Information reuse in comparative genomics

Heringa, J. [Promotor]Nekrutenko, A. [Copromotor

Speaking through Silence: Communicating Trauma through Metaphorical Imagery in Una\u27s Becoming Unbecoming

Narratives of trauma have become a leading topic in graphic novels because of the power that graphic narratives have to transcend “dominant tropes of unspeakability, invisibility, and inaudibility that have tended to characterize trauma theory” (Hillary Chute Graphic Women 3). Through the medium’s combination of verbal and visual components, cartoonists have the opportunity to more clearly represent inexpressible trauma on the page. Una’s graphic memoir Becoming Unbecoming does just this: uses visual structures to communicate ineffable trauma. Una’s accounts of sexual trauma often remain elusive, largely due to the silence attributed to her intra-diegetic narrator. As a result, the silence of the intra-diegetic Una brings the artistic renderings of her subjective reality into the forefront of her graphic memoir. Her imagery is largely informed by her sexual trauma which visually conveys the emotional distress that cannot be communicated by the young Una. These images, better defined as metaphorical imagery, emerge to fill the gaps of silence between the intra- and extra-diegetic Una in the form of landscapes, bodily distortions, and intertextual allusions – all of which become indicative of her interior landscape and representative of her traumatic experiences. While these images epitomize the intra-diegetic Una’s emotional turmoil and trauma, they also shift at the end of the graphic memoir to frame a survivor’s narrative of liberation

Tracking repeats using significance and transitivty.

transitivity; extreme value distribution Motivation: Internal repeats in coding sequences correspond to structural and functional units of proteins. Moreover, duplication of fragments of coding sequences is known to be a mechanism to facilitate evolution. Identification of repeats is crucial to shed light on the function and structure of proteins, and explain their evolutionary past. The task is difficult because during the course of evolution many repeats diverged beyond recognition. Results: We introduce a new method TRUST, for ab-initio determination of internal repeats in proteins. It provides an improvement in prediction quality as compared to alternative state-of-the-art methods. The increased sensitivity and accuracy of the method is achieved by exploiting the concept of transitivity of alignments. Starting from significant local suboptimal alignments, the application of transitivity allows us to: 1) identify distant repeat homologues for which no alignments were found; 2) gain confidence about consistently well-aligned regions; and 3) recognize and reduce the contribution of nonhomologous repeats. This reassessment step enables us to derive a virtually noise-free profile representing a generalized repeat with high fidelity. We also obtained superior specificity by employing rigid statistical testing for self-sequence and profile-sequence alignments. Assessment was done using a database of repeat annotations based on structural superpositioning. The results show that TRUST is a useful and reliable tool for mining tandem and non-tandem repeats in protein sequence databases, able to predict multiple repeat types with varying intervening segments within a single sequence

Matrix Metalloproteinases, Synaptic Injury, and Multiple Sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system in which immune mediated damage to myelin is characteristic. For an overview of this condition and its pathophysiology, please refer to one of many excellent published reviews (Sorensen and Ransohoff, 1998; Weiner, 2009). To follow, is a discussion focused on the possibility that synaptic injury occurs in at least a subset of patients, and that matrix metalloproteinases (MMPs) play a role in such

Expansion of the human mitochondrial proteome by intra- and inter-compartmental protein duplication

The human mitochondrial proteome is shown to have expanded due to duplication of protein encoding genes and re-localization of these duplicated proteins

Ribosomal DNA, tri- and bi-partite pericentromeres in the permanent translocation heterozygote Rhoeo spathacea

High- and low-stringency FISH and base-specific fluorescence were performed on the permanent translocation heterozygote Rhoeo spathacea (2n = 12). Our results indicate that 45S rDNA arrays, rDNA-related sequences and other GC-rich DNA fraction(s) are located within the pericentromeric regions of all twelve chromosomes, usually colocalizing with the chromomycin A3-positive bands. Homogenization of the pericentromeric regions appears to result from the concerted spread of GC-rich sequences, with differential amplification likely. We found new 5S rDNA patterns, which suggest a variability in the breakpoints and in the consequent chromosome reorganizations. It was found that the large 5S rDNA locus residing on each of the 8E and 9E arms consisted of two smaller loci. On each of the two chromosome arms 3b and 4b, in addition to the major subtelomeric 5S rDNA locus, a new minor locus was found interstitially about 40% along the arm length. The arrangement of cytotogenetic landmarks and chromosome arm measurements are discussed with regard to genome repatterning in Rhoeo

