Motivation: Improvement of sequencing technologies and data processing pipelines is rapidly providing sequencing data, with associated high-level features, of many individual genomes in multiple biological and clinical conditions. They allow for data-driven genomic, transcriptomic and epigenomic characterizations, but require state-of-the-art ‘big data’ computing strategies, with abstraction levels beyond available tool capabilities. Results: We propose a high-level, declarative GenoMetric Query Language (GMQL) and a toolkit for its use. GMQL operates downstream of raw data preprocessing pipelines and supports queries over thousands of heterogeneous datasets and samples; as such it is key to genomic ‘big data’ analysis. GMQL leverages a simple data model that provides both abstractions of genomic region data and associated experimental, biological and clinical metadata and interoperability between many data formats. Based on Hadoop framework and Apache Pig platform, GMQL ensures high scalability, expressivity, flexibility and simplicity of use, as demonstrated by several biological query examples on ENCODE and TCGA datasets. Availability and implementation: The GMQL toolkit is freely available for non-commercial use at http://www.bioinformatics.deib.polimi.it/GMQL/. Contact:marco.masseroli@polimi.it Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: We previously proposed a paradigm shift in genomic data management, based on the Genomic Data Model (GDM) for mediating existing data formats and on the GenoMetric Query Language (GMQL) for supporting, at a high level of abstraction, data extraction and the most common data-driven computations required by tertiary data analysis of Next Generation Sequencing datasets. Here, we present a new GMQL-based system with enhanced accessibility, portability, scalability and performance. Results: The new system has a well-designed modular architecture featuring: (i) an intermediate representation supporting many different implementations (including Spark, Flink and SciDB); (ii) a high-level technology-independent repository abstraction, supporting different repository technologies (e.g., local file system, Hadoop File System, database or others); (iii) several system interfaces, including a user-friendly Web-based interface, a Web Service interface, and a programmatic interface for Python language. Biological use case examples, using public ENCODE, Roadmap Epigenomics and TCGA datasets, demonstrate the relevance of our work. Availability and implementation: The GMQL system is freely available for non-commercial use as open source project at: http://www.bioinformatics.deib.polimi.it/GMQLsystem/. Supplementary information: Supplementary data are available at Bioinformatics online.

Classical drug design methodologies are hugely costly and time-consuming, with approximately 85% of the new proposed molecules failing in the first three phases of the FDA drug approval process. Thus, strategies to find alternative indications for already approved drugs that leverage computational methods are of crucial relevance. We previously demonstrated the efficacy of the Non-negative Matrix Tri-Factorization, a method that allows exploiting both data integration and machine learning, to infer novel indications for approved drugs. In this work, we present an innovative enhancement of the NMTF method that consists of a shortest-path evaluation of drug-protein pairs using the protein-to-protein interaction network. This approach allows inferring novel protein targets that were never considered as drug targets before, increasing the information fed to the NMTF method. Indeed, this novel advance enables the investigation of drug-centric predictions, simultaneously identifying therapeutic classes, protein targets and diseases associated with a particular drug. To test our methodology, we applied the NMTF and shortest-path enhancement methods to an outdated collection of data and compared the predictions against the most updated version, obtaining very good performance, with an Average Precision Score of 0.82. The data enhancement strategy allowed increasing the number of putative protein targets from 3,691 to 15,295, while the predictive performance of the method is slightly increased. Finally, we also validated our top-scored predictions according to the literature, finding relevant confirmation of predicted interactions between drugs and protein targets, as well as of predicted annotations between drugs and both therapeutic classes and diseases.

Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments.

Thousands of new experimental datasets are becoming available every day; in many cases, they are produced within the scope of large cooperative efforts, involving a variety of laboratories spread all over the world, and typically open for public use. Although the potential collective amount of available information is huge, the effective combination of such public sources is hindered by data heterogeneity, as the datasets exhibit a wide variety of notations and formats, concerning both experimental values and metadata. Thus, data integration is becoming a fundamental activity, to be performed prior to data analysis and biological knowledge discovery, consisting of subsequent steps of data extraction, normalization, matching and enrichment; once applied to heterogeneous data sources, it builds multiple perspectives over the genome, leading to the identification of meaningful relationships that could not be perceived by using incompatible data formats. In this paper, we first describe a technological pipeline from data production to data integration; we then propose a taxonomy of genomic data players (based on the distinction between contributors, repository hosts, consortia, integrators and consumers) and apply the taxonomy to describe about 30 important players in genomic data management. We specifically focus on the integrator players and analyse the issues in solving the genomic data integration challenges, as well as evaluate the computational environments that they provide to follow up data integration by means of visualization and analysis tools.