Proteomics stands as the crucial link between genomics and human diseases. Quantitative proteomics provides detailed insights into protein levels, enabling differentiation between distinct phenotypes. OLINK, a biotechnology company from Uppsala, Sweden, offers a targeted, affinity-based protein measurement method called Target 96, which has become prominent in the field of proteomics. The SCALLOP consortium, for instance, contains data from over 70.000 individuals across 45 independent cohort studies, all sampled by OLINK. However, when independent cohorts want to collaborate and quantitatively compare their target 96 protein values, it is currently advised to include 'identical biological bridging' samples in each sampling run to perform a reference sample normalization, correcting technical variations across measurements. Such a 'biological bridging sample' approach requires each of the involved cohorts to resend their biological bridging samples to OLINK to run them all together, which is logistically challenging, costly and time-consuming. Hence alternatives are searched and an evaluation of the current state of the art exposes the need for a more robust method that allows all OLINK Target 96 studies to compare proteomics data accurately and cost-efficiently. To meet these goals we developed the Synthetic Plasma Pool Cohort Correction, the 'SPOC correction' approach, based on the use of an OLINK-composed synthetic plasma sample. The method can easily be implemented in a federated data-sharing context which is illustrated on a sepsis use case.

This paper is a call to action for research and discussion on data visualization education. As visualization evolves and spreads through our professional and personal lives, we need to understand how to support and empower a broad and diverse community of learners in visualization. Data Visualization is a diverse and dynamic discipline that combines knowledge from different fields, is tailored to suit diverse audiences and contexts, and frequently incorporates tacit knowledge. This complex nature leads to a series of interrelated challenges for data visualization education. Driven by a lack of consolidated knowledge, overview, and orientation for visualization education, the 21 authors of this paper-educators and researchers in data visualization-identify and describe 19 challenges informed by our collective practical experience. We organize these challenges around seven themes People, Goals & Assessment, Environment, Motivation, Methods, Materials, and Change. Across these themes, we formulate 43 research questions to address these challenges. As part of our call to action, we then conclude with 5 cross-cutting opportunities and respective action items: embrace DIVERSITY+INCLUSION, build COMMUNITIES, conduct RESEARCH, act AGILE, and relish RESPONSIBILITY. We aim to inspire researchers, educators and learners to drive visualization education forward and discuss why, how, who and where we educate, as we learn to use visualization to address challenges across many scales and many domains in a rapidly changing world: viseducationchallenges.github.io.

The connections in a graph generate a structure that is independent of a coordinate system. This visual metaphor allows creating a more flexible representation of data than a two-dimensional scatterplot. In this article, we present STAD (Simplified Topological Abstraction of Data), a parameter-free dimensionality reduction method that projects high-dimensional data into a graph. STAD generates an abstract representation of high-dimensional data by giving each data point a location in a graph which preserves the approximate distances in the original high-dimensional space. The STAD graph is built upon the Minimum Spanning Tree (MST) to which new edges are added until the correlation between the distances from the graph and the original dataset is maximized. Additionally, STAD supports the inclusion of additional functions to focus the exploration and allow the analysis of data from new perspectives, emphasizing traits in data which otherwise would remain hidden. We demonstrate the effectiveness of our method by applying it to two real-world datasets: traffic density in Barcelona and temporal measurements of air quality in Castile and León in Spain.

