also no evidence of survival bias in our study.\n\nInterpretationOur findings support a causal role of educational attainment on AD, whereby an additional [~]3.5 years of schooling reduces the odds of AD by approximately one third.

epidemiology↗

bioRxiv2017

Evaluating Clinical Stop-Smoking Services Globally: Proposal For A Minimum Data Set

Background and aimsBehavioural and pharmacological support for smoking cessation improves the chances of success and represents a highly cost-effective way of preventing chronic disease and premature death. There are a large number of clinical stop-smoking services around the world. These could be connected into a global network to provide data to assess what treatment components are most effective, for what populations, in what settings. This requires data to be collected according to a minimum standard set of data items. This paper sets out a proposal for this global minimum data set.\n\nMethodsWe reviewed sets of data items used in clinical services that have already benefited from standardised approaches to using data. We identified client and treatment data items that may directly or indirectly influence outcome, and outcome variables that were practicable to obtain in clinical practice. We then consulted service providers in countries that may have an interest in taking part in a global network of smoking cessation services, and revised the sets of data items according to their feedback.\n\nResultsThree sets of data items are proposed. The first is a set of features characterising treatments offered by a service. The second is a core set of data items describing clients characteristics, engagement with the service, and outcomes. The third is an extended set of client data items to be captured in addition to the core data items wherever resources permit.\n\nConclusionsWe propose minimum standards for capturing data from clinical smoking cessation services globally. This could provide a basis for meaningful evaluations of different smoking cessation treatments in different populations in a variety of settings across many countries.

epidemiology↗

bioRxiv2016

Identifying Migrant Origins Using Genetics, Isotopes, and Habitat Suitability

O_LIIdentifying migratory connections across the annual cycle is important for studies of migrant ecology, evolution, and conservation. While recent studies have demonstrated the utility of high-resolution SNP-based genetic markers for identifying population-specific migratory patterns, the accuracy of this approach relative to other intrinsic tagging techniques has not yet been assessed.\nC_LIO_LIHere, using a straightforward application of Bayes' Rule, we develop a method for combining inferences from high-resolution genetic markers, stable isotopes, and habitat suitability models, to spatially infer the breeding origin of migrants captured anywhere along their migratory pathway. Using leave-one-out cross validation, we compare the accuracy of this combined approach with the accuracy attained using each source of data independently.\nC_LIO_LIOur results indicate that when each method is considered in isolation, the accuracy of genetic assignments far exceeded that of assignments based on stable isotopes or habitat suitability models. However, our joint assignment method consistently resulted in small, but informative increases in accuracy and did help to correct misassignments based on genetic data alone. We demonstrate the utility of the combined method by identifying previously undetectable patterns in the timing of migration in a North American migratory songbird, the Wilson's warbler.\nC_LIO_LIOverall, our results support the idea that while genetic data provides the most accurate method for tracking animals using intrinsic markers when each method is considered independently, there is value in combining all three methods. The resulting methods are provided as part of a new computationally-efficient R-package, GIAIH, allowing broad application of our statistical framework to other migratory animal systems.\nC_LI

ecology↗