W610 Nucleic Acids Research, 2012, Vol. 40, Web Server issue or in JSON format. Database and RESTful web services have been designed and implemented to ensure high avail- ability of the servers and to be fast, what results in real-time queries most of the time. Our results provide a convenient solution to access and retrieve heterogeneous relevant biological information without the need of local databases installations. Data are always available by a high-availability cluster and queries have been tuned to ensure a real-time performance. BIOLOGICAL SOURCES CellBase database and web services have been designed to integrate and provide easy and efﬁcient access to the most relevant biological information. This access is provided through a comprehensive and extensible RESTful web services API. Currently, some of the model organisms supported are human, mouse, rat, zebraﬁsh, worm, fruit ﬂy, pig, dog and yeast (and soon new organisms will be added). CellBase integrates different data types from different sources into a relational database. These data comprise most relevant biological information taken from the main repositories. These data are organized in different sections depending on the type of information as described below. Core features We took genome sequences, genes, transcripts, exons, cytobands or cross references (xrefs) identiﬁers (IDs) from Ensembl (2). Protein information including se- quences, xrefs or protein features (natural variants, muta- genesis sites, post-translational modiﬁcations, etc.) were imported from UniProt (3). Regulatory CellBase imports miRNA from miRBase (4); curated and non-curated miRNA targets from miRecords (5), miRTarBase (6), TargetScan (7) and microRNA.org (8) and CpG islands and conserved regions from the UCSC database (9). Functional annotation OBO Foundry (1) develops many biomedical ontologies that are implemented in OBO format. We designed a SQL schema to store these OBO ontologies and >30 ontologies were imported. OBO ontology term annotations were taken from Ensembl (2). InterPro (10) annotations were also imported. Variation CellBase includes SNPs from dbSNP (11); SNP popula- tion frequencies from HapMap (12), 1000 genomes project (13) and Ensembl (2); phenotypically annotated SNPs were imported from NHRI GWAS Catalog (14), HGMD (15), Open Access GWAS Database (16), UniProt (3) and OMIM (17); mutations from COSMIC (18) and structural variations from Ensembl (2). Systems biology We also import systems biology information like interactome information from IntAct (19). Reactome (20) stores pathway and interaction information in BioPAX (21) format. BioPAX data exchange format enables the integration of diverse pathway resources. We successfully solved the problem of storing data released in BioPAX format into a SQL relational schema, which allowed us importing Reactome in CellBase. TECHNICAL DETAILS Architecture design and implementation CellBase database and web services architecture have been designed to be both very fast and fault-tolerant, thus providing a high-availability solution with no single point of failure. This is an important feature that makes CellBase very reliable and scalable if more servers are needed. Figure 1 shows a schema of the architecture. Some of the advantages of this architecture are that no installation of software tools or databases are needed by the user, as the whole API has been implemented using RESTful web services, and thus, database and web services API are always available. Data from different biological databases and sources were integrated into a normalized relational database, im- plemented in a MySQL replication cluster to support a high load access as shown in Figure 1. In total, >200 GB were stored in the database. To speed-up queries, indexes and summary tables were created, resulting in runtimes of a few milliseconds for most of the queries. In order to provide a high availability and load balancing to the MySQL replication cluster, a Keepalived (http:// www.keepalived.org) and HAProxy (http://haproxy.1wt .eu) services have been conﬁgured. Web services API have been designed and implemented using REST software architectural style. RESTful web services have some advantages over SOAP web services such as that they tend to be more lightweight, scalable and easy to build and consume, thus providing a fast access to data even in low bandwidth conditions. To achieve a higher performance, Java was chosen for the server implementation to both (i) connect to MySQL using JBoss Hibernate (http://www.hibernate.org) and (ii) to implement RESTful web services API using Jersey library (http://jersey.java.net). Apache Tomcat was chosen as Java application server to deploy the web archive (war ﬁle) with the RESTful web services API im- plementation. To provide a high availability and load balancing to these web services, a HAProxy (http:// haproxy.1wt.eu) was set up to balance Apache Tomcat instances. RESTful web services are registered in BioCatalogue (22) and access is free to all users. Servers CellBase MySQL replication cluster database is running in two high-end servers with two Intel Xeon Hexa-Core CPUs each, 96GB of memory and 6 SSD disks conﬁgured as a RAID-5 volume giving a 1,2TB of extremely fast