Echinobase: a resource to support the echinoderm research community.

Echinobase (www.echinobase.org) is a model organism knowledgebase serving as a resource for the community that studies echinoderms, a phylum of marine invertebrates that includes sea urchins and sea stars. Echinoderms have been important experimental models for over 100 years and continue to make important contributions to environmental, evolutionary, and developmental studies, including research on developmental gene regulatory networks. As a centralized resource, Echinobase hosts genomes and collects functional genomic data, reagents, literature, and other information for the community. This third-generation site is based on the Xenbase knowledgebase design and utilizes gene-centric pages to minimize the time and effort required to access genomic information. Summary gene pages display gene symbols and names, functional data, links to the JBrowse genome browser, and orthology to other organisms and reagents, and tabs from the Summary gene page contain more detailed information concerning mRNAs, proteins, diseases, and protein-protein interactions. The gene pages also display 1:1 orthologs between the fully supported species Strongylocentrotus purpuratus (purple sea urchin), Lytechinus variegatus (green sea urchin), Patiria miniata (bat star), and Acanthaster planci (crown-of-thorns sea star). JBrowse tracks are available for visualization of functional genomic data from both fully supported species and the partially supported species Anneissia japonica (feather star), Asterias rubens (sugar star), and L. pictus (painted sea urchin). Echinobase serves a vital role by providing researchers with annotated genomes including orthology, functional genomic data aligned to the genomes, and curated reagents and data. The Echinoderm Anatomical Ontology provides a framework for standardizing developmental data across the phylum, and knowledgebase content is formatted to be findable, accessible, interoperable, and reusable by the research community.

Xenbase: key features and resources of the Xenopus model organism knowledgebase.

Xenbase (https://www.xenbase.org/), the Xenopus model organism knowledgebase, is a web-accessible resource that integrates the diverse genomic and biological data from research on the laboratory frogs Xenopus laevis and Xenopus tropicalis. The goal of Xenbase is to accelerate discovery and empower Xenopus research, to enhance the impact of Xenopus research data, and to facilitate the dissemination of these data. Xenbase also enhances the value of Xenopus data through high-quality curation, data integration, providing bioinformatics tools optimized for Xenopus experiments, and linking Xenopus data to human data, and other model organisms. Xenbase also plays an indispensable role in making Xenopus data interoperable and accessible to the broader biomedical community in accordance with FAIR principles. Xenbase provides annotated data updates to organizations such as NCBI, UniProtKB, Ensembl, the Gene Ontology consortium, and most recently, the Alliance of Genomic Resources, a common clearing house for data from humans and model organisms. This article provides a brief overview of key and recently added features of Xenbase. New features include processing of Xenopus high-throughput sequencing data from the NCBI Gene Expression Omnibus; curation of anatomical, physiological, and expression phenotypes with the newly created Xenopus Phenotype Ontology; Xenopus Gene Ontology annotations; new anatomical drawings of the Normal Table of Xenopus development; and integration of the latest Xenopus laevis v10.1 genome annotations. Finally, we highlight areas for future development at Xenbase as we continue to support the Xenopus research community.

The Xenopus phenotype ontology: bridging model organism phenotype data to human health and development.

BACKGROUND: Ontologies of precisely defined, controlled vocabularies are essential to curate the results of biological experiments such that the data are machine searchable, can be computationally analyzed, and are interoperable across the biomedical research continuum. There is also an increasing need for methods to interrelate phenotypic data easily and accurately from experiments in animal models with human development and disease. RESULTS: Here we present the Xenopus phenotype ontology (XPO) to annotate phenotypic data from experiments in Xenopus, one of the major vertebrate model organisms used to study gene function in development and disease. The XPO implements design patterns from the Unified Phenotype Ontology (uPheno), and the principles outlined by the Open Biological and Biomedical Ontologies (OBO Foundry) to maximize interoperability with other species and facilitate ongoing ontology management. Constructed in Web Ontology Language (OWL) the XPO combines the existing uPheno library of ontology design patterns with additional terms from the Xenopus Anatomy Ontology (XAO), the Phenotype and Trait Ontology (PATO) and the Gene Ontology (GO). The integration of these different ontologies into the XPO enables rich phenotypic curation, whilst the uPheno bridging axioms allows phenotypic data from Xenopus experiments to be related to phenotype data from other model organisms and human disease. Moreover, the simple post-composed uPheno design patterns facilitate ongoing XPO development as the generation of new terms and classes of terms can be substantially automated. CONCLUSIONS: The XPO serves as an example of current best practices to help overcome many of the inherent challenges in harmonizing phenotype data between different species. The XPO currently consists of approximately 22,000 terms and is being used to curate phenotypes by Xenbase, the Xenopus Model Organism Knowledgebase, forming a standardized corpus of genotype-phenotype data that can be directly related to other uPheno compliant resources.