SUMMARY: Inferring a Gene Regulatory Network (GRN) from gene expression data is a computationally expensive task, exacerbated by increasing data sizes due to advances in high-throughput gene profiling technology, such as single-cell RNA-seq. To equip researchers with a toolset to infer GRNs from large expression datasets, we propose GRNBoost2 and the Arboreto framework. GRNBoost2 is an efficient algorithm for regulatory network inference using gradient boosting, based on the GENIE3 architecture. Arboreto is a computational framework that scales up GRN inference algorithms complying with this architecture. Arboreto includes both GRNBoost2 and an improved implementation of GENIE3, as a user-friendly open source Python package. AVAILABILITY AND IMPLEMENTATION: Arboreto is available under the 3-Clause BSD license at http://arboreto.readthedocs.io. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High-throughput and high-resolution experimental methods in biology pose enormous challenges for current biological data visualization approaches. To address these challenges, researchers in the visualization and bioinformatics communities need to engage in the design, implementation, application, and evaluation of novel visualization techniques and tools that provide insight into large and highly complex data sets. BioVis 2015 - the fifth Symposium on Biological Data Visualization - brought together researchers from the visualization, bioinformatics, and biology communities to establish an interdisciplinary dialogue and promote the sharing of expertise between both meeting participants and the communities at large. The meeting educated, inspired, and engaged visualization researchers in problems in biological data visualization as well as bioinformatics and biology researchers in state-of-the-art visualization research. The symposium serves as a platform for researchers from these fields to increase the impact of data visualization approaches in biology. The BioVis 2015 symposium is affiliated with ISMB, the Intelligent Systems for Molecular Biology conference, as a Special Interest Group (SIG) and was colocated with ISMB in Dublin, Ireland, July 10-11 2015. Each paper was reviewed by researchers from both the bioinformatics and visualization fields and was evaluated for improvements over state-of-the-art and for scientific soundness. The review process was organized in two review cycles. In the first review cycle, each paper was reviewed by three to four reviewers. In the second review cycle, the primary reviewers checked whether the required revisions for conditionally accepted papers were successfully included. Based on the reviewers' scores, reviews, and recommendations, the BioVis 2015 Paper and Publication Chairs and the BMC Bioinformatics Section Editor together selected those that would be published as a BMC Bioinformatics supplement. The papers from BioVis 2015 appear in two different proceedings: As of the 5th Symposium on Biological Data Visualization: Part 1 in this BMC Bioinformatics supplement and as of the 5th Symposium on Biological Data Visualization: Part 2 in BMC Proceedings (http://www.biomedcentral.com/bmcproc/supplements/9/S6). From the 21 papers submitted to BioVis 2015, 9 papers are published in this BMC Bioinformatics supplement and 5 papers are published in BMC Proceedings. The articles in this supplement cover a wide spectrum of challenging problems in biological data visualization and their solutions. Overall, three main themes arise from the BioVis 2015 articles: omics, proteins, and imaging. In the omics field, Younesy et al. [1] describe VisRseq: a user-friendly interface for biologists to use libraries in R that provides a method for linking R-apps with interactive components. Chelaru et al. [2] expand on the design behind Epiviz, another tool for bringing genome visualization and computational environments together. Hennig et al. [3] describe Pan-Tetris and Aurisano et al. [4] describe BactoGeNIE: both systems are designed for comparing different genomes. The XCluSim tool by L'Yi et al. [5] has a more general application field and aims to provide insight into how different clustering results relate to each other. In the protein field, Stolte et al. [6] give an overview of the design decisions that underlie Aquaria, a visual analytics tool for exploring protein-related data. Finally, three papers are included from the imaging field. Topics range from image generation, as discussed by Abdellah et al. [7], to a method for parameter optimization in image processing by Pretorius et al. [9] (e.g. for cell nuclei detection and colour deconvolution for histology), and all the way to graph-based exploration of histology images in the GRAPHIE system proposed by Ding et al. [8]. The diversity of topics covered in this issue highlights the wide range of challenges in applying existing visualization techniques to biological data. With this analysis and formalization of our collective experiences, we hope to motivate visualization researchers to think about new problems and new approaches to pressing problems in biology.

Recent developments in the field of-omics technologies brought great potential for conducting biomedical research in very efficient manner, but also raised a plethora of new computational challenges to be addressed. Extremely high dimensionality accompanied with poor signal-to-noise ratio and small sample size of data resulting from high-throughput experiments pose previously unprecedented problem, creating an increasing demand for innovative analytical strategies. In this work we propose an island model-based genetic algorithm for multivariate feature selection in the context of-omics data, which accommodates to a particular classification scenario via dynamic tuning of its parameters. We demonstrate it on two publicly available data sets containing gene expression profiles corresponding to the two distinct biomedical questions. We show that the algorithm consistently outperforms two additional feature selection schemes across data sets, regardless to which method is used in the subsequent classification step.

Abstract Summary: Pipit is a gene-centric interactive visualization tool designed to study structural genomic variations. Through focusing on individual genes as the functional unit, researchers are able to study and generate hypotheses on the biological impact of different structural variations, for instance, the deletion of dosage-sensitive genes or the formation of fusion genes. Pipit is a cross-platform Java application that visualizes structural variation data from Genome Variation Format files. Availability: Executables, source code, sample data, documentation and screencast are available at https://bitbucket.org/biovizleuven/pipit. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

SUMMARY: TrioVis is a visual analytics tool developed for filtering on coverage and variant frequency for genomic variants from exome sequencing of parent-child trios. In TrioVis, the variant data are organized by grouping each variant based on the laws of Mendelian inheritance. Taking three Variant Call Format files as input, TrioVis allows the user to test different coverage thresholds (i.e. different levels of stringency), to find the optimal threshold values tailored to their hypotheses and to gain insights into the global effects of filtering through interaction. AVAILABILITY: Executables, source code and sample data are available at https://bitbucket.org/biovizleuven/triovis. Screencast is available at http://vimeo.com/user6757771/triovis. CONTACT: [email protected].

