As with many other aspects of the modern world, in healthcare, the explosion of data and resources opens new opportunities for the development of added-value services. Still, a number of specific conditions on this domain greatly hinders these developments, including ethical and legal issues, fragmentation of the relevant data in different locations, and a level of (meta)data complexity that requires great expertise across technical, clinical, and biological domains. We propose the Patient Dossier paradigm as a way to organize new innovative healthcare services that sorts the current limitations. The Patient Dossier conceptual framework identifies the different issues and suggests how they can be tackled in a safe, efficient, and responsible way while opening options for independent development for different players in the healthcare sector. An initial implementation of the Patient Dossier concepts in the Rbbt framework is available as open-source at https://github.com/mikisvaz and https://github.com/Rbbt-Workflows.

MOTIVATION: Drug synergies are sought to identify combinations of drugs particularly beneficial. User-friendly software solutions that can assist analysis of large-scale datasets are required. RESULTS: CImbinator is a web-service that can aid in batch-wise and in-depth analyzes of data from small-scale and large-scale drug combination screens. CImbinator offers to quantify drug combination effects, using both the commonly employed median effect equation, as well as advanced experimental mathematical models describing dose response relationships. AVAILABILITY AND IMPLEMENTATION: CImbinator is written in Ruby and R. It uses the R package drc for advanced drug response modeling. CImbinator is available at http://cimbinator.bioinfo.cnio.es , the source-code is open and available at https://github.com/Rbbt-Workflows/combination_index . A Docker image is also available at https://hub.docker.com/r/mikisvaz/rbbt-ci_mbinator/ . CONTACT: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: The interpretation of cancer-related single-nucleotide variants (SNVs) considering the protein features they affect, such as known functional sites, protein-protein interfaces, or relation with already annotated mutations, might complement the annotation of genetic variants in the analysis of NGS data. Current tools that annotate mutations fall short on several aspects, including the ability to use protein structure information or the interpretation of mutations in protein complexes. RESULTS: We present the Structure-PPi system for the comprehensive analysis of coding SNVs based on 3D protein structures of protein complexes. The 3D repository used, Interactome3D, includes experimental and modeled structures for proteins and protein-protein complexes. Structure-PPi annotates SNVs with features extracted from UniProt, InterPro, APPRIS, dbNSFP and COSMIC databases. We illustrate the usefulness of Structure-PPi with the interpretation of 1 027 122 non-synonymous SNVs from COSMIC and the 1000G Project that provides a collection of ∼172 700 SNVs mapped onto the protein 3D structure of 8726 human proteins (43.2% of the 20 214 SwissProt-curated proteins in UniProtKB release 2014_06) and protein-protein interfaces with potential functional implications. AVAILABILITY AND IMPLEMENTATION: Structure-PPi, along with a user manual and examples, isavailable at http://structureppi.bioinfo.cnio.es/Structure, the code for local installations at https://github.com/Rbbt-Workflows

MOTIVATION: Chemical named entity recognition is used to automatically identify mentions to chemical compounds in text and is the basis for more elaborate information extraction. However, only a small number of applications are freely available to identify such mentions. Particularly challenging and useful is the identification of International Union of Pure and Applied Chemistry (IUPAC) chemical compounds, which due to the complex morphology of IUPAC names requires more advanced techniques than that of brand names. RESULTS: We present CheNER, a tool for automated identification of systematic IUPAC chemical mentions. We evaluated different systems using an established literature corpus to show that CheNER has a superior performance in identifying IUPAC names specifically, and that it makes better use of computational resources. AVAILABILITY AND IMPLEMENTATION: http://metres.udl.cat/index.php/9-download/4-chener, http://chener.bioinfo.cnio.es/

BACKGROUND: Protein kinases are involved in relevant physiological functions and a broad number of mutations in this superfamily have been reported in the literature to affect protein function and stability. Unfortunately, the exploration of the consequences on the phenotypes of each individual mutation remains a considerable challenge. RESULTS: The wKinMut web-server offers direct prediction of the potential pathogenicity of the mutations from a number of methods, including our recently developed prediction method based on the combination of information from a range of diverse sources, including physicochemical properties and functional annotations from FireDB and Swissprot and kinase-specific characteristics such as the membership to specific kinase groups, the annotation with disease-associated GO terms or the occurrence of the mutation in PFAM domains, and the relevance of the residues in determining kinase subfamily specificity from S3Det. This predictor yields interesting results that compare favourably with other methods in the field when applied to protein kinases.Together with the predictions, wKinMut offers a number of integrated services for the analysis of mutations. These include: the classification of the kinase, information about associations of the kinase with other proteins extracted from iHop, the mapping of the mutations onto PDB structures, pathogenicity records from a number of databases and the classification of mutations in large-scale cancer studies. Importantly, wKinMut is connected with the SNP2L system that extracts mentions of mutations directly from the literature, and therefore increases the possibilities of finding interesting functional information associated to the studied mutations. CONCLUSIONS: wKinMut facilitates the exploration of the information available about individual mutations by integrating prediction approaches with the automatic extraction of information from the literature (text mining) and several state-of-the-art databases.wKinMut has been used during the last year for the analysis of the consequences of mutations in the context of a number of cancer genome projects, including the recent analysis of Chronic Lymphocytic Leukemia cases and is publicly available at http://wkinmut.bioinfo.cnio.es.

Although there is great promise in the benefits to be obtained by analyzing cancer genomes, numerous challenges hinder different stages of the process, from the problem of sample preparation and the validation of the experimental techniques, to the interpretation of the results. This chapter specifically focuses on the technical issues associated with the bioinformatics analysis of cancer genome data. The main issues addressed are the use of database and software resources, the use of analysis workflows and the presentation of clinically relevant action items. We attempt to aid new developers in the field by describing the different stages of analysis and discussing current approaches, as well as by providing practical advice on how to access and use resources, and how to implement recommendations. Real cases from cancer genome projects are used as examples.

BACKGROUND: Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them. RESULTS: A total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35%) the macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of 55%. CONCLUSIONS: The results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heterogeneity and different granularity of method term concepts encountered in the ontology. However, combining the sophisticated techniques developed by the participants with supporting evidence strings derived from the articles for human interpretation could result in practical modules for biological annotation workflows.