1,383 research outputs found

    UniCog: A Framework Proposal for the Dynamic Compilation of Comparative Data for the Reconstruction of proto-Ryukyuan

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    国立国語研究所信州大学名桜大学NINJALShinshu UniversityMeio University本稿では,琉球祖語の再建に向けて,琉球諸語の比較データを動的に構築できる枠組みを提案する。UniCog(Unified Cognacy Framework for proto-Ryukyuan)と呼ぶこの枠組みは,琉球諸語に分布する約7,400語の同源語リストを伴っており,その中核には琉球諸語を対象とする既存の全ての語彙データを紐付けるための同源語IDシステムがある。本枠組みを記述した後,具体例を示しながら,この枠組みの実装によって開かれる研究可能性について述べる。最後に,語形の比較を目的とする,琉球諸語の統一的な表記も提案する。この枠組みの導入が日琉諸語の歴史比較言語学の分野においていくらかの貢献を果たすことが期待される。In this paper, we propose a framework which includes an approximately 7,400-word cognate list for the dynamic compilation of comparative data with the goal of reconstructing proto-Ryukyuan. The core concept of this framework, which we call UniCog (Unified Cognacy Framework for proto-Ryukyuan), is to provide a cognate ID system to link all the existing lexicographic data of the Ryukyuan languages. We then show what can actually be achieved with this framework in terms of dynamic compilation of comparative data. Lastly, we propose a standardized orthography for all Ryukyuan dialects for the specific aim of comparing and aligning the word-forms between the doculects. We hope that the introduction of this framework will make some contribution to the field of historical linguistics of Japonic languages.application/pdfdepartmental bulletin pape

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Comparative genomics of recent adaptation in Candida pathogens

