The International Nucleotide Sequence Database Collaboration.

The International Nucleotide Sequence
Database Collaboration
Ilene Karsch-Mizrachi1,*, Yasukazu Nakamura2 and Guy Cochrane3, on behalf of the
International Nucleotide Sequence Database Collaboration
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health,
45 Center Drive, Bethesda, MD 20892, USA, 2Center for Information Biology and DNA Data Bank of Japan,
National Institute of Genetics, Research Organization for Information and Systems, Yata, Mishima 411-8510,
Japan and 3EMBL – European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton,
Cambridge CB10 1SD, UK
Received October 18, 2011; Accepted October 19, 2011
ABSTRACT
The members of the International Nucleotide
Sequence Database Collaboration (INSDC; http://
www.insdc.org) set out to capture, preserve and
present globally comprehensive public domain nu-
cleotide sequence information. The work of the
long-standing collaboration includes the provision of
data formats, annotation conventions and routine
global data exchange. Among the many develop-
ments to INSDC resources in 2011 are the newly
launched BioProject database and improved handl-
ing of assembly information. In this article, we
outline INSDC services and update the reader on
developments in 2011.
INTRODUCTION
With the arrival of 2012, the International Nucleotide
Sequence Database Collaboration (INSDC; http://www
.insdc.org) enters its third decade of existence. This fun-
damental global data exchange collaboration serves as a
model for data sharing across and beyond the life sciences.
Together, the three INSDC partners, the DNA Databank
of Japan (DDBJ; http://www.ddbj.nig.ac.jp/) at the
National Institute for Genetics in Mishima, Japan; the
European Molecular Biology Laboratory’s European
Bioinformatics Institute (EMBL-EBI; http://www.ebi.ac.
uk/ena) in Hinxton, UK; and the National Center for
Biotechnology Information (NCBI; http://www.ncbi.nlm
.nih.gov/genbank/) in Bethesda, Maryland, USA,
capture, preserve and present the permanent scientific
record for nucleic acid sequencing and associated infor-
mation. Over the years of collaboration, the scope of
sequencing activity has grown enormously and INSDC
has developed a mandate that covers the richness of the
domain, including repositories and services for raw data
(the global Trace Archives and Sequence Read Archive
[SRA, (1)], assembly data, experimental design details,
taxonomic information, functional annotation and large
sequencing project information.
The smooth operation of the INSDC depends on the
existence and maintenance of a number of collaborative
instruments and policies that are documented on the
INSDC website. These include the Feature Table
Definitions and Status Definition documents, the global
accessioning system, rapid data exchange between partners
and core INSDC policies, such as support for mandatory
data submission in support of literature publication, de-
veloped in collaboration with the INSDC International
Advisory Committee. Further details of collaborative in-
struments and policies have been presented (2).
In this article, we outline the recent developments and
report in detail on two major areas of development, the
launch of the BioProject database and improvements to
handling of assembly information, that allow INSDC
partners to respond to changing user needs. Finally, we
provide an update on INSDC content in 2011.
RECENT DEVELOPMENTS
Members of the INSDC meet annually to discuss issues
related to maintaining the sequence archives. These issues
range from the addition of feature or qualifier elements to
the feature tables present in the Flat File report format in
the traditional archive records to policy issues and
strategies for dealing with the increasing sequence data
to be archived. In 2011, the annual meeting was held in
Osaka, Japan. At the meeting, we finalized a number
of important changes to the document describing the
availability of sequences across INSDC partner sites
(http://www.insdc.org/documents/status_document.html).
*To whom correspondence should be addressed. Tel: +301 435 5929; Fax: +301 480 2918; Email: mizrachi@ncbi.nlm.nih.gov
Published online 12 November 2011 Nucleic Acids Research, 2012, Vol. 40, Database issue D33–D37
doi:10.1093/nar/gkr1006
Published by Oxford University Press 2011.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This document describes such concepts as fully public
data, data held confidential prior to publication and
data replaced as updated improved data become available.
It also defines instances where sequences that were once
public may be removed.
A number of new feature keys and qualifiers were
adopted. Beyond those that relate to changes to the way
in which assembly information is handled (see below), the
new feature keys centromere and telomere were adopted
to support specific labeling of these subchromosomal
regions. In addition, changes in usage of /pseudo and
the introduction of /pseudogene were agreed. Details of
these updates are announced at INSDC partner sites
and are laid out, including dates and timelines for
implementation, in the October Feature Table
Definitions document (http://www.insdc.org/documents/
feature_table.html).
Discussion of SRA centered on schema simplifications,
data compression and preparation for sustainable mech-
anisms of data exchange. Details have been published in
this issue (1).
BIOPROJECT DATABASE
BioProject was released as a collaborative resource in
2011. It is becoming increasingly important to collect
metadata associated with large-scale sequencing initiatives
Figure 1. Sample BioProject records, shown from the NCBI website, for (A) a genome sequencing project and (B) an epigenomic project. Linkages
are created from the BioProject record to the resources containing data and from the BioProject record to other BioProject records that are part of
the same initiative or contain related data.
D34 Nucleic Acids Research, 2012, Vol. 40, Database issue