In this paper, we introduce a visualization tool for interactive and efficient exploration of high dimensional data using parallel coordinates. An algorithm is developed to find an optimal permutation of dimensions, which allows the data miner to immediately see the most important features or irregularities in the dataset. This is implemented as a genetic algorithm based on the travelling salesman problem using maximal correlation as fitness. Other features of the tool include selection operators to group the data such as selection by intersection or by angle, orthogonal and density plots complementing the parallel coordinates plot, manual arrangement of permutation order of the dimensions, possibility to show all plots necessary to see all dimensional relations and displaying a certain number of standard deviations for each dimension separately. The tool is applied to multiple gene prioritization cases in search of genes that are relevant to certain genetic disorders. The used datasets are obtained with the MerKator and Endeavour tools and include a Breast cancer, Cataract, Charcoth-Marie-Tooth and Cardiomyopathy dataset, as well as a dataset relating 29 diseases with 22206 genes. Our tool, manual and data can be downloaded from http://www.toomas.be/parcoord/.

SUMMARY: Biogem provides a software development environment for the Ruby programming language, which encourages community-based software development for bioinformatics while lowering the barrier to entry and encouraging best practices. Biogem, with its targeted modular and decentralized approach, software generator, tools and tight web integration, is an improved general model for scaling up collaborative open source software development in bioinformatics. AVAILABILITY: Biogem and modules are free and are OSS. Biogem runs on all systems that support recent versions of Ruby, including Linux, Mac OS X and Windows. Further information at http://www.biogems.info. A tutorial is available at http://www.biogems.info/howto.html CONTACT: [email protected].

In 2011, the IEEE VisWeek conferences inaugurated a symposium on Biological Data Visualization. Like other domain-oriented Vis symposia, this symposium's purpose was to explore the unique characteristics and requirements of visualization within the domain, and to enhance both the Visualization and Bio/Life-Sciences communities by pushing Biological data sets and domain understanding into the Visualization community, and well-informed Visualization solutions back to the Biological community. Amongst several other activities, the BioVis symposium created a data analysis and visualization contest. Unlike many contests in other venues, where the purpose is primarily to allow entrants to demonstrate tour-de-force programming skills on sample problems with known solutions, the BioVis contest was intended to whet the participants' appetites for a tremendously challenging biological domain, and simultaneously produce viable tools for a biological grand challenge domain with no extant solutions. For this purpose expression Quantitative Trait Locus (eQTL) data analysis was selected. In the BioVis 2011 contest, we provided contestants with a synthetic eQTL data set containing real biological variation, as well as a spiked-in gene expression interaction network influenced by single nucleotide polymorphism (SNP) DNA variation and a hypothetical disease model. Contestants were asked to elucidate the pattern of SNPs and interactions that predicted an individual's disease state. 9 teams competed in the contest using a mixture of methods, some analytical and others through visual exploratory methods. Independent panels of visualization and biological experts judged entries. Awards were given for each panel's favorite entry, and an overall best entry agreed upon by both panels. Three special mention awards were given for particularly innovative and useful aspects of those entries. And further recognition was given to entries that correctly answered a bonus question about how a proposed "gene therapy" change to a SNP might change an individual's disease status, which served as a calibration for each approaches' applicability to a typical domain question. In the future, BioVis will continue the data analysis and visualization contest, maintaining the philosophy of providing new challenging questions in open-ended and dramatically underserved Bio/Life Sciences domains.

