Holger Dinkel

Phospho.ELM: a database of phosphorylation sites--update 2011.

Phospho.ELM is a manually curated database of eukaryotic phosphorylation sites. The resource includes data collected from published literature as well as high-throughput data sets. The current release of Phospho.ELM (version 7.0, July 2007) contains 4078 phospho-protein sequences covering 12 025 phospho-serine, 2362 phospho-threonine and 2083 phospho-tyrosine sites. The entries provide information about the phosphorylated proteins and the exact position of known phosphorylated instances, the kinases responsible for the modification (where known) and links to bibliographic references. The database entries have hyperlinks to easily access further information from UniProt, PubMed, SMART, ELM, MSD as well as links to the protein interaction databases MINT and STRING. A new BLAST search tool, complementary to retrieval by keyword and UniProt accession number, allows users to submit a protein query (by sequence or UniProt accession) to search against the curated data set of phosphorylated peptides. Phospho.ELM is available on line at: http://phospho.elm.eu.org.The Phospho.ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomic analyses. The resource has been actively developed for more than 7 years and currently comprises 42 574 serine, threonine and tyrosine non-redundant phosphorylation sites. Several new features have been implemented, such as structural disorder/order and accessibility information and a conservation score. Additionally, the conservation of the phosphosites can now be visualized directly on the multiple sequence alignment used for the score calculation. Finally, special emphasis has been put on linking to external resources such as interaction networks and other databases.

ELM—the database of eukaryotic linear motifs

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

The eukaryotic linear motif resource ELM: 10 years and counting

The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains ∼200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways.

ELM 2016—data update and new functionality of the eukaryotic linear motif resource

The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances, manually curated from more than 2400 scientific publications. In addition, more data have been made available as individually searchable pages and are downloadable in various formats.

Short Linear Motifs: Ubiquitous and Functionally Diverse Protein Interaction Modules Directing Cell Regulation

Interaction Modules Directing Cell Regulation Kim Van Roey,† Bora Uyar,† Robert J. Weatheritt,‡ Holger Dinkel,† Markus Seiler,† Aidan Budd,† Toby J. Gibson,† and Norman E. Davey*,†,§ †Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany ‡MRC Laboratory of Molecular Biology (LMB), Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom Department of Physiology, University of California, San Francisco, San Francisco, California 94143, United States

The switches.ELM Resource: A Compendium of Conditional Regulatory Interaction Interfaces

A resource centered on short linear motifs provides a repository and exploratory tool for conditional protein interactions. Investigating Biological Switches Pre- and posttranslational mechanisms change the activity of proteins and can alter the functional interaction between them, thereby altering the physiological outcome of cellular signals. Van Roey et al. developed an online database and tool, “switches.ELM,” that contains a repository of experimentally validated mechanisms that dynamically regulate the functional states of short linear motifs (SLiMs), sites of protein-ligand binding, and rules for how these motifs function as cellular switches. Thus, the switches.ELM resource enables analysis of how protein interactions function in cellular decision-making. Short linear motifs (SLiMs) are protein interaction sites that play an important role in cell regulation by controlling protein activity, localization, and local abundance. The functionality of a SLiM can be modulated in a context-dependent manner to induce a gain, loss, or exchange of binding partners, which will affect the function of the SLiM-containing protein. As such, these conditional interactions underlie molecular decision-making in cell signaling. We identified multiple types of pre- and posttranslational switch mechanisms that can regulate the function of a SLiM and thereby control its interactions. The collected examples of experimentally characterized SLiM-based switch mechanisms were curated in the freely accessible switches.ELM resource (http://switches.elm.eu.org). On the basis of these examples, we defined and integrated rules to analyze SLiMs for putative regulatory switch mechanisms. We applied these rules to known validated SLiMs, providing evidence that more than half of these are likely to be pre- or posttranslationally regulated. In addition, we showed that posttranslationally modified sites are enriched around SLiMs, which enables cooperative and integrative regulation of protein interaction interfaces. We foresee switches.ELM complementing available resources to extend our knowledge of the molecular mechanisms underlying cell signaling.

