SCOWLP: a web-based database for detailed characterization and visualization of protein interfaces

BACKGROUND: Currently there is a strong need for methods that help to obtain an accurate description of protein interfaces in order to be able to understand the principles that govern molecular recognition and protein function. Many of the recent efforts to computationally identify and characterize protein networks extract protein interaction information at atomic resolution from the PDB. However, they pay none or little attention to small protein ligands and solvent. They are key components and mediators of protein interactions and fundamental for a complete description of protein interfaces. Interactome profiling requires the development of computational tools to extract and analyze protein-protein, protein-ligand and detailed solvent interaction information from the PDB in an automatic and comparative fashion. Adding this information to the existing one on protein-protein interactions will allow us to better understand protein interaction networks and protein function. DESCRIPTION: SCOWLP (Structural Characterization Of Water, Ligands and Proteins) is a user-friendly and publicly accessible web-based relational database for detailed characterization and visualization of the PDB protein interfaces. The SCOWLP database includes proteins, peptidic-ligands and interface water molecules as descriptors of protein interfaces. It contains currently 74,907 protein interfaces and 2,093,976 residue-residue interactions formed by 60,664 structural units (protein domains and peptidic-ligands) and their interacting solvent. The SCOWLP web-server allows detailed structural analysis and comparisons of protein interfaces at atomic level by text query of PDB codes and/or by navigating a SCOP-based tree. It includes a visualization tool to interactively display the interfaces and label interacting residues and interface solvent by atomic physicochemical properties. SCOWLP is automatically updated with every SCOP release. CONCLUSION: SCOWLP enriches substantially the description of protein interfaces by adding detailed interface information of peptidic-ligands and solvent to the existing protein-protein interaction databases. SCOWLP may be of interest to many structural bioinformaticians. It provides a platform for automatic global mapping of protein interfaces at atomic level, representing a useful tool for classification of protein interfaces, protein binding comparative studies, reconstruction of protein complexes and understanding protein networks. The web-server with the database and its additional summary tables used for our analysis are available at

Biomedical word sense disambiguation with ontologies and metadata: automation meets accuracy

<p>Abstract</p> <p>Background</p> <p>Ontology term labels can be ambiguous and have multiple senses. While this is no problem for human annotators, it is a challenge to automated methods, which identify ontology terms in text. Classical approaches to word sense disambiguation use co-occurring words or terms. However, most treat ontologies as simple terminologies, without making use of the ontology structure or the semantic similarity between terms. Another useful source of information for disambiguation are metadata. Here, we systematically compare three approaches to word sense disambiguation, which use ontologies and metadata, respectively.</p> <p>Results</p> <p>The 'Closest Sense' method assumes that the ontology defines multiple senses of the term. It computes the shortest path of co-occurring terms in the document to one of these senses. The 'Term Cooc' method defines a log-odds ratio for co-occurring terms including co-occurrences inferred from the ontology structure. The 'MetaData' approach trains a classifier on metadata. It does not require any ontology, but requires training data, which the other methods do not. To evaluate these approaches we defined a manually curated training corpus of 2600 documents for seven ambiguous terms from the Gene Ontology and MeSH. All approaches over all conditions achieve 80% success rate on average. The 'MetaData' approach performed best with 96%, when trained on high-quality data. Its performance deteriorates as quality of the training data decreases. The 'Term Cooc' approach performs better on Gene Ontology (92% success) than on MeSH (73% success) as MeSH is not a strict is-a/part-of, but rather a loose is-related-to hierarchy. The 'Closest Sense' approach achieves on average 80% success rate.</p> <p>Conclusion</p> <p>Metadata is valuable for disambiguation, but requires high quality training data. Closest Sense requires no training, but a large, consistently modelled ontology, which are two opposing conditions. Term Cooc achieves greater 90% success given a consistently modelled ontology. Overall, the results show that well structured ontologies can play a very important role to improve disambiguation.</p> <p>Availability</p> <p>The three benchmark datasets created for the purpose of disambiguation are available in Additional file <supplr sid="S1">1</supplr>.</p> <suppl id="S1"> <title> <p>Additional file 1</p> </title> <text> <p><b>Benchmark datasets used in the experiments.</b> The three corpora (High quality/Low quantity corpus; Medium quality/Medium quantity corpus; Low quality/High quantity corpus) are given in the form of PubMed identifiers (PMID) for True/False cases for the 7 ambiguous terms examined (GO/MeSH/UMLS identifiers are also given).</p> </text> <file name="1471-2105-10-28-S1.txt"> <p>Click here for file</p> </file> </suppl