BACKGROUND: The University of California, Santa Cruz (UCSC) genome database is among the most used sources of genomic annotation in human and other organisms. The database offers an excellent web-based graphical user interface (the UCSC genome browser) and several means for programmatic queries. A simple application programming interface (API) in a scripting language aimed at the biologist was however not yet available. Here, we present the Ruby UCSC API, a library to access the UCSC genome database using Ruby. RESULTS: The API is designed as a BioRuby plug-in and built on the ActiveRecord 3 framework for the object-relational mapping, making writing SQL statements unnecessary. The current version of the API supports databases of all organisms in the UCSC genome database including human, mammals, vertebrates, deuterostomes, insects, nematodes, and yeast.The API uses the bin index-if available-when querying for genomic intervals. The API also supports genomic sequence queries using locally downloaded *.2bit files that are not stored in the official MySQL database. The API is implemented in pure Ruby and is therefore available in different environments and with different Ruby interpreters (including JRuby). CONCLUSIONS: Assisted by the straightforward object-oriented design of Ruby and ActiveRecord, the Ruby UCSC API will facilitate biologists to query the UCSC genome database programmatically. The API is available through the RubyGem system. Source code and documentation are available at https://github.com/misshie/bioruby-ucsc-api/ under the Ruby license. Feedback and help is provided via the website at http://rubyucscapi.userecho.com/.

BACKGROUND: Elucidating the genotype-phenotype connection is one of the big challenges of modern molecular biology. To fully understand this connection, it is necessary to consider the underlying networks and the time factor. In this context of data deluge and heterogeneous information, visualization plays an essential role in interpreting complex and dynamic topologies. Thus, software that is able to bring the network, phenotypic and temporal information together is needed. Arena3D has been previously introduced as a tool that facilitates link discovery between processes. It uses a layered display to separate different levels of information while emphasizing the connections between them. We present novel developments of the tool for the visualization and analysis of dynamic genotype-phenotype landscapes. RESULTS: Version 2.0 introduces novel features that allow handling time course data in a phenotypic context. Gene expression levels or other measures can be loaded and visualized at different time points and phenotypic comparison is facilitated through clustering and correlation display or highlighting of impacting changes through time. Similarity scoring allows the identification of global patterns in dynamic heterogeneous data. In this paper we demonstrate the utility of the tool on two distinct biological problems of different scales. First, we analyze a medium scale dataset that looks at perturbation effects of the pluripotency regulator Nanog in murine embryonic stem cells. Dynamic cluster analysis suggests alternative indirect links between Nanog and other proteins in the core stem cell network. Moreover, recurrent correlations from the epigenetic to the translational level are identified. Second, we investigate a large scale dataset consisting of genome-wide knockdown screens for human genes essential in the mitotic process. Here, a potential new role for the gene lsm14a in cytokinesis is suggested. We also show how phenotypic patterning allows for extensive comparison and identification of high impact knockdown targets. CONCLUSIONS: We present a new visualization approach for perturbation screens with multiple phenotypic outcomes. The novel functionality implemented in Arena3D enables effective understanding and comparison of temporal patterns within morphological layers, to help with the system-wide analysis of dynamic processes. Arena3D is available free of charge for academics as a downloadable standalone application from: http://arena3d.org/.

UNLABELLED: The Ensembl database makes genomic features available via its Genome Browser. It is also possible to access the underlying data through a Perl API for advanced querying. We have developed a full-featured Ruby API to the Ensembl databases, providing the same functionality as the Perl interface with additional features. A single Ruby API is used to access different releases of the Ensembl databases and is also able to query multi-species databases. AVAILABILITY AND IMPLEMENTATION: Most functionality of the API is provided using the ActiveRecord pattern. The library depends on introspection to make it release independent. The API is available through the Rubygem system and can be installed with the command gem install ruby-ensembl-api.

SUMMARY: The BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby has components for sequence analysis, pathway analysis, protein modelling and phylogenetic analysis; it supports many widely used data formats and provides easy access to databases, external programs and public web services, including BLAST, KEGG, GenBank, MEDLINE and GO. BioRuby comes with a tutorial, documentation and an interactive environment, which can be used in the shell, and in the web browser. AVAILABILITY: BioRuby is free and open source software, made available under the Ruby license. BioRuby runs on all platforms that support Ruby, including Linux, Mac OS X and Windows. And, with JRuby, BioRuby runs on the Java Virtual Machine. The source code is available from http://www.bioruby.org/. CONTACT: [email protected]

The Ruby programming language has a lot to offer to any scientist with electronic data to process. Not only is the initial learning curve very shallow, but its reflection and meta-programming capabilities allow for the rapid creation of relatively complex applications while still keeping the code short and readable. This paper provides a gentle introduction to this scripting language for researchers without formal informatics training such as many wet-lab scientists. We hope this will provide such researchers an idea of how powerful a tool Ruby can be for their data management tasks and encourage them to learn more about it.