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In electroreceptive jawed vertebrates, embryonic lateral line placodes give rise to electrosensory ampullary organs as well as mechanosensory neuromasts. Previous reports of shared gene expression suggest that conserved mechanisms underlie electroreceptor and mechanosensory hair cell development and that electroreceptors evolved as a transcriptionally related “sister cell type” to hair cells. We previously identified only one transcription factor gene, Neurod4, as ampullary organ-restricted in the developing lateral line system of a chondrostean ray-finned fish, the Mississippi paddlefish (Polyodon spathula). The other 16 transcription factor genes we previously validated in paddlefish were expressed in both ampullary organs and neuromasts. Here, we used our published lateral line organ-enriched gene-set (arising from differential bulk RNA-seq in late-larval paddlefish), together with a candidate gene approach, to identify 25 transcription factor genes expressed in the developing lateral line system of a more experimentally tractable chondrostean, the sterlet (Acipenser ruthenus, a small sturgeon), and/or that of paddlefish. Thirteen are expressed in both ampullary organs and neuromasts, consistent with conservation of molecular mechanisms. Seven are electrosensory-restricted on the head (Irx5, Irx3, Insm1, Sp5, Satb2, Mafa and Rorc), and five are the first-reported mechanosensory-restricted transcription factor genes (Foxg1, Sox8, Isl1, Hmx2 and Rorb). However, as previously reported, Sox8 is expressed in ampullary organs as well as neuromasts in a catshark (Scyliorhinus canicula), suggesting the existence of lineage-specific differences between cartilaginous and ray-finned fishes. Overall, our results support the hypothesis that ampullary organs and neuromasts develop via largely conserved transcriptional mechanisms, and identify multiple transcription factors potentially involved in the formation of electrosensory versus mechanosensory lateral line organs.

Abstract The number of databases as well as their size and complexity is increasing. This creates a barrier to use especially for non-experts, who have to come to grips with the nature of the data, the way it has been represented in the database, and the specific query languages or user interfaces by which data are accessed. These difficulties worsen in research settings, where it is common to work with many different databases. One approach to improving this situation is to allow users to pose their queries in natural language. In this work we describe a machine learning framework, Polyglotter, that in a general way supports the mapping of natural language searches to database queries. Importantly, it does not require the creation of manually annotated data for training and therefore can be applied easily to multiple domains. The framework is polyglot in the sense that it supports multiple different database engines that are accessed with a variety of query languages, including SQL and Cypher. Furthermore Polyglotter supports multi-class queries. Good performance is achieved on both toy and real databases, as well as a human-annotated WikiSQL query set. Thus Polyglotter may help database maintainers make their resources more accessible.

Abstract Background Correlation matrices are important in inferring relationships and networks between regulatory or signalling elements in biological systems. With currently available technology sample sizes for experiments are typically small, meaning that these correlations can be difficult to estimate. At a genome-wide scale estimation of correlation matrices can also be computationally demanding. Results We develop an empirical Bayes approach to improve covariance estimates for gene expression, where we assume the covariance matrix takes a block diagonal form. Our method shows lower false discovery rates than existing methods on simulated data. Applied to a real data set from Bacillus subtilis we demonstrate it’s ability to detecting known regulatory units and interactions between them. Conclusions We demonstrate that, compared to existing methods, our method is able to find significant covariances and also to control false discovery rates, even when the sample size is small (n=10). The method can be used to find potential regulatory networks, and it may also be used as a pre-processing step for methods that calculate, for example, partial correlations, so enabling the inference of the causal and hierarchical structure of the networks.

InterMine is a data integration and analysis software system that has been used to create both inter-connected and stand-alone biological databases for the analysis of large and complex biological data sets. Together, the InterMine databases provide access to extensive data across multiple organisms. To provide more convenient access to these data from Android mobile devices, we have developed the InterMine app, an application that can be run on any Android mobile phone or tablet. The InterMine app provides a single interface for data access, search and exploration of the InterMine databases. It can be used to retrieve information on genes and gene lists, and their relatives across species. Simple searches can be used to access a range of data about a specific gene, while links to the InterMine databases provide access to more detailed report pages and gene list analysis tools. The InterMine app thus facilitates rapid exploration of genes across multiple organisms and kinds of data.

[This corrects the article DOI: 10.1371/journal.pone.0106035.].

