aspects generally appears on the experimental data records. BioSample attributes are captured as structured name: value pairs, for example, tissue: liver or lat_lon: 39.0, 77.1. The database supports and encourages use of dictionaries of attribute names and synonyms but can also accept any custom attributes that the submitter chooses to provide. While controlled vocabularies are sup- ported for attribute ﬁeld names, formal ontologies for at- tribute values are not currently supported. Speciﬁc attribute name dictionaries may be utilized for speciﬁc sample types. Thus, in the Submission Portal, when a submitter speciﬁes what type of sample they have, the corresponding diction- ary is used to drive the request for appropriate attributes. Besides a general dictionary of common core attributes, the ﬁrst targeted dictionaries implemented in the NCBI BioSample database are the MiXS minimum information checklists for standardizing descriptions of genomes, metagenomes and targeted locus sequences as recently de- veloped by the Genomics Standards Consortium (13). These checklists comprise several packages in which relevant environmental and epidemiological data ﬁelds allow for a complete description of the samples being sequenced. The BioSample database is extendible in that dictionary terms and checklists can be added as new stand- ards develop. By guiding and encouraging submitters to use attribute dictionaries in this way, it can be expected that the descriptions for samples deposited via this route will converge and become more consistent over time. This move to broader standardization will in turn assist users to query across NCBI databases for data derived from samples that have speciﬁc attributes and values. BioSample relationships and linking The BioSample database supports capture of various types of relationships between samples. For example, for samples that represent cell lines derived from individuals with known family relations, pedigree information can be captured and used to group related samples together, facilitating linking to additional relevant records. In addition to these intra-database relationship links, inter-database links are employed to link samples to cor- responding experimental data within the primary data archives as well as to the BioProject(s) in which they participate. Reference BioSample records While many samples can be considered unique and are used only once, other samples, like commercial cell lines, are re-used over and over again by the research commu- nity. We are working with major cell line vendors, including ATCC and Coriell, to generate ofﬁcial represen- tations of commonly used and highly referenced samples. These are Reference BioSamples, so submitters who use these samples may bypass BioSample submission and simply reference relevant Reference BioSample records when depositing experimental data in any of NCBI’s primary data archives. Also, efforts will be made to map existing data sets from across NCBI archives to Reference BioSample records. Consequently, these records will serve Nucleic Acids Research, 2012, Vol. 40, Database issue D61 as hubs from which users can quickly locate a multitude of diverse data sets and projects derived from a given sample. Reference BioSample data will be exchanged and their accession numbers shared with our partners at the European Bioinformatics Institute (EBI) who are estab- lishing a similar BioSample database (14). All Reference BioSample data will be accessible from both the EBI and NCBI databases. Clinical samples The BioSample database does not support controlled access mechanisms and thus cannot host human clinical samples that may have associated privacy concerns. Rather, clinical samples will continue to be deposited in NCBI’s dbGaP database (8). The dbGaP and BioSample databases are collaborating to present sanitized versions of these data in BioSample, that is, versions where sensi- tive data attributes are omitted. This allows users to locate these data in BioSample, and then apply to dbGaP for access to the full descriptions as necessary. Current status At the time of writing, the BioSample database is populated with over 600 000 original submitter-supplied sample descriptions extracted directly from SRA, sanitized dbGaP samples, GenBank EST and GSS libraries and some GenBank MiXS-compliant samples. As such, while these records may be searched with keywords and attri- bute names to locate data of interest, it should be noted that these data are generally not curated and were submitted without guidance of the recently implemented BioSample dictionary attributes described above. Going forward, as usage of the NCBI Submission Portal and attribute dictionaries become more widespread, and as Reference BioSamples are loaded, sample descriptions should improve and become more consistent over time. DATABASE ORGANIZATION AND IMPLEMENTATION BioProject and BioSample data are stored in separate Microsoft SQL servers and encoded in XML. Databases are structured for efﬁcient storage, tracking and fast re- trieval. Figure 1 provides an overview and description of how BioProject, BioSample and experimental data objects may be organized and linked to each other. All BioProject and BioSample metadata are indexed into NCBI’s Entrez search and retrieval system. SUBMISSION PORTAL The BioProject and BioSample databases provide the in- frastructure in which to capture well-annotated, structured metadata that give context to the underlying data, but ultimately it is the researchers who are respon- sible for providing this information. Thus, it is essential to provide an effective mechanism by which data may be deposited. The NCBI Submission Portal, available at http://submit.ncbi.nlm.nih.gov, is being developed to guide submitters into supplying quality metadata via