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    [eng] Fungal infections pose a serious health threat, affecting >1,000 million people and causing ~1.5 million deaths each year. The problem is growing due to insufficient diagnostic and therapeutic options, increased number of susceptible patients, expansion of pathogens partly linked to climate change and the rise of antifungal drug resistance. Among other fungal pathogens, Candida species are a major cause of severe hospital-acquired infections, with high mortality in immunocompromised patients. Various Candida pathogens constitute a public health issue, which require further efforts to develop new drugs, optimize currently available treatments and improve diagnostics. Given the high dynamism of Candida genomes, a promising strategy to improve current therapies and diagnostics is to understand the evolutionary mechanisms of adaptation to antifungal drugs and to the human host. Previous work using in vitro evolution, population genomics, selection inferences and Genome Wide Association Studies (GWAS) have partially clarified such recent adaptation, but various open questions remain. In the three research articles that conform this PhD thesis we addressed some of these gaps from the perspective of comparative genomics. First, we addressed methodological issues regarding the analysis of Candida genomes. Studying recent adaptation in these pathogens requires adequate bioinformatic tools for variant calling, filtering and functional annotation. Among other reasons, current methods are suboptimal due to limited accuracy to identify structural variants from short read sequencing data. In addition, there is a need for easy-to-use, reproducible variant calling pipelines. To address these gaps we developed the “personalized Structural Variation detection” pipeline (perSVade), a framework to call, filter and annotate several variant types, including structural variants, directly from reads. PerSVade enables accurate identification of structural variants in any species of interest, such as Candida pathogens. In addition, our tool automatically predicts the structural variant calling accuracy on simulated genomes, which informs about the reliability of the calling process. Furthermore, perSVade can be used to analyze single nucleotide polymorphisms and copy number-variants, so that it facilitates multi-variant, reproducible genomic studies. This tool will likely boost variant analyses in Candida pathogens and beyond. Second, we addressed open questions about recent adaptation in Candida, using perSVade for variant identification. On the one hand, we investigated the evolutionary mechanisms of drug resistance in Candida glabrata. For this, we used a large-scale in vitro evolution experiment to study adaptation to two commonly-used antifungals: fluconazole and anidulafungin. Our results show rapid adaptation to one or both drugs, with moderate fitness costs and through few mutations in a narrow set of genes. In addition, we characterize a novel role of ERG3 mutations in cross-resistance towards fluconazole in anidulafungin-adapted strains. These findings illuminate the mutational paths leading to drug resistance and cross-resistance in Candida pathogens. On the other hand, we reanalyzed ~2,000 public genomes and phenotypes to understand the signs of recent selection and drug resistance in six major Candida species: C. auris, C. glabrata, C. albicans, C. tropicalis, C. parapsilosis and C. orthopsilosis. We found hundreds of genes under recent selection, suggesting that clinical adaptation is diverse and complex. These involve species-specific but also convergently affected processes, such as cell adhesion, which could underlie conserved adaptive mechanisms. In addition, using GWAS we predicted known drivers of antifungal resistance alongside potentially novel players. Furthermore, our analyses reveal an important role of generally-overlooked structural variants, and suggest an unexpected involvement of (para)sexual recombination in the spread of resistance. Taken together, our findings provide novel insights on how Candida pathogens adapt to human-related environments and suggest candidate genes that deserve future attention. In summary, the results of this thesis improve our knowledge about the mechanisms of recent adaptation in Candida pathogens, which may enable improved therapeutic and diagnostic applications.[cat] Les infeccions fúngiques representen una greu amenaça per a la salut, afectant a més de 1.000 milions de persones i causant aproximadament 1,5 milions de morts cada any. El problema està augmentant a causa d’unes opcions terapèutiques i diagnòstiques insuficients, l'increment del nombre de pacients susceptibles, l'expansió dels patògens parcialment vinculada al canvi climàtic i l'augment de la resistència als fàrmacs antifúngics. D’entre diversos fongs patògens, els llevats del gènere Candida són una causa important d'infeccions nosocomials, amb una alta mortalitat en pacients immunodeprimits. Diverses espècies de Candida constitueixen un problema de salut pública, cosa que requereix més esforços per a desenvolupar nous medicaments, optimitzar els tractaments disponibles i millorar els diagnòstics. Tenint en compte el dinamisme genòmic d’aquests patògens, una estratègia prometedora per millorar les teràpies i diagnòstics actuals és comprendre els mecanismes evolutius d'adaptació als fàrmacs antifúngics i a l’hoste humà. Treballs anteriors utilitzant l'evolució in vitro, la genòmica de poblacions, les inferències de selecció i els estudis d'associació de genoma complet (GWAS, per les sigles en anglès) han aclarit parcialment aquesta adaptació recent, però encara hi ha diverses preguntes obertes. En els tres articles que conformen aquesta tesi doctoral, hem abordat algunes d'aquestes preguntes des de la perspectiva de la genòmica comparativa. En primer lloc, hem abordat qüestions metodològiques relatives a l'anàlisi dels genomes de les espècies Candida. L'estudi de l'adaptació recent en aquests patògens requereix eines bioinformàtiques adequades per a la detecció, filtratge i anotació funcional de variants genètiques. Entre altres raons, els mètodes actuals són subòptims a causa de la limitada precisió per identificar variants estructurals a partir de dades de seqüenciació amb lectures curtes. A més, hi ha una necessitat d’eines computacionals per a la detecció de variants que siguin senzilles d'utilitzar i reproduibles. Per abordar aquestes mancances, hem desenvolupat el mètode bioinformàtic "personalized Structural Variation detection" (perSVade), una eina que permet la detecció, filtratge i anotació de diversos tipus de variants, incloent-hi les variants estructurals, directament des de les lectures. PerSVade permet la identificació precisa de les variants estructurals en qualsevol espècie d'interès, com ara els patògens Candida. A més, la nostra eina prediu automàticament la precisió de la detecció d’aquestes variants en genomes simulats, la qual cosa informa sobre la fiabilitat del procés. Finalment, perSVade es pot utilitzar per analitzar altres tipus de variants, com els polimorfismes de nucleòtid únic o els canvis en el nombre de còpies, facilitant així estudis genòmics integrals i reproduibles. Aquesta eina probablement impulsarà les anàlisis genòmiques en els patògens Candida i també en altres espècies. En segon lloc, hem abordat algunes de les preguntes obertes sobre l'adaptació recent en els llevats Candida, utilitzant perSVade per a la identificació de variants. D'una banda, hem investigat els mecanismes evolutius de resistència als fàrmacs antifúngics en Candida glabrata. Per a això, hem utilitzat un experiment d'evolució in vitro a gran escala per estudiar l'adaptació a dos antifúngics comuns: el fluconazol i l’anidulafungina. Els nostres resultats mostren una adaptació ràpida a un o ambdós fàrmacs, amb un cost per al creixement moderat i a través de poques mutacions en un nombre reduït de gens. A més, hem caracteritzat un paper nou de les mutacions en ERG3 en la resistència creuada al fluconazol en soques adaptades a anidulafungina. Aquests descobriments aclareixen els processos mutacionals que condueixen a la resistència als fàrmacs i a la resistència creuada en els patògens Candida. D'altra banda, hem re-analitzat aproximadament 2.000 genomes i fenotips disponibles en repositoris públics per a comprendre els senyals genòmics de selecció recent i de resistència a fàrmacs antifúngics, en sis espècies rellevants de Candida: C. auris, C. glabrata, C. albicans, C. tropicalis, C. parapsilosis i C. orthopsilosis. Hem trobat centenars de gens sota selecció recent, suggerint que l'adaptació clínica és diversa i complexa. Aquests gens estan relacionats amb funcions específiques de cada espècie, però també trobem processos alterats de manera similar en diferents patògens, com per exemple l’adhesió cel·lular, cosa que indica fenòmens d’adaptació conservats. A part, utilitzant GWAS hem predit mecanismes esperats de resistència a antifúngics i també possibles nous factors. A més, les nostres anàlisis revelen un paper important de les variants estructurals, generalment poc estudiades, i suggereixen una implicació inesperada de la recombinació (para)sexual en la propagació de la resistència. En conjunt, els nostres descobriments proporcionen noves perspectives sobre com els patògens Candida s'adapten als entorns humans, i suggereixen gens candidats que mereixen investigacions futures. En resum, els resultats d’aquesta tesi milloren el nostre coneixement sobre els mecanismes d'adaptació recent en els patògens Candida, cosa que pot permetre el disseny de noves teràpies i diagnòstics