Sheared granular matter and the empirical relations of seismicity.

The frictional instability associated with earthquake initiation and earthquake dynamics is believed to be mainly controlled by the dynamics of fragmented rocks within the fault gauge. Principal features of the emerging seismicity (e.g., intermittent dynamics and broad time and/or energy scales) have been replicated by simple experimental setups, which involve a slowly driven slider on top of granular matter, for example. Yet these setups are often physically limited and might not allow one to determine the underlying nature of specific features and, hence, the universality and generality of the experimental observations. Here, we address this challenge by a numerical study of a spring-slider experiment based on two-dimensional discrete element method simulations, which allows us to control the properties of the granular matter and of the surface of the slider, for example. Upon quasistatic loading, stick-slip-type behavior emerges which is contrasted by a stable sliding regime at finite driving rates, in agreement with experimental observations. Across large parameter ranges for damping, interparticle friction, particle polydispersity, etc., the earthquake-like dynamics associated with the former regime results in several robust scale-free statistical features also observed in experiments. At first sight, these closely resemble the main empirical relations of tectonic seismicity at geological scales. This includes the Gutenberg-Richter distribution of event sizes, the Omori-Utsu-type decay of aftershock rates, as well as the aftershock productivity relation and broad recurrence time distributions. Yet, we show that the correlations associated with tectonic aftershocks are absent such that the origin of the Omori-Utsu relation, the aftershock productivity relation, and Båth's relation in the simulations is fundamentally different from the case of tectonic seismicity. This, we believe, is mainly due to a lack of macroscale relaxation processes that are closely tied to the generation of real aftershocks. We argue that the same is true for previous laboratory experiments.

Echinobase: leveraging an extant model organism database to build a knowledgebase supporting research on the genomics and biology of echinoderms.

Echinobase (www.echinobase.org) is a third generation web resource supporting genomic research on echinoderms. The new version was built by cloning the mature Xenopus model organism knowledgebase, Xenbase, refactoring data ingestion pipelines and modifying the user interface to adapt to multispecies echinoderm content. This approach leveraged over 15 years of previous database and web application development to generate a new fully featured informatics resource in a single year. In addition to the software stack, Echinobase uses the private cloud and physical hosts that support Xenbase. Echinobase currently supports six echinoderm species, focused on those used for genomics, developmental biology and gene regulatory network analyses. Over 38 000 gene pages, 18 000 publications, new improved genome assemblies, JBrowse genome browser and BLAST + services are available and supported by the development of a new echinoderm anatomical ontology, uniformly applied formal gene nomenclature, and consistent orthology predictions. A novel feature of Echinobase is integrating support for multiple, disparate species. New genomes from the diverse echinoderm phylum will be added and supported as data becomes available. The common code development design of the integrated knowledgebases ensures parallel improvements as each resource evolves. This approach is widely applicable for developing new model organism informatics resources.

Materials Informatics for Mechanical Deformation: A Review of Applications and Challenges.

In the design and development of novel materials that have excellent mechanical properties, classification and regression methods have been diversely used across mechanical deformation simulations or experiments. The use of materials informatics methods on large data that originate in experiments or/and multiscale modeling simulations may accelerate materials' discovery or develop new understanding of materials' behavior. In this fast-growing field, we focus on reviewing advances at the intersection of data science with mechanical deformation simulations and experiments, with a particular focus on studies of metals and alloys. We discuss examples of applications, as well as identify challenges and prospects.

Classifying domain-specific text documents containing ambiguous keywords.

A keyword-based search of comprehensive databases such as PubMed may return irrelevant papers, especially if the keywords are used in multiple fields of study. In such cases, domain experts (curators) need to verify the results and remove the irrelevant articles. Automating this filtering process will save time, but it has to be done well enough to ensure few relevant papers are rejected and few irrelevant papers are accepted. A good solution would be fast, work with the limited amount of data freely available (full paper body may be missing), handle ambiguous keywords and be as domain-neutral as possible. In this paper, we evaluate a number of classification algorithms for identifying a domain-specific set of papers about echinoderm species and show that the resulting tool satisfies most of the abovementioned requirements. Echinoderms consist of a number of very different organisms, including brittle stars, sea stars (starfish), sea urchins and sea cucumbers. While their taxonomic identifiers are specific, the common names are used in many other contexts, creating ambiguity and making a keyword search prone to error. We try classifiers using Linear, Naïve Bayes, Nearest Neighbor, Tree, SVM, Bagging, AdaBoost and Neural Network learning models and compare their performance. We show how effective the resulting classifiers are in filtering irrelevant articles returned from PubMed. The methodology used is more dependent on the good selection of training data and is a practical solution that can be applied to other fields of study facing similar challenges. Database URL: The code and date reported in this paper are freely available at http://xenbaseturbofrog.org/pub/Text-Topic-Classifier/.

