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An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them. Ontologies are critical to support the types of big data analysis necessary for kidney precision medicine, where heterogeneous clinical, imaging and biopsy data from diverse sources must be combined to define a patient's phenotype. The development of two new ontologies - the Kidney Tissue Atlas Ontology and the Ontology of Precision Medicine and Investigation - will support the creation of the Kidney Tissue Atlas, which aims to provide a comprehensive molecular, cellular and anatomical map of the kidney. These ontologies will improve the annotation of kidney-relevant data, and eventually lead to new definitions of kidney disease in support of precision medicine.

Linked Data (LD) aims to achieve interconnected data by representing entities using Unified Resource Identifiers (URIs), and sharing information using Resource Description Frameworks (RDFs) and HTTP. Ontologies, which logically represent entities and relations in specific domains, are the basis of LD. Ontobee (http://www.ontobee.org/) is a linked ontology data server that stores ontology information using RDF triple store technology and supports query, visualization and linkage of ontology terms. Ontobee is also the default linked data server for publishing and browsing biomedical ontologies in the Open Biological Ontology (OBO) Foundry (http://obofoundry.org) library. Ontobee currently hosts more than 180 ontologies (including 131 OBO Foundry Library ontologies) with over four million terms. Ontobee provides a user-friendly web interface for querying and visualizing the details and hierarchy of a specific ontology term. Using the eXtensible Stylesheet Language Transformation (XSLT) technology, Ontobee is able to dereference a single ontology term URI, and then output RDF/eXtensible Markup Language (XML) for computer processing or display the HTML information on a web browser for human users. Statistics and detailed information are generated and displayed for each ontology listed in Ontobee. In addition, a SPARQL web interface is provided for custom advanced SPARQL queries of one or multiple ontologies.

A key aim of systems biology is the reconstruction of molecular networks. We do not yet, however, have networks that integrate information from all datasets available for a particular clinical condition. This is in part due to the limited scalability, in terms of required computational time and power, of existing algorithms. Network reconstruction methods should also be scalable in the sense of allowing scientists from different backgrounds to efficiently integrate additional data. We present a network model of acute myeloid leukemia (AML). In the current version (AML 2.1), we have used gene expression data (both microarray and RNA-seq) from 5 different studies comprising a total of 771 AML samples and a protein-protein interactions dataset. Our scalable network reconstruction method is in part based on the well-known property of gene expression correlation among interacting molecules. The difficulty of distinguishing between direct and indirect interactions is addressed by optimizing the coefficient of variation of gene expression, using a validated gold-standard dataset of direct interactions. Computational time is much reduced compared to other network reconstruction methods. A key feature is the study of the reproducibility of interactions found in independent clinical datasets. An analysis of the most significant clusters, and of the network properties (intraset efficiency, degree, betweenness centrality, and PageRank) of common AML mutations demonstrated the biological significance of the network. A statistical analysis of the response of blast cells from 11 AML patients to a library of kinase inhibitors provided an experimental validation of the network. A combination of network and experimental data identified CDK1, CDK2, CDK4, and CDK6 and other kinases as potential therapeutic targets in AML.