Interactions of proteins regulate signaling, catalysis, gene expression and many other cellular functions. Therefore, characterizing the entire human interactome is a key effort in current proteomics research. This challenge is complicated by the dynamic nature of protein-protein interactions (PPIs), which are conditional on the cellular context: both interacting proteins must be expressed in the same cell and localized in the same organelle to meet. Additionally, interactions underlie a delicate control of signaling pathways, e.g. by post-translational modifications of the protein partners - hence, many diseases are caused by the perturbation of these mechanisms. Despite the high degree of cell-state specificity of PPIs, many interactions are measured under artificial conditions (e.g. yeast cells are transfected with human genes in yeast two-hybrid assays) or even if detected in a physiological context, this information is missing from the common PPI databases. To overcome these problems, we developed a method that assigns context information to PPIs inferred from various attributes of the interacting proteins: gene expression, functional and disease annotations, and inferred pathways. We demonstrate that context consistency correlates with the experimental reliability of PPIs, which allows us to generate high-confidence tissue- and function-specific subnetworks. We illustrate how these context-filtered networks are enriched in bona fide pathways and disease proteins to prove the ability of context-filters to highlight meaningful interactions with respect to various biological questions. We use this approach to study the lung-specific pathways used by the influenza virus, pointing to IRAK1, BHLHE40 and TOLLIP as potential regulators of influenza virus pathogenicity, and to study the signalling pathways that play a role in Alzheimer's disease, identifying a pathway involving the altered phosphorylation of the Tau protein. Finally, we provide the annotated human PPI network via a web frontend that allows the construction of context-specific networks in several ways.

The cross-disciplinary nature of bioinformatics entails co-evolution with other biomedical disciplines, whereby some bioinformatics applications become popular in certain disciplines and, in turn, these disciplines influence the focus of future bioinformatics development efforts. We observe here that the growth of computational approaches within various biomedical disciplines is not merely a reflection of a general extended usage of computers and the Internet, but due to the production of useful bioinformatics databases and methods for the rest of the biomedical scientific community. We have used the abstracts stored both in the MEDLINE database of biomedical literature and in NIH-funded project grants, to quantify two effects. First, we examine the biomedical literature as a whole and find that the use of computational methods has become increasingly prevalent across biomedical disciplines over the past three decades, while use of databases and the Internet have been rapidly increasing over the past decade. Second, we study the recent trends in the use of bioinformatics topics. We observe that molecular sequence databases are a widely adopted contribution in biomedicine from the field of bioinformatics, and that microarray analysis is one of the major new topics engaged by the bioinformatics community. Via this analysis, we were able to identify areas of rapid growth in the use of informatics to aid in curriculum planning, development of computational infrastructure and strategies for workforce education and funding.

BACKGROUND: The annotations of Affymetrix DNA microarray probe sets with Gene Ontology terms are carefully selected for correctness. This results in very accurate but incomplete annotations which is not always desirable for microarray experiment evaluation. RESULTS: Here we present a protocol to amplify the set of Gene Ontology annotations associated to Affymetrix DNA microarray probe sets using information from related databases. CONCLUSION: Predicted novel annotations and the evidence producing them can be accessed at Probe2GO: http://www.ogic.ca/p2g. Scripts are available on demand.

BACKGROUND: DNA microarray probes are designed to match particular mRNA transcripts, often based on expressed sequences like ESTs, or cDNAs, many times incomplete. As a result, the relations between probes and genes can change as the sequence data are updated. However, it is frequent that the reported results of microarray analyses are given just as lists of genes without any reference to the underlying probes. RESULTS: We show for a particular commercial microarray design that the number of probes associated to some genes change with time. These changes concern approximately 5% of the probe sets across the history of annotation releases over a two year span. CONCLUSION: We recommend to report probe set identifiers when publishing microarray results, and to submit those analyses to microarray public databases to ensure that the interpretation of the data is updated with the latest set of annotations.

MOTIVATION: The description of genes in databases by keywords helps the non-specialist to quickly grasp the properties of a gene and increases the efficiency of computational tools that are applied to gene data (e.g. searching a gene database for sequences related to a particular biological process). However, the association of keywords to genes or protein sequences is a difficult process that ultimately implies examination of the literature related to a gene. RESULTS: To support this task, we present a procedure to derive keywords from the set of scientific abstracts related to a gene. Our system is based on the automated extraction of mappings between related terms from different databases using a model of fuzzy associations that can be applied with all generality to any pair of linked databases. We tested the system by annotating genes of the SWISS-PROT database with keywords derived from the abstracts linked to their entries (stored in the MEDLINE database of scientific references). The performance of the annotation procedure was much better for SWISS-PROT keywords (recall of 47%, precision of 68%) than for Gene Ontology terms (recall of 8%, precision of 67%). AVAILABILITY: The algorithm can be publicly accessed and used for the annotation of sequences through a web server at http://www.bork.embl.de/kat

BACKGROUND: To date, many of the methods for information extraction of biological information from scientific articles are restricted to the abstract of the article. However, full text articles in electronic version, which offer larger sources of data, are currently available. Several questions arise as to whether the effort of scanning full text articles is worthy, or whether the information that can be extracted from the different sections of an article can be relevant. RESULTS: In this work we addressed those questions showing that the keyword content of the different sections of a standard scientific article (abstract, introduction, methods, results, and discussion) is very heterogeneous. CONCLUSIONS: Although the abstract contains the best ratio of keywords per total of words, other sections of the article may be a better source of biologically relevant data.