Bdelloid rotifers are a class of microscopic invertebrates that have existed for millions of years apparently without sex or meiosis. They inhabit a variety of temporary and permanent freshwater habitats globally, and many species are remarkably tolerant of desiccation. Bdelloids offer an opportunity to better understand the evolution of sex and recombination, but previous work has emphasised desiccation as the cause of several unusual genomic features in this group. Here, we present high-quality whole-genome sequences of 3 bdelloid species: Rotaria macrura and R. magnacalcarata, which are both desiccation intolerant, and Adineta ricciae, which is desiccation tolerant. In combination with the published assembly of A. vaga, which is also desiccation tolerant, we apply a comparative genomics approach to evaluate the potential effects of desiccation tolerance and asexuality on genome evolution in bdelloids. We find that ancestral tetraploidy is conserved among all 4 bdelloid species, but homologous divergence in obligately aquatic Rotaria genomes is unexpectedly low. This finding is contrary to current models regarding the role of desiccation in shaping bdelloid genomes. In addition, we find that homologous regions in A. ricciae are largely collinear and do not form palindromic repeats as observed in the published A. vaga assembly. Consequently, several features interpreted as genomic evidence for long-term ameiotic evolution are not general to all bdelloid species, even within the same genus. Finally, we substantiate previous findings of high levels of horizontally transferred nonmetazoan genes in both desiccating and nondesiccating bdelloid species and show that this unusual feature is not shared by other animal phyla, even those with desiccation-tolerant representatives. These comparisons call into question the proposed role of desiccation in mediating horizontal genetic transfer.

The synthetic biology design process has traditionally been heavily dependent upon manual searching, acquisition and integration of existing biological data. A large amount of such data is already available from Internet-based resources, but data exchange between these resources is often undertaken manually. Automating the communication between different resources can be done by the generation of computational workflows to achieve complex tasks that cannot be carried out easily or efficiently by a single resource. Computational workflows involve the passage of data from one resource, or process, to another in a distributed computing environment. In a typical bioinformatics workflow, the predefined order in which processes are invoked in a synchronous fashion and are described in a workflow definition document. However, in synthetic biology the diversity of resources and manufacturing tasks required favour a more flexible model for process execution. Here, the authors present the Protocol for Linking External Nodes (POLEN), a Cloud-based system that facilitates synthetic biology design workflows that operate asynchronously. Messages are used to notify POLEN resources of events in real time, and to log historical events such as the availability of new data, enabling networks of cooperation. POLEN can be used to coordinate the integration of different synthetic biology resources, to ensure consistency of information across distributed repositories through added support for data standards, and ultimately to facilitate the synthetic biology life cycle for designing and implementing biological systems.

The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula). Validation of a subset reveals expression in developing ampullary organs of transcription factor genes critical for hair cell development, and genes essential for glutamate release at hair cell ribbon synapses, suggesting close developmental, physiological and evolutionary links between non-teleost electroreceptors and hair cells. We identify an ampullary organ-specific proneural transcription factor, and candidates for the voltage-sensing L-type Cav channel and rectifying Kv channel predicted from skate (cartilaginous fish) ampullary organ electrophysiology. Overall, our results illuminate ampullary organ development, physiology and evolution.

Summary: The DAGViewer BioJS component is a reusable JavaScript component made available as part of the BioJS project and intended to be used to display graphs of structured data, with a particular emphasis on Directed Acyclic Graphs (DAGs). It enables users to embed representations of graphs of data, such as ontologies or phylogenetic trees, in hyper-text documents (HTML). This component is generic, since it is capable (given the appropriate configuration) of displaying any kind of data that is organised as a graph. The features of this component which are useful for examining and filtering large and complex graphs are described. Availability: http://github.com/alexkalderimis/dag-viewer-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8303.

The construction and analysis of networks is increasingly widespread in biological research. We have developed esyN ("easy networks") as a free and open source tool to facilitate the exchange of biological network models between researchers. esyN acts as a searchable database of user-created networks from any field. We have developed a simple companion web tool that enables users to view and edit networks using data from publicly available databases. Both normal interaction networks (graphs) and Petri nets can be created. In addition to its basic tools, esyN contains a number of logical templates that can be used to create models more easily. The ability to use previously published models as building blocks makes esyN a powerful tool for the construction of models and network graphs. Users are able to save their own projects online and share them either publicly or with a list of collaborators. The latter can be given the ability to edit the network themselves, allowing online collaboration on network construction. esyN is designed to facilitate unrestricted exchange of this increasingly important type of biological information. Ultimately, the aim of esyN is to bring the advantages of Open Source software development to the construction of biological networks.

Coral reefs are major contributors to marine biodiversity. However, they are in rapid decline due to global environmental changes such as rising sea surface temperatures, ocean acidification, and pollution. Genomic and transcriptomic analyses have broadened our understanding of coral biology, but a study of the microRNA (miRNA) repertoire of corals is missing. miRNAs constitute a class of small non-coding RNAs of ∼22 nt in size that play crucial roles in development, metabolism, and stress response in plants and animals alike. In this study, we examined the coral Stylophora pistillata for the presence of miRNAs and the corresponding core protein machinery required for their processing and function. Based on small RNA sequencing, we present evidence for 31 bona fide microRNAs, 5 of which (miR-100, miR-2022, miR-2023, miR-2030, and miR-2036) are conserved in other metazoans. Homologues of Argonaute, Piwi, Dicer, Drosha, Pasha, and HEN1 were identified in the transcriptome of S. pistillata based on strong sequence conservation with known RNAi proteins, with additional support derived from phylogenetic trees. Examination of putative miRNA gene targets indicates potential roles in development, metabolism, immunity, and biomineralisation for several of the microRNAs. Here, we present first evidence of a functional RNAi machinery and five conserved miRNAs in S. pistillata, implying that miRNAs play a role in organismal biology of scleractinian corals. Analysis of predicted miRNA target genes in S. pistillata suggests potential roles of miRNAs in symbiosis and coral calcification. Given the importance of miRNAs in regulating gene expression in other metazoans, further expression analyses of small non-coding RNAs in transcriptional studies of corals should be informative about miRNA-affected processes and pathways.

