BackgroundNext Generation Sequencing (NGS) is playing a key role in therapeutic decision making for the cancer prognosis and treatment. The NGS technologies are producing a massive amount of sequencing datasets. Often, these datasets are published from the isolated and different sequencing facilities. Consequently, the process of sharing and aggregating multisite sequencing datasets are thwarted by issues such as the need to discover relevant data from different sources, built scalable repositories, the automation of data linkage, the volume of the data, efficient querying mechanism, and information rich intuitive visualisation.ResultsWe present an approach to link and query different sequencing datasets (TCGA, COSMIC, REACTOME, KEGG and GO) to indicate risks for four cancer types – Ovarian Serous Cystadenocarcinoma (OV), Uterine Corpus Endometrial Carcinoma (UCEC), Uterine Carcinosarcoma (UCS), Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) – covering the 16 healthy tissue-specific genes from Illumina Human Body Map 2.0. The differentially expressed genes from Illumina Human Body Map 2.0 are analysed together with the gene expressions reported in COSMIC and TCGA repositories leading to the discover of potential biomarkers for a tissue-specific cancer.ConclusionWe analyse the tissue expression of genes, copy number variation (CNV), somatic mutation, and promoter methylation to identify associated pathways and find novel biomarkers. We discovered twenty (20) mutated genes and three (3) potential pathways causing promoter changes in different gynaecological cancer types. We propose a data-interlinked platform called BIOOPENER that glues together heterogeneous cancer and biomedical repositories. The key approach is to find correspondences (or data links) among genetic, cellular and molecular features across isolated cancer datasets giving insight into cancer progression from normal to diseased tissues. The proposed BIOOPENER platform enriches mutations by filling in missing links from TCGA, COSMIC, REACTOME, KEGG and GO datasets and provides an interlinking mechanism to understand cancer progression from normal to diseased tissues with pathway components, which in turn helped to map mutations, associated phenotypes, pathways, and mechanism.

BackgroundSeveral query federation engines have been proposed for accessing public Linked Open Data sources. However, in many domains, resources are sensitive and access to these resources is tightly controlled by stakeholders; consequently, privacy is a major concern when federating queries over such datasets. In the Healthcare and Life Sciences (HCLS) domain real-world datasets contain sensitive statistical information: strict ownership is granted to individuals working in hospitals, research labs, clinical trial organisers, etc. Therefore, the legal and ethical concerns on (i) preserving the anonymity of patients (or clinical subjects); and (ii) respecting data ownership through access control; are key challenges faced by the data analytics community working within the HCLS domain. Likewise statistical data play a key role in the domain, where the RDF Data Cube Vocabulary has been proposed as a standard format to enable the exchange of such data. However, to the best of our knowledge, no existing approach has looked to optimise federated queries over such statistical data.ResultsWe present SAFE: a query federation engine that enables policy-aware access to sensitive statistical datasets represented as RDF data cubes. SAFE is designed specifically to query statistical RDF data cubes in a distributed setting, where access control is coupled with source selection, user profiles and their access rights. SAFE proposes a join-aware source selection method that avoids wasteful requests to irrelevant and unauthorised data sources. In order to preserve anonymity and enforce stricter access control, SAFE’s indexing system does not hold any data instances—it stores only predicates and endpoints. The resulting data summary has a significantly lower index generation time and size compared to existing engines, which allows for faster updates when sources change.ConclusionsWe validate the performance of the system with experiments over real-world datasets provided by three clinical organisations as well as legacy linked datasets. We show that SAFE enables granular graph-level access control over distributed clinical RDF data cubes and efficiently reduces the source selection and overall query execution time when compared with general-purpose SPARQL query federation engines in the targeted setting.