Integration of 1:1 orthology maps and updated datasets into Echinobase.

Echinobase (https://echinobase.org) is a central online platform that generates, manages and hosts genomic data relevant to echinoderm research. While the resource primarily serves the echinoderm research community, the recent release of an excellent quality genome for the frequently studied purple sea urchin (Strongylocentrotus purpuratus genome, v5.0) has provided an opportunity to adapt to the needs of a broader research community across other model systems. To this end, establishing pipelines to identify orthologous genes between echinoderms and other species has become a priority in many contexts including nomenclature, linking to data in other model organisms, and in internal functionality where data gathered in one hosted species can be associated with genes in other hosted echinoderms. This paper describes the orthology pipelines currently employed by Echinobase and how orthology data are processed to yield 1:1 ortholog mappings between a variety of echinoderms and other model taxa. We also describe functions of interest that have recently been included on the resource, including an updated developmental time course for S.purpuratus, and additional tracks for genome browsing. These data enhancements will increase the accessibility of the resource to non-echinoderm researchers and simultaneously expand the data quality and quantity available to core Echinobase users. Database URL: https://echinobase.org.

Xenbase: deep integration of GEO & SRA RNA-seq and ChIP-seq data in a model organism database.

Xenbase (www.xenbase.org) is a knowledge base for researchers and biomedical scientists that employ the amphibian Xenopus as a model organism in biomedical research to gain a deeper understanding of developmental and disease processes. Through expert curation and automated data provisioning from various sources Xenbase strives to integrate the body of knowledge on Xenopus genomics and biology together with the visualization of biologically significant interactions. Most current studies utilize next generation sequencing (NGS) but until now the results of different experiments were difficult to compare and not integrated with other Xenbase content. Xenbase has developed a suite of tools, interfaces and data processing pipelines that transforms NCBI Gene Expression Omnibus (GEO) NGS content into deeply integrated gene expression and chromatin data, mapping all aligned reads to the most recent genome builds. This content can be queried and visualized via multiple tools and also provides the basis for future automated 'gene expression as a phenotype' and gene regulatory network analyses.

From plastic flow to brittle fracture: Role of microscopic friction in amorphous solids.

Plasticity in soft amorphous materials typically involves collective deformation patterns that emerge on intense shearing. The microscopic basis of amorphous plasticity has been commonly established through the notion of "Eshelby"-type events, localized abrupt rearrangements that induce flow in the surrounding material via nonlocal elastic-type interactions. This universal mechanism in flowing disordered solids has been proposed despite their diversity in terms of scales, microscopic constituents, or interactions. Using a numerical particle-based study, we argue that the presence of frictional interactions in granular solids alters the dynamics of flow by nucleating micro shear cracks that continually coalesce to build up system-spanning fracturelike formations on approach to failure. The plastic-to-brittle failure transition is controlled by the degree of frictional resistance which is in essence similar to the role of heterogeneities that separate the abrupt and smooth yielding regimes in glassy structures.

Seasonal temperature, the lunar cycle and diurnal rhythms interact in a combinatorial manner to modulate genomic responses to the environment in a reef-building coral.

Rhythms of various periodicities drive cyclical processes in organisms ranging from single cells to the largest mammals on earth, and on scales from cellular physiology to global migrations. The molecular mechanisms that generate circadian behaviours in model organisms have been well studied, but longer phase cycles and interactions between cycles with different periodicities remain poorly understood. Broadcast spawning corals are one of the best examples of an organism integrating inputs from multiple environmental parameters, including seasonal temperature, the lunar phase and hour of the day, to calibrate their annual reproductive event. We present a deep RNA-sequencing experiment utilizing multiple analyses to differentiate transcriptomic responses modulated by the interactions between the three aforementioned environmental parameters. Acropora millepora was sampled over multiple 24-hr periods throughout a full lunar month and at two seasonal temperatures. Temperature, lunar and diurnal cycles produce distinct transcriptomic responses, with interactions between all three variables identifying a core set of genes. These core genes include mef2, a developmental master regulator, and two heterogeneous nuclear ribonucleoproteins, one of which is known to post-transcriptionally interact with mef2 and with biological clock-regulating mRNAs. Interactions between diurnal and temperature differences impacted a range of core processes ranging from biological clocks to stress responses. Genes involved with developmental processes and transcriptional regulation were impacted by the lunar phase and seasonal temperature differences. Lastly, there was a diurnal and lunar phase interaction in which genes involved with RNA-processing and translational regulation were differentially regulated. These data illustrate the extraordinary levels of transcriptional variation across time in a simple radial cnidarian in response to the environment under normal conditions.