    A Tale of Two Approaches: Comparing Top-Down and Bottom-Up Strategies for Analyzing and Visualizing High-Dimensional Data

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    The proliferation of high-throughput and sensory technologies in various fields has led to a considerable increase in data volume, complexity, and diversity. Traditional data storage, analysis, and visualization methods are struggling to keep pace with the growth of modern data sets, necessitating innovative approaches to overcome the challenges of managing, analyzing, and visualizing data across various disciplines. One such approach is utilizing novel storage media, such as deoxyribonucleic acid~(DNA), which presents efficient, stable, compact, and energy-saving storage option. Researchers are exploring the potential use of DNA as a storage medium for long-term storage of significant cultural and scientific materials. In addition to novel storage media, scientists are also focussing on developing new techniques that can integrate multiple data modalities and leverage machine learning algorithms to identify complex relationships and patterns in vast data sets. These newly-developed data management and analysis approaches have the potential to unlock previously unknown insights into various phenomena and to facilitate more effective translation of basic research findings to practical and clinical applications. Addressing these challenges necessitates different problem-solving approaches. Researchers are developing novel tools and techniques that require different viewpoints. Top-down and bottom-up approaches are essential techniques that offer valuable perspectives for managing, analyzing, and visualizing complex high-dimensional multi-modal data sets. This cumulative dissertation explores the challenges associated with handling such data and highlights top-down, bottom-up, and integrated approaches that are being developed to manage, analyze, and visualize this data. The work is conceptualized in two parts, each reflecting the two problem-solving approaches and their uses in published studies. The proposed work showcases the importance of understanding both approaches, the steps of reasoning about the problem within them, and their concretization and application in various domains

