D950 Nucleic Acids Research, 2012, Vol. 40, Database issue compounds into chemically related groups, the Bemis and Murcko (17) frameworks are calculated for all compounds. Publicly available gene expression data are currently obtained from NCI-60 DTP Human Tumour Cell Line Screen (18), The Cancer Genome Atlas (TCGA) and ArrayExpress (19). While the NCI-60 and TCGA data has been processed and integrated into canSAR the ArrayExpress data are obtained live via web services. Further annotation for cell lines and gene expression microarray probes is obtained and integrated from COSMIC (20), ATCC and speciﬁc platform providers (Affymetrix and Agilent). Large volume data repositories for RNAi data are not commonplace; hence, most of the RNAi data in canSAR are extracted manually from choice publications and web resources [e.g. (1,21,22,23)]. Increasingly, data is provided through sources such as the Broad Institute (http://www .broadinstitute.org//scientiﬁc-community/data) and such data will be added in the future from as many sources and collaborators as possible in order to bolster the con- ﬁdence in any ﬁndings. Gene copy number data have been obtained and integ- rated from the copy number variation (CNV) Project (24,25). Currently, this makes up 1.4 billion copy number data points for 747 cell lines. canSAR is useful because it brings together in one place all these diverse data. It is important at this point to remind readers that these data, as with any published data, are useful for hypothesis generation-speciﬁc measurements and endpoints need to be veriﬁed experimentally. To tackle the large variety of sources of protein inter- action data, we began by collaborating with two providers of compiled curated interaction data, namely STRING (26) and ROCK (27). Their APIs are utilized to obtain data while maintaining the beneﬁt of the efforts invested by these providers in annotation and conﬁdence curation. Future plans for canSAR include better utilization of PSICQUIC (28) and more extensive collaboration with resources such as IntAct (29) and Reactome (30). These data sources are all valuable sources of annotated protein– protein interactions. They have different strengths and focuses, e.g. STRING has a visually striking structural annotation paradigm, and IntAct and ROCK have exten- sive links for each node through their tabular representa- tions or though invoking options within Cytoscape. For detailed network analysis, such resources are very powerful. However, there is additionally a need to instantly annotate an interaction network by druggability, chemical screening, RNAi screening as well as structural annota- tion to highlight possible intervention points instantly. We aim to achieve this within canSAR (see case studies below) The primary source for canSAR structural data is the RCSB PDB (31). Data from PDBe (32) helps maintain an up-to-date mapping between various databases such as UniProt (8), Pfam(10) protein family repository, SCOP structure classiﬁcation database (33) and provides infor- mation in computationally parseable ﬁles. Ligand infor- mation is also gathered from PDBe in the form of PDBeChem. Domain speciﬁc information is gathered from SCOP and Astral (34). A number of structural descriptors are calculated for all structures using DSSP (35), Ligplot (36) and HBPlus (37), providing assignment of secondary structures, dihedral angles and interaction maps. The approved drugs from the FDA are captured (re- gardless of therapeutic indication) and their efﬁcacy targets were expert-curated from published literature (38). As well as providing this useful annotation, it is possible to infer druggability by precedence through the presentation of the sequence similarity to the existing targets of launched therapeutics (39). A continuing effort is being carried out by the canSAR team to manually curate cancer clinical candidates from clinical trial and company progress reports. Full up-to-date release notes are available on the canSAR interface. A snap shot of the release notes from August 2011 can be found in the Supplementary Data. Web visualization While canSAR integrates an unprecedented set of transla- tional research data, its major unique advantage is the presentation and interrogation tools. canSAR is available via http://cansar.icr.ac.uk. Users can obtain logical and concise summaries of broad state-of-the-art knowledge without being overwhelmed by pages of concatenated data. The interface provides biological annotation, gene expression, disease association, structural and pharma- cological data, and produces graphical and tabular summary reports pertaining to any aspect of these data. Additionally, wider ranging and more expert-style ques- tions can be asked of the data using the expert and batch query tools. The interface development is driven by typical use-cases in cancer translational research, drug discovery and chemical biology and caters for users from different backgrounds (biology, chemistry, clinical etc). Example entry points include target/cell line/compound keyword searches, sequence similarity searches, compound structure searches and the facility to upload lists of iden- tiﬁers as a query. Expert tools allow retrieval of extensive chemogenomic annotations, polypharmacology maps, compound selectivity and bioactivity proﬁles, expression details and pathway enrichment analysis. Almost all canSAR functionality is available without the need for registration. However, a simple user registration facility is available to enable running large batch searches (emails are sent when batch analysis is ready to view), saving favourite complex searches, data alerts or setting up regularly used ﬁlters etc. Data export and sharing Users often wish to export speciﬁc analysis results obtained from the interface. In most sections of canSAR, users are able to export the current results in various formats including Excel, tab-delimited text, SDF and MIABE (40) compliant XML. Detailed examples of the web interfaces usage can be found in the Case Studies section.