Data workflow systems (DWFSs) enable bioinformatics researchers to combine components for data access and data analytics, and to share the final data analytics approach with their collaborators. Increasingly, such systems have to cope with large-scale data, such as full genomes (about 200 GB each), public fact repositories (about 100 TB of data) and 3D imaging data at even larger scales. As moving the data becomes cumbersome, the DWFS needs to embed its processes into a cloud infrastructure, where the data are already hosted. As the standardized public data play an increasingly important role, the DWFS needs to comply with Semantic Web technologies. This advancement to DWFS would reduce overhead costs and accelerate the progress in bioinformatics research based on large-scale data and public resources, as researchers would require less specialized IT knowledge for the implementation. Furthermore, the high data growth rates in bioinformatics research drive the demand for parallel and distributed computing, which then imposes a need for scalability and high-throughput capabilities onto the DWFS. As a result, requirements for data sharing and access to public knowledge bases suggest that compliance of the DWFS with Semantic Web standards is necessary. In this article, we will analyze the existing DWFS with regard to their capabilities toward public open data use as well as large-scale computational and human interface requirements. We untangle the parameters for selecting a preferable solution for bioinformatics research with particular consideration to using cloud services and Semantic Web technologies. Our analysis leads to research guidelines and recommendations toward the development of future DWFS for the bioinformatics research community.

The study of genetic variants (GVs) can help find correlating population groups and to identify cohorts that are predisposed to common diseases and explain differences in disease susceptibility and how patients react to drugs. Machine learning techniques are increasingly being applied to identify interacting GVs to understand their complex phenotypic traits. Since the performance of a learning algorithm not only depends on the size and nature of the data but also on the quality of underlying representation, deep neural networks (DNNs) can learn non-linear mappings that allow transforming GVs data into more clustering and classification friendly representations than manual feature selection. In this paper, we propose convolutional embedded networks (CEN) in which we combine two DNN architectures called convolutional embedded clustering (CEC) and convolutional autoencoder (CAE) classifier for clustering individuals and predicting geographic ethnicity based on GVs, respectively. We employed CAE-based representation learning to 95 million GVs from the '1000 genomes' (covering 2,504 individuals from 26 ethnic origins) and 'Simons genome diversity' (covering 279 individuals from 130 ethnic origins) projects. Quantitative and qualitative analyses with a focus on accuracy and scalability show that our approach outperforms state-of-the-art approaches such as VariantSpark and ADMIXTURE. In particular, CEC can cluster targeted population groups in 22 hours with an adjusted rand index (ARI) of 0.915, the normalized mutual information (NMI) of 0.92, and the clustering accuracy (ACC) of 89 percent. Contrarily, the CAE classifier can predict the geographic ethnicity of unknown samples with an F1 and Mathews correlation coefficient (MCC) score of 0.9004 and 0.8245, respectively. Further, to provide interpretations of the predictions, we identify significant biomarkers using gradient boosted trees (GBT) and SHapley Additive exPlanations (SHAP). Overall, our approach is transparent and faster than the baseline methods, and scalable for 5 to 100 percent of the full human genome.

Data retrieval systems are facing a paradigm shift due to the proliferation of specialized data storage engines (SQL, NoSQL, Column Stores, MapReduce, Data Stream, and Graph) supported by varied data models (CSV, JSON, RDB, RDF, and XML). One immediate consequence of this paradigm shift results into data bottleneck over the web; which means, web applications are unable to retrieve data with the intensity at which data are being generated from different facilities. Especially in the genomics and healthcare verticals, data are growing from petascale to exascale, and biomedical stakeholders are expecting seamless retrieval of these data over the web. In this paper, we argue that the bottleneck over the web can be reduced by minimizing the costly data conversion process and delegating query performance and processing loads to the specialized data storage engines over their native data models. We propose a web-based query federation mechanism-called PolyWeb-that unifies query answering over multiple native data models (CSV, RDB, and RDF). We emphasize two main challenges of query federation over native data models: 1) devise a method to select prospective data sources-with different underlying data models-that can satisfy a given query and 2) query optimization, join, and execution over different data models. We demonstrate PolyWeb on a cancer genomics use case, where it is often the case that a description of biological and chemical entities (e.g., gene, disease, drug, and pathways) spans across multiple data models and respective storage engines. In order to assess the benefits and limitations of evaluating queries over native data models, we evaluate PolyWeb with the state-of-the-art query federation engines in terms of result completeness, source selection, and overall query execution time.