Joint testing of rare variant burden scores using non-negative least squares.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins.

Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank.

Whole-genome sequencing (WGS), whole-exome sequencing (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation and its association with medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield of these approaches when applied to hundreds of thousands of samples to enable the discovery of complex trait genetic signals. Using data for 100 complex traits from 149,195 individuals in the UK Biobank, we systematically compare the relative yield of these strategies in genetic association studies.

A deep catalog of protein-coding variation in 985,830 individuals.

Coding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in the population. Identifying and ascertaining the frequency of such rare variants requires very large sample sizes. Here, we present the largest catalog of human protein-coding variation to date, derived from exome sequencing of 985,830 individuals of diverse ancestry to serve as a rich resource for studying rare coding variants.

Accurate and robust inference of microbial growth dynamics from metagenomic sequencing reveals personalized growth rates.

Patterns of sequencing coverage along a bacterial genome-summarized by a peak-to-trough ratio (PTR)-have been shown to accurately reflect microbial growth rates, revealing a new facet of microbial dynamics and host-microbe interactions. Here, we introduce Compute PTR (CoPTR): a tool for computing PTRs from complete reference genomes and assemblies. Using simulations and data from growth experiments in simple and complex communities, we show that CoPTR is more accurate than the current state of the art while also providing more PTR estimates overall.

Directional Gaussian Mixture Models of the Gut Microbiome Elucidate Microbial Spatial Structure.

The gut microbiome is spatially heterogeneous, with environmental niches contributing to the distribution and composition of microbial populations. A recently developed mapping technology, MaPS-seq, aims to characterize the spatial organization of the gut microbiome by providing data about local microbial populations. However, information about the global arrangement of these populations is lost by MaPS-seq.

An Introduction to Whole-Metagenome Shotgun Sequencing Studies.

Microbial communities are found across diverse environments, including within and across the human body. As many microbes are unculturable in the lab, much of what is known about a microbiome-a collection of bacteria, fungi, archaea, and viruses inhabiting an environment--is from the sequencing of DNA from within the constituent community. Here, we provide an introduction to whole-metagenome shotgun sequencing studies, a ubiquitous approach for characterizing microbial communities, by reviewing three major research areas in metagenomics: assembly, community profiling, and functional profiling.

Efficient and Accurate Inference of Mixed Microbial Population Trajectories from Longitudinal Count Data.

The recently completed second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease, motivating new microbiome study designs based on longitudinal sampling. Yet, analysis of such data is hindered by presence of technical noise, high dimensionality, and data sparsity. Here, we introduce LUMINATE (longitudinal microbiome inference and zero detection), a fast and accurate method for inferring relative abundances from noisy read count data.

Compositional Lotka-Volterra describes microbial dynamics in the simplex.

Dynamic changes in microbial communities play an important role in human health and disease. Specifically, deciphering how microbial species in a community interact with each other and their environment can elucidate mechanisms of disease, a problem typically investigated using tools from community ecology. Yet, such methods require measurements of absolute densities, whereas typical datasets only provide estimates of relative abundances.

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia.

The island of Sardinia has been of particular interest to geneticists for decades. The current model for Sardinia's genetic history describes the island as harboring a founder population that was established largely from the Neolithic peoples of southern Europe and remained isolated from later Bronze Age expansions on the mainland. To evaluate this model, we generate genome-wide ancient DNA data for 70 individuals from 21 Sardinian archaeological sites spanning the Middle Neolithic through the Medieval period.

Intraosseous access in the resuscitation of trauma patients: a literature review.

Purpose: Intraosseous (IO) catheters continue to be recommended in trauma resuscitation. Their utility has recently been debated due to concerns regarding inadequate flow rates during blood transfusion, and the potential for haemolysis. The objective of this review was to examine the evidence for intraosseous catheters in trauma resuscitation, and to highlight areas for future research.

Inference of Population Structure from Time-Series Genotype Data.

Sequencing ancient DNA can offer direct probing of population history. Yet, such data are commonly analyzed with standard tools that assume DNA samples are all contemporary. We present DyStruct, a model and inference algorithm for inferring shared ancestry from temporally sampled genotype data.

FEAST: fast expectation-maximization for microbial source tracking.

A major challenge of analyzing the compositional structure of microbiome data is identifying its potential origins. Here, we introduce fast expectation-maximization microbial source tracking (FEAST), a ready-to-use scalable framework that can simultaneously estimate the contribution of thousands of potential source environments in a timely manner, thereby helping unravel the origins of complex microbial communities ( https://github.com/cozygene/FEAST ).

Survey of Ranavirus and in Introduced Frogs in Hawaii, USA.

Ranaviruses and the fungus are globally important agents of emerging infectious amphibian diseases. Amphibians on Oahu, the Hawaiian Island with the greatest potential for disease introduction through the movement of goods and people, have never been surveyed for ranaviruses or . We surveyed all five species of frogs on Oahu, Hawaii, US for these pathogens.

Form and function: Optional complementizers reduce causal inferences.

Many factors are known to influence the inference of the discourse coherence relationship between two sentences. Here, we examine the relationship between two conjoined embedded clauses in sentences like . In two studies, we find that the presence of before the second embedded clause in such sentences reduces the possibility of a forward causal relationship between the clauses, i.

Accents, Not Just Prosodic Boundaries, Influence Syntactic Attachment.

Traditionally, pitch accents are understood to relate to the information structure of a sentence and its discourse connections, while prosodic boundaries indicate groupings of words and affect how constituents attach into a syntactic structure. Here, we show that accents also affect syntactic attachment in multiple different syntactic structures. Three auditory questionnaires on ambiguous attachment sentences (such as Tom reported that Bill was bribed [last May]) find that accenting the higher or lower verb ( reported or bribed) increases the attachment of the final adverbial phrase as a modifier of the accented verb.

Urbanization shapes the demographic history of a native rodent (the white-footed mouse, Peromyscus leucopus) in New York City.

How urbanization shapes population genomic diversity and evolution of urban wildlife is largely unexplored. We investigated the impact of urbanization on white-footed mice,Peromyscus leucopus,in the New York City (NYC) metropolitan area using coalescent-based simulations to infer demographic history from the site-frequency spectrum. We assigned individuals to evolutionary clusters and then inferred recent divergence times, population size changes and migration using genome-wide single nucleotide polymorphisms genotyped in 23 populations sampled along an urban-to-rural gradient.

Comparative Population Genomics of African Montane Forest Mammals Support Population Persistence across a Climatic Gradient and Quaternary Climatic Cycles.

The Eastern Afromontane biodiversity hotspot (EABH) has the highest concentration of biodiversity in tropical Africa, yet few studies have investigated recent historical diversification processes in EABH lineages. Herein, we analyze restriction-site associated DNA-sequences (RAD-Seq) to study recent historical processes in co-distributed mouse (Hylomyscus) and shrew (Sylvisorex) species complexes, with an aim to better determine how historical paleoenvironmental processes might have contributed to the EABH's high diversity. We analyzed complete SNP matrices of > 50,000 RAD loci to delineate populations, reconstruct the history of isolation and admixture, and discover geographic patterns of genetic partitioning.