GoPubMed: Exploring Pubmed with Ontological Background Knowledge

With the ever increasing size of scientific literature, finding relevant documents and answering questions has become even more of a challenge. Recently, ontologies - hierarchical, controlled vocabularies - have been introduced to annotate genomic data. They can also improve the question answering and the selection of relevant documents in the literature search. Search engines such as GoPubMed.org use ontological background knowledge to give an overview over large query results and to help answering questions. We review the problems and solutions underlying these next generation intelligent search engines and give examples of the power of this new search paradigm

Agents in bioinformatics, computational and systems biology

The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meeting provided an opportunity for seeding collaborations between the agent and bioinformatics communities to develop a different (agent-based) approach of computational frameworks both for data analysis and management in bioinformatics and for systems modelling and simulation in computational and systems biology.The collaborations gave rise to applica- tions and integrated tools that we summarize and discuss in context of the state of the art in this area. We investigate on future challenges and argue that the field should still be explored from many perspectives ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages to be used by information agents, and to the adoption of agents for computational grid

GoPubMed: Ontology-based literature search for the life sciences

Background: Most of our biomedical knowledge is only accessible through texts. The biomedical literature grows exponentially and PubMed comprises over 18.000.000 literature abstracts. Recently much effort has been put into the creation of biomedical ontologies which capture biomedical facts. The exploitation of ontologies to explore the scientific literature is a new area of research. Motivation: When people search, they have questions in mind. Answering questions in a domain requires the knowledge of the terminology of that domain. Classical search engines do not provide background knowledge for the presentation of search results. Ontology annotated structured databases allow for data-mining. The hypothesis is that ontology annotated literature databases allow for text-mining. The central problem is to associate scientific publications with ontological concepts. This is a prerequisite for ontology-based literature search. The question then is how to answer biomedical questions using ontologies and a literature corpus. Finally the task is to automate bibliometric analyses on an corpus of scientific publications. Approach: Recent joint efforts on automatically extracting information from free text showed that the applied methods are complementary. The idea is to employ the rich terminological and relational information stored in biomedical ontologies to markup biomedical text documents. Based on established semantic links between documents and ontology concepts the goal is to answer biomedical question on a corpus of documents. The entirely annotated literature corpus allows for the first time to automatically generate bibliometric analyses for ontological concepts, authors and institutions. Results: This work includes a novel annotation framework for free texts with ontological concepts. The framework allows to generate recognition patterns rules from the terminological and relational information in an ontology. Maximum entropy models can be trained to distinguish the meaning of ambiguous concept labels. The framework was used to develop a annotation pipeline for PubMed abstracts with 27,863 Gene Ontology concepts. The evaluation of the recognition performance yielded a precision of 79.9% and a recall of 72.7% improving the previously used algorithm by 25,7% f-measure. The evaluation was done on a manually created (by the original authors) curation corpus of 689 PubMed abstracts with 18,356 curations of concepts. Methods to reason over large amounts of documents with ontologies were developed. The ability to answer questions with the online system was shown on a set of biomedical question of the TREC Genomics Track 2006 benchmark. This work includes the first ontology-based, large scale, online available, up-to-date bibliometric analysis for topics in molecular biology represented by GO concepts. The automatic bibliometric analysis is in line with existing, but often out-dated, manual analyses. Outlook: A number of promising continuations starting from this work have been spun off. A freely available online search engine has a growing user community. A spin-off company was funded by the High-Tech Gründerfonds which commercializes the new ontology-based search paradigm. Several off-springs of GoPubMed including GoWeb (general web search), Go3R (search in replacement, reduction, refinement methods for animal experiments), GoGene (search in gene/protein databases) are developed