Selectoscope: A Modern Web-App for Positive Selection Analysis of Genomic Data

Selectoscope is a web application which combines a number of popular tools used to infer positive selection in an easy to use pipeline. A set of homologous DNA sequences to be analyzed and evaluated are submitted to the server by uploading protein-coding gene sequences in the FASTA format. The sequences are aligned and a phylogenetic tree is constructed. The codeml procedure from the PAML package is used first to adjust branch lengths and to find a starting point for the likelihood maximization, then FastCodeML is executed. Upon completion, branches and positions under positive selection are visualized simultaneously on the tree and alignment viewers. Run logs are accessible through the web interface. Selectoscope is based on the Docker virtualization technology. This makes the application easy to install with a negligible performance overhead. The application is highly scalable and can be used on a single PC or on a large high performance clusters. The source code is freely available at https://github.com/anzaika/selectoscope

State aggregation for fast likelihood computations in molecular evolution.

MOTIVATION: Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models. RESULTS: We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analysed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics. AVAILABILITY: The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml). CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans.

Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier "significant" genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution

The Higgs field and the ultraviolet behaviour of the vortex operator in 2+1 dimensions

We calculate the change in the ultraviolet behaviour of the vortex operator due to the presence of dynamical Higgs field in both 2+1 dimensional QED and the 2+1 dimensional Georgi-Glashow model. We find that in the QED case the presence of the Higgs field leads at the one loop level to power like correction to the propagator of the vortex operator. On the other hand, in the Georgi-Glashow model, the adjoint Higgs at one loop has no affect on the vortex propagator. Thus, as long as the mass of the Higgs field is much larger than the gauge coupling constant, the ultraviolet behaviour of the vortex operator in the Georgi-Glashow model is independent of the Higgs mass.Comment: 14 page

Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp.

The genus Burkholderia consists of species that occupy remarkably diverse ecological niches. Its best known members are important pathogens, B. mallei and B. pseudomallei, which cause glanders and melioidosis, respectively. Burkholderia genomes are unusual due to their multichromosomal organization, generally comprised of 2-3 chromosomes. We performed integrated genomic analysis of 127 Burkholderia strains. The pan-genome is open with the saturation to be reached between 86,000 and 88,000 genes. The reconstructed rearrangements indicate a strong avoidance of intra-replichore inversions that is likely caused by selection against the transfer of large groups of genes between the leading and the lagging strands. Translocated genes also tend to retain their position in the leading or the lagging strand, and this selection is stronger for large syntenies. Integrated reconstruction of chromosome rearrangements in the context of strains phylogeny reveals parallel rearrangements that may indicate inversion-based phase variation and integration of new genomic islands. In particular, we detected parallel inversions in the second chromosomes of B. pseudomallei with breakpoints formed by genes encoding membrane components of multidrug resistance complex, that may be linked to a phase variation mechanism. Two genomic islands, spreading horizontally between chromosomes, were detected in the B. cepacia group. This study demonstrates the power of integrated analysis of pan-genomes, chromosome rearrangements, and selection regimes. Non-random inversion patterns indicate selective pressure, inversions are particularly frequent in a recent pathogen B. mallei, and, together with periods of positive selection at other branches, may indicate adaptation to new niches. One such adaptation could be a possible phase variation mechanism in B. pseudomallei

Large-Scale Comparative Analysis of Codon Models Accounting for Protein and Nucleotide Selection.

There are numerous sources of variation in the rate of synonymous substitutions inside genes, such as direct selection on the nucleotide sequence, or mutation rate variation. Yet scans for positive selection rely on codon models which incorporate an assumption of effectively neutral synonymous substitution rate, constant between sites of each gene. Here we perform a large-scale comparison of approaches which incorporate codon substitution rate variation and propose our own simple yet effective modification of existing models. We find strong effects of substitution rate variation on positive selection inference. More than 70% of the genes detected by the classical branch-site model are presumably false positives caused by the incorrect assumption of uniform synonymous substitution rate. We propose a new model which is strongly favored by the data while remaining computationally tractable. With the new model we can capture signatures of nucleotide level selection acting on translation initiation and on splicing sites within the coding region. Finally, we show that rate variation is highest in the highly recombining regions, and we propose that recombination and mutation rate variation, such as high CpG mutation rate, are the two main sources of nucleotide rate variation. Although we detect fewer genes under positive selection in Drosophila than without rate variation, the genes which we detect contain a stronger signal of adaptation of dynein, which could be associated with Wolbachia infection. We provide software to perform positive selection analysis using the new model

Light outputs of yttrium doped BaF_2 crystals irradiated with neutrons

Abstract The fast luminescence component of barium fluoride (BaF_2) crystals with a subnanosecond decay time can find wide application in particle physics and nuclear physics. However, the slow luminescence component with the 630 ns decay time could cause pile-up signals at a high rate environment. Doping of BaF2 crystals with rare earth elements suppresses the slow emission component, but at the same time the radiation hardness of the crystals deteriorates. This work presents the results of studying crystal samples, both pure BaF2 and those doped with yttrium in a proportion of 1 at.%Y, 3 at.%Y and 5 at.%Y, irradiated with a fast neutron fluence of about 2.3×1014 n/cm2. Their light output and decay kinetics were measured before and after irradiation. It is found that the light output loss of a pure BaF2 crystal after irradiation is about 7%, and the light output loss of yttrium doped samples after irradiation is about two times higher. The measurement results demonstrate that after irradiation the fast component of each sample has a relative light output loss 2–3% larger than the slow one.</jats:p