Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery

Motivation: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult. Results: We present SignaLink, a database containing 8 major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster, and humans. Based on 170 review and approx. 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the 8 pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery. Conclusions: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease and underscore its importance in network-based drug target selection. Availability: http://SignaLink.orgComment: 9 pages, 4 figures, 2 tables and a supplementary info with 5 Figures and 13 Table

Theory and Practice of Data Citation

Citations are the cornerstone of knowledge propagation and the primary means of assessing the quality of research, as well as directing investments in science. Science is increasingly becoming "data-intensive", where large volumes of data are collected and analyzed to discover complex patterns through simulations and experiments, and most scientific reference works have been replaced by online curated datasets. Yet, given a dataset, there is no quantitative, consistent and established way of knowing how it has been used over time, who contributed to its curation, what results have been yielded or what value it has. The development of a theory and practice of data citation is fundamental for considering data as first-class research objects with the same relevance and centrality of traditional scientific products. Many works in recent years have discussed data citation from different viewpoints: illustrating why data citation is needed, defining the principles and outlining recommendations for data citation systems, and providing computational methods for addressing specific issues of data citation. The current panorama is many-faceted and an overall view that brings together diverse aspects of this topic is still missing. Therefore, this paper aims to describe the lay of the land for data citation, both from the theoretical (the why and what) and the practical (the how) angle.Comment: 24 pages, 2 tables, pre-print accepted in Journal of the Association for Information Science and Technology (JASIST), 201

SBML models and MathSBML

MathSBML is an open-source, freely-downloadable Mathematica package that facilitates working with Systems Biology Markup Language (SBML) models. SBML is a toolneutral,computer-readable format for representing models of biochemical reaction networks, applicable to metabolic networks, cell-signaling pathways, genomic regulatory networks, and other modeling problems in systems biology that is widely supported by the systems biology community. SBML is based on XML, a standard medium for representing and transporting data that is widely supported on the internet as well as in computational biology and bioinformatics. Because SBML is tool-independent, it enables model transportability, reuse, publication and survival. In addition to MathSBML, a number of other tools that support SBML model examination and manipulation are provided on the sbml.org website, including libSBML, a C/C++ library for reading SBML models; an SBML Toolbox for MatLab; file conversion programs; an SBML model validator and visualizer; and SBML specifications and schemas. MathSBML enables SBML file import to and export from Mathematica as well as providing an API for model manipulation and simulation

An Introduction to Programming for Bioscientists: A Python-based Primer

Computing has revolutionized the biological sciences over the past several decades, such that virtually all contemporary research in the biosciences utilizes computer programs. The computational advances have come on many fronts, spurred by fundamental developments in hardware, software, and algorithms. These advances have influenced, and even engendered, a phenomenal array of bioscience fields, including molecular evolution and bioinformatics; genome-, proteome-, transcriptome- and metabolome-wide experimental studies; structural genomics; and atomistic simulations of cellular-scale molecular assemblies as large as ribosomes and intact viruses. In short, much of post-genomic biology is increasingly becoming a form of computational biology. The ability to design and write computer programs is among the most indispensable skills that a modern researcher can cultivate. Python has become a popular programming language in the biosciences, largely because (i) its straightforward semantics and clean syntax make it a readily accessible first language; (ii) it is expressive and well-suited to object-oriented programming, as well as other modern paradigms; and (iii) the many available libraries and third-party toolkits extend the functionality of the core language into virtually every biological domain (sequence and structure analyses, phylogenomics, workflow management systems, etc.). This primer offers a basic introduction to coding, via Python, and it includes concrete examples and exercises to illustrate the language's usage and capabilities; the main text culminates with a final project in structural bioinformatics. A suite of Supplemental Chapters is also provided. Starting with basic concepts, such as that of a 'variable', the Chapters methodically advance the reader to the point of writing a graphical user interface to compute the Hamming distance between two DNA sequences.Comment: 65 pages total, including 45 pages text, 3 figures, 4 tables, numerous exercises, and 19 pages of Supporting Information; currently in press at PLOS Computational Biolog

Chemical information matters: an e-Research perspective on information and data sharing in the chemical sciences

Recently, a number of organisations have called for open access to scientific information and especially to the data obtained from publicly funded research, among which the Royal Society report and the European Commission press release are particularly notable. It has long been accepted that building research on the foundations laid by other scientists is both effective and efficient. Regrettably, some disciplines, chemistry being one, have been slow to recognise the value of sharing and have thus been reluctant to curate their data and information in preparation for exchanging it. The very significant increases in both the volume and the complexity of the datasets produced has encouraged the expansion of e-Research, and stimulated the development of methodologies for managing, organising, and analysing "big data". We review the evolution of cheminformatics, the amalgam of chemistry, computer science, and information technology, and assess the wider e-Science and e-Research perspective. Chemical information does matter, as do matters of communicating data and collaborating with data. For chemistry, unique identifiers, structure representations, and property descriptors are essential to the activities of sharing and exchange. Open science entails the sharing of more than mere facts: for example, the publication of negative outcomes can facilitate better understanding of which synthetic routes to choose, an aspiration of the Dial-a-Molecule Grand Challenge. The protagonists of open notebook science go even further and exchange their thoughts and plans. We consider the concepts of preservation, curation, provenance, discovery, and access in the context of the research lifecycle, and then focus on the role of metadata, particularly the ontologies on which the emerging chemical Semantic Web will depend. Among our conclusions, we present our choice of the "grand challenges" for the preservation and sharing of chemical information

A Unified Forensics Analysis Approach to Digital Investigation

Digital forensics is now essential in addressing cybercrime and cyber-enabled crime but potentially it can have a role in almost every other type of crime. Given technology's continuous development and prevalence, the widespread adoption of technologies among society and the subsequent digital footprints that exist, the analysis of these technologies can help support investigations. The abundance of interconnected technologies and telecommunication platforms has significantly changed the nature of digital evidence. Subsequently, the nature and characteristics of digital forensic cases involve an enormous volume of data heterogeneity, scattered across multiple evidence sources, technologies, applications, and services. It is indisputable that the outspread and connections between existing technologies have raised the need to integrate, harmonise, unify and correlate evidence across data sources in an automated fashion. Unfortunately, the current state of the art in digital forensics leads to siloed approaches focussed upon specific technologies or support of a particular part of digital investigation. Due to this shortcoming, the digital investigator examines each data source independently, trawls through interconnected data across various sources, and often has to conduct data correlation manually, thus restricting the digital investigator’s ability to answer high-level questions in a timely manner with a low cognitive load. Therefore, this research paper investigates the limitations of the current state of the art in the digital forensics discipline and categorises common investigation crimes with the necessary corresponding digital analyses to define the characteristics of the next-generation approach. Based on these observations, it discusses the future capabilities of the next-generation unified forensics analysis tool (U-FAT), with a workflow example that illustrates data unification, correlation and visualisation processes within the proposed method.</jats:p

SignaLink 2 - a signaling pathway resource with multi-layered regulatory networks.

BACKGROUND Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor. DESCRIPTION We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., BioPAX, Cytoscape, SBML). Non-profit users can access SignaLink 2 free of charge at http://SignaLink.org. CONCLUSIONS With SignaLink 2 as a single resource, users can effectively analyze signaling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signaling processes. This integrated resource allows the systems-level examination of how cross-talks and signaling flow are regulated, as well as provide data for cross-species comparisons and drug discovery analyses