    Complexity Science in Human Change

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    This reprint encompasses fourteen contributions that offer avenues towards a better understanding of complex systems in human behavior. The phenomena studied here are generally pattern formation processes that originate in social interaction and psychotherapy. Several accounts are also given of the coordination in body movements and in physiological, neuronal and linguistic processes. A common denominator of such pattern formation is that complexity and entropy of the respective systems become reduced spontaneously, which is the hallmark of self-organization. The various methodological approaches of how to model such processes are presented in some detail. Results from the various methods are systematically compared and discussed. Among these approaches are algorithms for the quantification of synchrony by cross-correlational statistics, surrogate control procedures, recurrence mapping and network models.This volume offers an informative and sophisticated resource for scholars of human change, and as well for students at advanced levels, from graduate to post-doctoral. The reprint is multidisciplinary in nature, binding together the fields of medicine, psychology, physics, and neuroscience

    Statistical analysis and modelling of proteomic and genetic network data illuminate hidden roles of proteins and their connections

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    While many stable protein complexes are known, the dynamic interactome is still underexplored. Experimental techniques such as single-tag affinity purification, aim to close the gap and identify transient interactions, but need better filtering tools to discriminate between true interactors and noise. This thesis develops and contrasts two complementary approaches to the analysis of protein-protein interaction (PPI) networks derived from noisy experiments. The majority of data used for the analysis come from in vitro experiments aggregated from known databases (IntAct, BioGRID, BioPlex), but is also complemented by experiments done by our collaborators from the Ueffing group in the Institute of Ophthalmic Research, Tübingen University (Germany). Chapter 3 presents the statistical approach to the data analysis. It focuses on the case of a single dataset with target and control data in order to determine the significant interactions for the target. The procedure follows an expected trajectory of preprocessing, quality control, statistical testing, correction and discussion of results. The approach is tailored to the specific dataset, experiment design and related assumptions. This is specifically relevant for the missing value imputation where multiple approaches are discussed and a new method, building upon a previous method, is proposed and validated. Chapter 4 presents a different approach for the filtering of experimental results for PPIs. It is a statistic, WeSA (weighted socio-affinity), which improves upon previous methods of scoring PPIs from affinity proteomics data. It uses network analysis techniques to analyse the full PPI network without the need for controls. WeSA is tested on protein-protein networks of varying accuracy, including the curated IntAct dataset, the unfiltered records in BioGRID, and the large BioPlex dataset. The model is also tested against the previous same-goal method. While the function itself proves superior, another major advantage is that it can efficiently combine and compare observations across studies and can therefore be used to aggregate and clean results from incoming experiments in the context of all already available data. In the final part, uses of WeSA beyond wild-type PPI networks are analysed. The framework is proposed as a novel way to effectively compare mechanistic differences between variants of the same protein (e.g. mutant vs wild type). I also explore the use of WeSA to study other biological and non-biological networks such as genome-wide association studies (GWAS) and gene-phenotype associations, with encouraging results. In conclusion, this work presents and compares a variety of mathematical, statistical and computational approaches adapted, combined and/or developed specifically for the task of obtaining a better overview of protein-protein interaction networks. The novel methods performance is validated and, specifically, WeSA, is extensively tested and analysed, including beyond the field of PPI networks

    Animals in Dutch travel writing, 1800-present

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    Apart from humans, animals play a pivotal role in travel literature. However, the way they are represented in texts can vary from living companions to metaphorical entities. Existing studies mainly focus on the representation of conventional or unconventional roles that are assigned to animals from around the Napoleonic age until now, roles that have been subject to change and that tell us a lot about human reflections on encounters with non-human creatures and the position of man in this rapidly changing world. In this edited volume, scholars from the Netherlands and abroad analyse the roles that animals play in Dutch travel literature from 1800 to the present. In this way, we aim to provide new insights into the relationships between man and animals, in textual expressions and real life, and to add the ‘Dutch case’ to the flourishing international field of travel writing studies