and for the archives to aggregate this information to allow
users to easily access the information. For the past few
years, genome sequence submissions to INSDC contained
a Genome Project identifier with links to the Genome
Project database. The Genome Project record held infor-
mation about genomic molecules for the sequencing effort
of a particular species with links to the INSDC accessions.
It became increasingly clear that accessions from other
types of initiatives needed to be aggregated and cited in
a central database. This is especially true when there are
disparate types of data in a single funded initiative. The
new BioProject database (3), which has superseded
Genome Project, enables submitters to describe initiatives
that include data from transcriptome, metagenome,
targeted locus and multi-isolate studies that initiate from
a single organization, consortium or funding initiative.
Additionally, linkages can be created between different
project types to provide users with a single entry point
to the data. Linkages may also be established between
initiatives with data deposited in the INSDC sequence
archives and repositories that house analysis of raw
sequence output, such as GEO (4), ArrayExpress (5) and
dbGaP. Sample BioProject records with links to different
data types are shown in Figure 1.
HANDLING OF ASSEMBLY INFORMATION
In 2008, an agreement was reached by the major genome
browser and annotation groups, Ensembl, NCBI and
UCSC, whereby each site would be required to consist-
ently display the same assemblies with the same coordin-
ate systems (http://www.ensembl.org/info/about/legal/
browser_agreement.html). The group agreed that:
(i) data displayed in the assembly should be displayed only
after it has been released in INSDC. (ii) The sequence
identifiers used in the browser and publicly distributed
via FTP should be correlated with the INSDC records.
(iii) All browsers will refer to any given assembly by the
same name, preferably a submitter approved name. Prior
to this agreement, in many instances, the browsers were
annotating and displaying different versions of genome
assemblies which made it difficult to compare data ori-
ginating from different data providers. In light of this,
INSDC must work with the genome centers producing the
data to ensure genomes are submitted and released in a
timely manner so that they may be available for use by the
browsers.
In the genomics community, the format of submission
and exchange for genome assembly data is the AGP
(http://www.ncbi.nlm.nih.gov/projects/genome/assembly/
agp/AGP_Specification.shtml). This tabular format de-
scribes the assembly of a genomic object, i.e. scaffold
and/or chromosome, from component sequence records.
Each row of the AGP describes a piece of the object and
information about the coordinates, type of component or
gap and linkages are specified in the columns. At INSDC,
the constructions delineated in the AGP file are built as
CON Flat File records, which contain instructions for
how to build a scaffolded sequence from the component
sequence records.
The AGP specification captures richer information
about the type of gap, but this has to-date been discarded
in the INSDC Flat File view of the CON record.
Additionally, the AGP specification will be extended to
explicitly indicate the evidence for linkage between two
components. This information would also be potentially
lost in the CON representation of the sequence assembly.
Therefore, to better capture this information, INSDC will
improve the format and display of the CON record by
introducing a new feature key, assembly_gap and two
new qualifiers, /gap_type and /linkage_evidence to
capture the additional information that is included in
AGP files that was previously lost from the INSDC
records. This change will also enable genome centers and
the browser groups to interconvert losslessly the INSDC
CON representation and the AGP files.
CONTENT IN 2011
In 2011, INSDC databases have grown overall around
2-fold in terms of the number of bases (Figure 2a).
Behind this absolute growth are increases in the
numbers of assembled sequences of 14% (Figure 3). The
rate of accumulation of assembled sequences is decreasing
over time as the rate of accumulation of SRA bases in-
creases. This is evident especially for bulk data sequence
Figure 2. (A) Cumulative base pairs in INSDC over time, excluding
the Trace Archive (raw data from capillary sequencing platforms).
(B) Base pairs in INSDC over time since 1980, broken down into
selected data components. Cumulative data volume in base pairs
broken down into assembled sequence (whole genome shotgun
methods and others) and raw next-generation-sequence data.
Nucleic Acids Research, 2012, Vol. 40, Database issue D35

data submissions, such as Expressed Sequence Tags (EST)
and Genome Survey Sequences (GSS) where the SRA de-
position is more appropriate. To a lesser extent, Whole
Genome Shotgun (WGS) is also being deposited at a
slower rate than previously even though the contribution
of WGS sequences is still a significant (Figures 2b and 3)
component of traditional sequences.
Despite this slowing of growth in assembled sequence
submissions to INSDC databases, it is clear that the cata-
logue of public domain genomes continues to grow rapidly
and is expected to continue to grow as the availability and
quality of next-generation sequence is enhanced. In the
first 9 months of 2011, over 1200 new genomes were de-
posited, more than half of these were genomes from
species that were not previously sequenced. Figure 4
shows the growth in the number of new species with
genomes deposited in INSDC. We anticipate at least a
10-fold increase in the number of genomes submitted to
INSDC in the next 2 years.
FUNDING
NCBI by the Intramural Research Program of the
National Institutes of Health; National Library of
Medicine; European Nucleotide Archive by the
European Molecular Biology Laboratory, the Wellcome
Trust, the FP7 Programme of the European Commission
and the Biotechnology and Biological Sciences Research
Council; at DDBJ by the Ministry of Education, Culture,
Sports, Science and Technology of Japan. Funding for
Figure 3. Cumulative growth in the number of sequences included in the traditional INSDC sequence archives over time. Bulk sequence data
includes non-WGS bulk submission types i.e. EST, GSS, Patent and Transcriptome Shotgun Assembly (TSA). WGS includes the number of sequence
overlap contigs. Non-bulk data is the remainder.
Figure 4. Growth in genomes. The layered chart shows the number of
new species with genomes entered into INSDC databases over time by
taxonomic group. The 2011 time point includes data released in the first
9 months.
D36 Nucleic Acids Research, 2012, Vol. 40, Database issue

open access charge: the Intramural Research Program of
the National Institutes of Health, National Library of
Medicine.
Conflict of interest statement. None declared.
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