Removing reference bias and improving indel calling in ancient DNA data analysis by mapping to a sequence variation graph

Abstract: Background: During the last decade, the analysis of ancient DNA (aDNA) sequence has become a powerful tool for the study of past human populations. However, the degraded nature of aDNA means that aDNA molecules are short and frequently mutated by post-mortem chemical modifications. These features decrease read mapping accuracy and increase reference bias, in which reads containing non-reference alleles are less likely to be mapped than those containing reference alleles. Alternative approaches have been developed to replace the linear reference with a variation graph which includes known alternative variants at each genetic locus. Here, we evaluate the use of variation graph software vg to avoid reference bias for aDNA and compare with existing methods. Results: We use vg to align simulated and real aDNA samples to a variation graph containing 1000 Genome Project variants and compare with the same data aligned with bwa to the human linear reference genome. Using vg leads to a balanced allelic representation at polymorphic sites, effectively removing reference bias, and more sensitive variant detection in comparison with bwa, especially for insertions and deletions (indels). Alternative approaches that use relaxed bwa parameter settings or filter bwa alignments can also reduce bias but can have lower sensitivity than vg, particularly for indels. Conclusions: Our findings demonstrate that aligning aDNA sequences to variation graphs effectively mitigates the impact of reference bias when analyzing aDNA, while retaining mapping sensitivity and allowing detection of variation, in particular indel variation, that was previously missed

Flory-Huggins theory for athermal mixtures of hard spheres and larger flexible polymers

A simple analytic theory for mixtures of hard spheres and larger polymers with excluded volume interactions is developed. The mixture is shown to exhibit extensive immiscibility. For large polymers with strong excluded volume interactions, the density of monomers at the critical point for demixing decreases as one over the square root of the length of the polymer, while the density of spheres tends to a constant. This is very different to the behaviour of mixtures of hard spheres and ideal polymers, these mixtures although even less miscible than those with polymers with excluded volume interactions, have a much higher polymer density at the critical point of demixing. The theory applies to the complete range of mixtures of spheres with flexible polymers, from those with strong excluded volume interactions to ideal polymers.Comment: 9 pages, 4 figure

Ecological Speciation Promoted by Divergent Regulation of Functional Genes Within African Cichlid Fishes

Rapid ecological speciation along depth gradients has taken place repeatedly in freshwater fishes, yet molecular mechanisms facilitating such diversification are typically unclear. In Lake Masoko, an African crater lake, the cichlid Astatotilapia calliptera has diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants, and examine their contributions to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 5.4% were regulated by cis-regulatory expression QTLs, and 9.2% were regulated by cis-regulatory splicing QTLs. We also found strong signals of divergent selection on differentially expressed genes associated with craniofacial development. These results suggest that large-scale transcriptome modification plays an important role during early-stage speciation. We conclude that regulatory-variants are important targets of selection driving ecologically-relevant divergence in gene expression during adaptive diversification

Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation

Many aspects of high-temperature gauge theories, such as the electroweak baryon number violation rate, color conductivity, and the hard gluon damping rate, have previously been understood only at leading logarithmic order (that is, neglecting effects suppressed only by an inverse logarithm of the gauge coupling). We discuss how to systematically go beyond leading logarithmic order in the analysis of physical quantities. Specifically, we extend to next-to-leading-log order (NLLO) the simple leading-log effective theory due to Bodeker that describes non-perturbative color physics in hot non-Abelian plasmas. A suitable scaling analysis is used to show that no new operators enter the effective theory at next-to-leading-log order. However, a NLLO calculation of the color conductivity is required, and we report the resulting value. Our NLLO result for the color conductivity can be trivially combined with previous numerical work by G. Moore to yield a NLLO result for the hot electroweak baryon number violation rate.Comment: 20 pages, 1 figur

Pfam: clans, web tools and services

Pfam is a database of protein families that currently contains 7973 entries (release 18.0). A recent development in Pfam has enabled the grouping of related families into clans. Pfam clans are described in detail, together with the new associated web pages. Improvements to the range of Pfam web tools and the first set of Pfam web services that allow programmatic access to the database and associated tools are also presented. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://pfam.cgb.ki.se/)

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.Fil: Krubiner, Carleigh B.. University Johns Hopkins; Estados UnidosFil: Faden, Ruth R.. University Johns Hopkins; Estados UnidosFil: Karron, Ruth A.. University Johns Hopkins; Estados UnidosFil: Little, Margaret O.. University Of Georgetown; Estados UnidosFil: Lyerly, Anne D.. University of North Carolina; Estados UnidosFil: Abramson, Jon S.. University Wake Forest; Estados UnidosFil: Beigi, Richard H.. Magee-Womens Hospital of University of Pittsburgh Medical Center; Estados UnidosFil: Cravioto, Alejandro R.. Universidad Nacional Autónoma de México; MéxicoFil: Durbin, Anna P.. University Johns Hopkins; Estados UnidosFil: Gellin, Bruce G.. Sabin Vaccine Institute; Estados UnidosFil: Gupta, Swati B.. IAVI; Estados UnidosFil: Kaslow, David C.. PATH; Estados UnidosFil: Kochhar, Sonali. Global Healthcare Consulting; IndiaFil: Luna, Florencia. Facultad Latinoamericana de Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saenz, Carla. Pan American Health Organization; Estados UnidosFil: Sheffield, Jeanne S.. University Johns Hopkins; Estados UnidosFil: Tindana, Paulina O.. Navrongo Health Research Centre; GhanaFil: The Prevent Working Group. No especifíca