    ACARORUM CATALOGUS IX. Acariformes, Acaridida, Schizoglyphoidea (Schizoglyphidae), Histiostomatoidea (Histiostomatidae, Guanolichidae), Canestrinioidea (Canestriniidae, Chetochelacaridae, Lophonotacaridae, Heterocoptidae), Hemisarcoptoidea (Chaetodactylidae, Hyadesiidae, Algophagidae, Hemisarcoptidae, Carpoglyphidae, Winterschmidtiidae)

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    The 9th volume of the series Acarorum Catalogus contains lists of mites of 13 families, 225 genera and 1268 species of the superfamilies Schizoglyphoidea, Histiostomatoidea, Canestrinioidea and Hemisarcoptoidea. Most of these mites live on insects or other animals (as parasites, phoretic or commensals), some inhabit rotten plant material, dung or fungi. Mites of the families Chetochelacaridae and Lophonotacaridae are specialised to live with Myriapods (Diplopoda). The peculiar aquatic or intertidal mites of the families Hyadesidae and Algophagidae are also included.Publishe

    How can genomic data inform biological invasions?

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    Rates of biological invasions are increasing, with global trade and climate change causing significant damage to biodiversity, human well-being, primary industries, and economies around the world. However, our ability to predict and prevent future invasions is limited by significant gaps in our mechanistic understanding of the invasion process. Advances in next generation sequencing technologies and bioinformatics make it possible to investigate potential genomic factors that drive invasion success with much higher resolution and accuracy than prior research based on a small number of genetic loci. My thesis argues for the value of population genomic data in invasion biology, first examining the uptake of genomics in invasion research and then providing a case study for using genomic data to understand invasion patterns of pink bollworm (Pectinophora gossypiella). The first analysis (Chapter 2) compares the extent to which population genetic data versus population genomic data, including reference genomes, have been used or are publicly available to study globally invasive species from the International Union for Conservation of Nature (IUCN) “100 of the World’s Worst Invasive Alien Species” (WAS) list. In this chapter, I demonstrate that ‘invasion genomics’ is still in its infancy with respect to research uptake: while 82% of species on the WAS list have been studied using some form of population genetic data, just 32% have been studied using population genomic data. Further, 55% of the WAS list species lack a reference genome, however 18% of these were sequenced in the last three years, indicating a growing investment in genomic resources that looks promising for future invasion genomics research. The second analysis (Chapter 3) showcases population genomic data being used as a tool to inform a biological invasion. Pink bollworm is one of the most destructive global pests of cotton, costing farmers millions of dollars each year in productivity losses and management efforts. A small population of pink bollworm is currently established in North West Australia, where it poses a significant threat to the expanding cotton industry there. In this chapter, I analysed genomic data in the form of single nucleotide polymorphisms (SNPs) – obtained through a reduced representation, genotyping-by- sequencing technique (DArTseq) – for global populations of pink bollworm to elucidate the population structure and connectivity patterns of the pest. My results show that pink bollworm populations in my dataset have low genetic diversity and strong differentiation between populations from different continents. Importantly, the high genetic differentiation between Australia and other continents reduces concerns about gene flow to North West Australia, particularly from populations in India and Pakistan that have evolved resistance to transgenic insecticidal cotton. As species continue to move globally beyond their natural ranges, understanding how genome-driven processes facilitate invasion is critical. Genomic data can enhance our mechanistic understanding of the invasion process and inform proactive management of invasive species. Yet, despite progress in this space, there remain limitations to the breadth and depth of such studies that are highlighted throughout my thesis. These represent valuable research opportunities. With the cost of generating genomic data constantly decreasing and long-read sequencing bridging the gap for many taxon-specific challenges, genomic data is starting to address many previously intractable research questions and has the potential to improve overall biosecurity outcomes worldwide
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