Tree reconciliation combined with subsampling improves large scale inference of orthologous group hierarchies

Background: An orthologous group (OG) comprises a set of orthologous and paralogous genes that share a last common ancestor (LCA). OGs are defined with respect to a chosen taxonomic level, which delimits the position of the LCA in time to a specified speciation event. A hierarchy of OGs expands on this notion, connecting more general OGs, distant in time, to more recent, fine-grained OGs, thereby spanning multiple levels of the tree of life. Large scale inference of OG hierarchies with independently computed taxonomic levels can suffer from inconsistencies between successive levels, such as the position in time of a duplication event. This can be due to confounding genetic signal or algorithmic limitations. Importantly, inconsistencies limit the potential use of OGs for functional annotation and third-party applications. Results: Here we present a new methodology to ensure hierarchical consistency of OGs across taxonomic levels. To resolve an inconsistency, we subsample the protein space of the OG members and perform gene tree-species tree reconciliation for each sampling. Differently from previous approaches, by subsampling the protein space, we avoid the notoriously difficult task of accurately building and reconciling very large phylogenies. We implement the method into a high-throughput pipeline and apply it to the eggNOG database. We use independent protein domain definitions to validate its performance. Conclusion: The presented consistency pipeline shows that, contrary to previous limitations, tree reconciliation can be a useful instrument for the construction of OG hierarchies. The key lies in the combination of sampling smaller trees and aggregating their reconciliations for robustness. Results show comparable or greater performance to previous pipelines. The code is available on Github at: https://github.com/meringlab/og_consistency_pipeline

Complex fate of paralogs

<p>Abstract</p> <p>Background</p> <p>Thanks to recent high coverage mass-spectrometry studies and reconstructed protein complexes, we are now in an unprecedented position to study the evolution of biological systems. Gene duplications, known to be a major source of innovation in evolution, can now be readily examined in the context of protein complexes.</p> <p>Results</p> <p>We observe that paralogs operating in the same complex fulfill different roles: mRNA dosage increase for more than a hundred cytosolic ribosomal proteins, mutually exclusive participation of at least 54 paralogs resulting in alternative forms of complexes, and 24 proteins contributing to <it>bona fide </it>structural growth. Inspection of paralogous proteins participating in two independent complexes shows that an ancient, pre-duplication protein functioned in both multi-protein assemblies and a gene duplication event allowed the respective copies to specialize and split their roles.</p> <p>Conclusion</p> <p>Variants with conditionally assembled, paralogous subunits likely have played a role in yeast's adaptation to anaerobic conditions. In a number of cases the gene duplication has given rise to one duplicate that is no longer part of a protein complex and shows an accelerated rate of evolution. Such genes could provide the raw material for the evolution of new functions.</p

Polki i Polacy na rynku pracy : raport z badań ludności w wieku produkcyjnym realizowanych w 2010 r. w ramach projektu "Bilans Kapitału Ludzkiego"

The study of people of working age is the key research module of the supply side of labour market in BKL Study. Generally, in all the analyses - both those concerning various forms of employment, occupations pursued and positions sought, and those that focus on education and self-evaluation of competences, what comes very much to the forefront is the segmentation of the labour market by the gender of the employers. In the period from August to November 2010 (the duration of the study), more or less one in two people working were employed on the grounds of an employment contract (umowa o pracę), one in nine conducted his own business, one in fourteen had worked during the previous year on the grounds of commission agreement (umowa zlecenia)or contract for a specific task (umowa o dzieło), and one in 20 was working without a formal contract. The differentiation between the genders is already visible at this stage: as far as in the case of regular employment women account for half of all employed people, among those running their own business outside agriculture and also working without contracts, there are on average two men for each woman

Knowledge Graph Completion to Predict Polypharmacy Side Effects

The polypharmacy side effect prediction problem considers cases in which two drugs taken individually do not result in a particular side effect; however, when the two drugs are taken in combination, the side effect manifests. In this work, we demonstrate that multi-relational knowledge graph completion achieves state-of-the-art results on the polypharmacy side effect prediction problem. Empirical results show that our approach is particularly effective when the protein targets of the drugs are well-characterized. In contrast to prior work, our approach provides more interpretable predictions and hypotheses for wet lab validation.Comment: 13th International Conference on Data Integration in the Life Sciences (DILS2018