iELM—a web server to explore short linear motif-mediated interactions

The recent expansion in our knowledge of protein–protein interactions (PPIs) has allowed the annotation and prediction of hundreds of thousands of interactions. However, the function of many of these interactions remains elusive. The interactions of Eukaryotic Linear Motif (iELM) web server provides a resource for predicting the function and positional interface for a subset of interactions mediated by short linear motifs (SLiMs). The iELM prediction algorithm is based on the annotated SLiM classes from the Eukaryotic Linear Motif (ELM) resource and allows users to explore both annotated and user-generated PPI networks for SLiM-mediated interactions. By incorporating the annotated information from the ELM resource, iELM provides functional details of PPIs. This can be used in proteomic analysis, for example, to infer whether an interaction promotes complex formation or degradation. Furthermore, details of the molecular interface of the SLiM-mediated interactions are also predicted. This information is displayed in a fully searchable table, as well as graphically with the modular architecture of the participating proteins extracted from the UniProt and Phospho.ELM resources. A network figure is also presented to aid the interpretation of results. The iELM server supports single protein queries as well as large-scale proteomic submissions and is freely available at http://i.elm.eu.org.

The Open Science Peer Review Oath

One of the foundations of the scientific method is to be able to reproduce experiments and corroborate the results of research that has been done before. However, with the increasing complexities of new technologies and techniques, coupled with the specialisation of experiments, reproducing research findings has become a growing challenge. Clearly, scientific methods must be conveyed succinctly, and with clarity and rigour, in order for research to be reproducible. Here, we propose steps to help increase the transparency of the scientific method and the reproducibility of research results: specifically, we introduce a peer-review oath and accompanying manifesto. These have been designed to offer guidelines to enable reviewers (with the minimum friction or bias) to follow and apply open science principles, and support the ideas of transparency, reproducibility and ultimately greater societal impact. Introducing the oath and manifesto at the stage of peer review will help to check that the research being published includes everything that other researchers would need to successfully repeat the work. Peer review is the lynchpin of the publishing system: encouraging the community to consciously (and conscientiously) uphold these principles should help to improve published papers, increase confidence in the reproducibility of the work and, ultimately, provide strategic benefits to authors and their institutions.

Ten simple rules for organizing an unconference.

An academic conference is a traditional platform for researchers and professionals to network and learn about recent developments and trends in a particular academic field [1–4]. Typically, the organizing committees and sponsors decide the main theme and sub-topics of the conference and select the presenters based on peer-reviewed papers [5]. The selected speakers usually share their research with a large audience by means of presentations and posters. However, the most stimulating discussions generally take place over coffee breaks when attendees can interact with each other and discuss various topics, including their own research interests, in a more informal manner [1, 6, 7], while expanding their own professional networks. An emphasis on facilitating such informal/networking interactions is a central focus of “unconventional conferences”—or “unconferences.” While many people may not yet have taken part in an unconference, the concept has been around for more than two decades. Events with unconference formats, beginning as early as 1985, include Open Space Technology, Foo Camp, BarCamp, Birds of a Feather, EdCamp, ScienceOnline, and many others. The success of these events has made the unconference format increasingly popular and widely known [8–11]. Unlike traditional conferences, an unconference is a participant-oriented meeting where the attendees decide on the agenda, discussion topics, workshops, and, often, even the time and venues. The informal and flexible program allows participants to suggest topics of their own interest and choose sessions accordingly. The format provides an excellent opportunity for researchers from diverse disciplines to work collaboratively on topics of common interest. The overarching goal for most unconferences is to prioritize conversation over presentation. In other words, the content for a session does not come from a select number of individuals at the front of the room, but is generated by all the attendees within the room, and, as such, every participant has an important role. Advantages of the unconference format include: a focus on topics that are relevant to the attendees (because they suggested them), an opportunity for teamwork development, flexibility of schedule, and an emphasis on contributions from every participant. The relationships built during an unconference often continue well past the event. The interactions can lead to productive collaborations, professional development opportunities, and a network of resources and are very effective at building a community amongst participants. The unconference format, therefore, gives participants experience in working together, and this can change how they think about their day-to-day work. A range of articles offer tips and advice for organizing and delivering aspects of scientific conferences and meetings or observations on features of successful meetings [5, 12, 13], including several from the PLOS Computational Biology “Ten Simple Rules” collection [14–16]. While the rules presented in this article are of particular relevance to the organization of unconferences, several of these points are also useful and complementary guidelines for organizing other kinds of events.

Biggest challenges in bioinformatics

The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to discuss the ‘Biggest Challenges in Bioinformatics’ in a ‘World Café’ style event.