Xenbase: Facilitating the Use of Xenopus to Model Human Disease.

At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man and all vertebrate species. Leveraging this conservation, researchers are increasingly using the experimental advantages of the amphibian Xenopus to model human disease. The online Xenopus resource, Xenbase, enables human disease modeling by curating the Xenopus literature published in PubMed and integrating these Xenopus data with orthologous human genes, anatomy, and more recently with links to the Online Mendelian Inheritance in Man resource (OMIM) and the Human Disease Ontology (DO). Here we review how Xenbase supports disease modeling and report on a meta-analysis of the published Xenopus research providing an overview of the different types of diseases being modeled in Xenopus and the variety of experimental approaches being used. Text mining of over 50,000 Xenopus research articles imported into Xenbase from PubMed identified approximately 1,000 putative disease- modeling articles. These articles were manually assessed and annotated with disease ontologies, which were then used to classify papers based on disease type. We found that Xenopus is being used to study a diverse array of disease with three main experimental approaches: cell-free egg extracts to study fundamental aspects of cellular and molecular biology, oocytes to study ion transport and channel physiology and embryo experiments focused on congenital diseases. We integrated these data into Xenbase Disease Pages to allow easy navigation to disease information on external databases. Results of this analysis will equip Xenopus researchers with a suite of experimental approaches available to model or dissect a pathological process. Ideally clinicians and basic researchers will use this information to foster collaborations necessary to interrogate the development and treatment of human diseases.

Self-diffusion in plastic flow of amorphous solids.

We report on a particle-based numerical study of sheared amorphous solids in the dense slow flow regime. In this framework, deformation and flow are accompanied by critical fluctuation patterns associated with the macroscopic plastic response. The former is commonly attributed to the collective slip patterns that relax internal stresses within the bulk material and give rise to an effective mechanical noise governing the latter particle-level process. In this paper, the avalanche-type dynamics between plastic events is shown to have a strong relevance on the self-diffusion of tracer particles in the Fickian regime. As a consequence, strong size effects emerge in the effective diffusion coefficient that is rationalized in terms of avalanche size distributions and the relevant temporal occurrence.

Distinguishing Species Using GC Contents in Mixed DNA or RNA Sequences.

With the advent of whole transcriptome and genome analysis methods, classifying samples containing multiple origins has become a significant task. Nucleotide sequences can be allocated to a genome or transcriptome by aligning sequences to multiple target sequence sets, but this approach requires extensive computational resources and also depends on target sequence sets lacking contaminants, which is often not the case. Here, we demonstrate that raw sequences can be rapidly sorted into groups, in practice corresponding to genera, by exploiting differences in nucleotide GC content. To do so, we introduce GCSpeciesSorter, which uses classification, specifically Support Vector Machines (SVM) and the C4.5 decision tree generator, to differentiate sequences. It also implements a secondary BLAST feature to identify known outliers. In the test case presented, a hermatypic coral holobiont, the cnidarian host includes various endosymbionts. The best characterized and most common of these symbionts are zooxanthellae of the genus Symbiodinium. GCSpeciesSorter separates cnidarian from Symbiodinium sequences with a high degree of accuracy. We show that if the GC contents of the species differ enough, this method can be used to accurately distinguish the sequences of different species when using high-throughput sequencing technologies.

Navigating Xenbase: An Integrated Xenopus Genomics and Gene Expression Database.

Xenbase is the Xenopus model organism database ( www.xenbase.org ), a web-accessible resource that integrates the diverse genomic and biological data for Xenopus research. It hosts a variety of content including current and archived genomes for both X. laevis and X. tropicalis, bioinformatic tools for comparative genetic analyses including BLAST and GBrowse, annotated Xenopus literature, and catalogs of reagents including antibodies, ORFeome clones, morpholinos, and transgenic lines. Xenbase compiles gene-specific pages which include manually curated gene expression images, functional information including gene ontology (GO), disease associations, and links to other major data sources such as NCBI:Entrez, UniProtKB, and Ensembl. We also maintain the Xenopus Anatomy Ontology (XAO) which describes anatomy throughout embryonic development. This chapter provides a full description of the many features of Xenbase, and offers a guide on how to use various tools to perform a variety of common tasks such as identifying nucleic acid or protein sequences, finding gene expression patterns for specific genes, stages or tissues, identifying literature on a specific gene or tissue, locating useful reagents and downloading our extensive content, including Xenopus gene-Human gene disease mapping files.