Bdelloid rotifers are microinvertebrates with unique characteristics: they have survived tens of millions of years without sexual reproduction; they withstand extreme desiccation by undergoing anhydrobiosis; and they tolerate very high levels of ionizing radiation. Recent evidence suggests that subtelomeric regions of the bdelloid genome contain sequences originating from other organisms by horizontal gene transfer (HGT), of which some are known to be transcribed. However, the extent to which foreign gene expression plays a role in bdelloid physiology is unknown. We address this in the first large scale analysis of the transcriptome of the bdelloid Adineta ricciae: cDNA libraries from hydrated and desiccated bdelloids were subjected to massively parallel sequencing and assembled transcripts compared against the UniProtKB database by blastx to identify their putative products. Of ~29,000 matched transcripts, ~10% were inferred from blastx matches to be horizontally acquired, mainly from eubacteria but also from fungi, protists, and algae. After allowing for possible sources of error, the rate of HGT is at least 8%-9%, a level significantly higher than other invertebrates. We verified their foreign nature by phylogenetic analysis and by demonstrating linkage of foreign genes with metazoan genes in the bdelloid genome. Approximately 80% of horizontally acquired genes expressed in bdelloids code for enzymes, and these represent 39% of enzymes in identified pathways. Many enzymes encoded by foreign genes enhance biochemistry in bdelloids compared to other metazoans, for example, by potentiating toxin degradation or generation of antioxidants and key metabolites. They also supplement, and occasionally potentially replace, existing metazoan functions. Bdelloid rotifers therefore express horizontally acquired genes on a scale unprecedented in animals, and foreign genes make a profound contribution to their metabolism. This represents a potential mechanism for ancient asexuals to adapt rapidly to changing environments and thereby persist over long evolutionary time periods in the absence of sex.

Publishing databases in the Resource Description Framework (RDF) model is becoming widely accepted to maximize the syntactic and semantic interoperability of open data in life sciences. Here we report advancements made in the 6th and 7th annual BioHackathons which were held in Tokyo and Miyagi respectively. This review consists of two major sections covering: 1) improvement and utilization of RDF data in various domains of the life sciences and 2) meta-data about these RDF data, the resources that store them, and the service quality of SPARQL Protocol and RDF Query Language (SPARQL) endpoints. The first section describes how we developed RDF data, ontologies and tools in genomics, proteomics, metabolomics, glycomics and by literature text mining. The second section describes how we defined descriptions of datasets, the provenance of data, and quality assessment of services and service discovery. By enhancing the harmonization of these two layers of machine-readable data and knowledge, we improve the way community wide resources are developed and published. Moreover, we outline best practices for the future, and prepare ourselves for an exciting and unanticipatable variety of real world applications in coming years.

InterMine is a data integration and analysis software system that has been used to create both inter-connected and stand-alone biological databases for the analysis of large and complex biological data sets. Together, the InterMine databases provide access to extensive data across multiple organisms. To provide more convenient access to these data from Android mobile devices, we have developed the InterMine app, an application that can be run on any Android mobile phone or tablet. The InterMine app provides a single interface for data access, search and exploration of the InterMine databases. It can be used to retrieve information on genes and gene lists, and their relatives across species. Simple searches can be used to access a range of data about a specific gene, while links to the InterMine databases provide access to more detailed report pages and gene list analysis tools. The InterMine app thus facilitates rapid exploration of genes across multiple organisms and kinds of data.

Summary: The DAGViewer BioJS component is a reusable JavaScript component made available as part of the BioJS project and intended to be used to display graphs of structured data, with a particular emphasis on Directed Acyclic Graphs (DAGs). It enables users to embed representations of graphs of data, such as ontologies or phylogenetic trees, in hyper-text documents (HTML). This component is generic, since it is capable (given the appropriate configuration) of displaying any kind of data that is organised as a graph. The features of this component which are useful for examining and filtering large and complex graphs are described. Availability: http://github.com/alexkalderimis/dag-viewer-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8303.

Summary: The InterMineTable component is a reusable JavaScript component as part of the BioJS project. It enables users to embed powerful table-based query facilities in their websites with access to genomic data-warehouses such as http://www.flymine.org, which allow users to perform flexible queries over a wide range of integrated data types. Availability: http://github.com/alexkalderimis/im-tables-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8301.

Summary: The InterMineTable component is a reusable JavaScript component as part of the BioJS project. It enables users to embed powerful table-based query facilities in their websites with access to genomic data-warehouses such as http://www.flymine.org, which allow users to perform flexible queries over a wide range of integrated data types. Availability: http://github.com/alexkalderimis/im-tables-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8301.