Correlation and shear bands in a plastically deformed granular medium.

Recent experiments (Le Bouil et al., Phys. Rev. Lett., 2014, 112, 246001) have analyzed the statistics of local deformation in a granular solid undergoing plastic deformation. Experiments report strongly anisotropic correlation between events, with a characteristic angle that was interpreted using elasticity theory and the concept of Eshelby transformations with dilation; interestingly, the shear bands that characterize macroscopic failure occur at an angle that is different from the one observed in microscopic correlations. Here, we interpret this behavior using a mesoscale elastoplastic model of solid flow that incorporates a local Mohr-Coulomb failure criterion. This differs from the interpretation of Le Bouil et al., which is based on purely elastic considerations ignoring the potential role of local friction on deformation patterns. We show that the angle observed in the microscopic correlations can be understood by combining the elastic interactions associated with Eshelby transformation with the local failure criterion. At large strains, we also induce permanent shear bands at an angle that is different from the one observed in the correlation pattern. We interpret this angle as the one that leads to the maximal instability of slip lines.

Xenbase: a genomic, epigenomic and transcriptomic model organism database.

Xenbase (www.xenbase.org) is an online resource for researchers utilizing Xenopus laevis and Xenopus tropicalis, and for biomedical scientists seeking access to data generated with these model systems. Content is aggregated from a variety of external resources and also generated by in-house curation of scientific literature and bioinformatic analyses. Over the past two years many new types of content have been added along with new tools and functionalities to reflect the impact of high-throughput sequencing. These include new genomes for both supported species (each with chromosome scale assemblies), new genome annotations, genome segmentation, dynamic and interactive visualization for RNA-Seq data, updated ChIP-Seq mapping, GO terms, protein interaction data, ORFeome support, and improved connectivity to other biomedical and bioinformatic resources.

Inertia and universality of avalanche statistics: The case of slowly deformed amorphous solids.

By means of a finite elements technique we solve numerically the dynamics of an amorphous solid under deformation in the quasistatic driving limit. We study the noise statistics of the stress-strain signal in the steady-state plastic flow, focusing on systems with low internal dissipation. We analyze the distributions of avalanche sizes and durations and the density of shear transformations when varying the damping strength. In contrast to avalanches in the overdamped case, dominated by the yielding point universal exponents, inertial avalanches are controlled by a nonuniversal damping-dependent feedback mechanism, eventually turning negligible the role of correlations. Still, some general properties of avalanches persist and new scaling relations can be proposed.

Anomalous stress fluctuations in athermal two-dimensional amorphous solids.

We numerically study the local stress distribution within athermal, isotropically stressed, mechanically stable, packings of bidisperse frictionless disks above the jamming transition in two dimensions. Considering the Fourier transform of the local stress, we find evidence for algebraically increasing fluctuations in both isotropic and anisotropic components of the stress tensor at small wave numbers, contrary to recent theoretical predictions. Such increasing fluctuations imply a lack of self-averaging of the stress on large length scales. The crossover to these increasing fluctuations defines a length scale ℓ_{0}, however, it appears that ℓ_{0} does not vary much with packing fraction ϕ, nor does ℓ_{0} seem to be diverging as ϕ approaches the jamming ϕ_{J}. We also find similar large length scale fluctuations of stress in the inherent states of a quenched Lennard-Jones liquid, leading us to speculate that such fluctuations may be a general property of amorphous solids in two dimensions.

Role of inertia in the rheology of amorphous systems: A finite-element-based elastoplastic model.

A simple finite-element analysis with varying damping strength is used to model the athermal shear rheology of densely packed glassy systems at a continuum level. We focus on the influence of dissipation on bulk rheological properties. Our numerical studies, done over a wide range of damping coefficients, identify two well-separated rheological regimes along with a crossover region controlled by a critical damping. In the overdamped limit, inertial effects are negligible and the rheological response is well described by the commonly observed Herschel-Bulkley equation. In stark contrast, inertial vibrations in the underdamped regime prompt a significant drop in the mean-stress level, leading to a nonmonotonic constitutive relation. The observed negative slope in the flow curve, which is a signature of mechanical instability and thus permanent shear banding, arises from the sole influence of inertia, in qualitative agreement with the recent molecular dynamics study of Nicolas et al., Phys. Rev. Lett. 116, 058303 (2016).