The International Nucleotide Sequence
Database Collaboration
Guy Cochrane*, Ilene Karsch-Mizrachi and Yasukazu Nakamura on behalf of the
International Nucleotide Sequence Database Collaboration
EMBL – European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton,
Cambridge CB10 1SD, UK
Received October 23, 2010; Accepted October 25, 2010
ABSTRACT
Under the International Nucleotide Sequence
Database Collaboration (INSDC; http://www.insdc.
org), globally comprehensive public domain nu-
cleotide sequence is captured, preserved and
presented. The partners of this long-standing col-
laboration work closely together to provide data
formats and conventions that enable consistent
data submission to their databases and support
regular data exchange around the globe. Clearly
defined policy and governance in relation to free
access to data and relationships with journal pub-
lishers have positioned INSDC databases as a key
provider of the scientific record and a core founda-
tion for the global bioinformatics data infrastructure.
While growth in sequence data volumes comes no
longer as a surprise to INSDC partners, the uptake
of next-generation sequencing technology by main-
stream science that we have witnessed in recent
years brings a step-change to growth, necessarily
making a clear mark on INSDC strategy. In this
article, we introduce the INSDC, outline data
growth patterns and comment on the challenges
of increased growth.
INTRODUCTION
The International Nucleotide Sequence Database
Collaboration (INSDC; http://www.insdc.org) represents
one of the most celebrated global initiatives in public
domain data sharing. Growing from efforts in the early
1980s to capture and present the increasing volumes of
sequence and annotation that arose from the emerging
application of sequencing techniques, by 1987, the
INSDC had taken shape with the stable three party mem-
bership that persists to this day. The parties to the collab-
oration are the DNA Databank of Japan (DDBJ) at the
National Institute for Genetics in Mishima, Japan; the
European Molecular Biology Laboratory’s European
Bioinformatics Institute (EMBL-EBI) in Hinxton, UK;
and the National Center for Biotechnology Information
(NCBI) in Bethesda, Maryland, USA. Together, the
INSDC partners set out to provide a globally comprehen-
sive collection of public domain nucleotide sequence and
associated metadata. Coverage includes the spectrum of
data, ranging from raw reads, through assembly and
alignment information, to submitted functional annota-
tion of assembled sequences. Raw data archives under
the collaboration are known as the Trace Archive for
raw data from capillary electrophoresis platforms and
the Sequence Read Archive [SRA, (1)] for raw and
read alignment data from next-generation platforms.
Assembled sequences and annotations are available from
DDBJ (2), the EMBL-Bank component of the European
Nucleotide Archive (3) and GenBank from NCBI (4).
Routine data exchange, standard formats and, increasing-
ly, the sharing of technology, provide global synchrony
across the collaboration.
COLLABORATIVE INSTRUMENTS
The INSDC supports data exchange pipelines through the
development and maintenance of a number of core collab-
orative instruments. The oldest of these is the INSDC
Feature Table Document, in which functional annotation
conventions are described at both syntactic and semantic
levels. Typically updated twice a year, the most recent
version is available at: http://www.insdc.org/documents/
feature_table.html. Over time, this specification has
defined a bioinformatics standard used well beyond the
INSDC both at the level of a format for data presentation,
exchange and input for analysis tools and as a starting
point for the development of annotation systems and
technologies based on the feature key and qualifier
definitions.
A second key collaborative instrument is the unified
accessioning system. Through the sharing of the accession
namespace, INSDC accessions are universal across the
*To whom correspondence should be addressed. Tel: +44 1223 492 564; Fax: +44 1223 494 468; Email: cochrane@ebi.ac.uk
Published online 23 November 2010 Nucleic Acids Research, 2011, Vol. 39, Database issue D15–D18
doi:10.1093/nar/gkq1150
� The Author(s) 2010. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/
by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
collaborators’ services such that a single accession will
return the same sequence regardless of the query site.
A third core collaborative instrument is the data model
that underlies the SRA (1). In the SRA, metadata, with
information relating to a sample, experimental design,
library creation and machine configuration, are expressed
and exchanged in a series of XML documents. The
sequence read, quality and read alignment data are
stored in binary data files and linked to the SRA
metadata layer.
A further collaborative instrument of importance is the
INSDC status convention (http://www.insdc.org/insdc_
status.html), in which a consistent level of availability
for given records is maintained across the INSDC
partners. This system supports such concepts as fully
public data, data held confidential prior to publication
and data suppressed as updated improved data become
available.
Finally, during 2010, significant effort has been invested
in a further collaborative instrument, the developing
BioProjects database, in which data providers and
INSDC database curators collate top-level information
that relates otherwise dispersed sequence records to
coherent studies that target complete genomes, transcrip-
tomes, metagenomics projects, targeted locus studies and
many more. While INSDC partners have collected infor-
mation under this initiatiave, a major new schema expected
in 2011 will support data access and mining tools.
POLICY
INSDC partners operate coordinated and integrated
services closely. For the data submitter, it is only necessary
to provide sequence data to one of the partners. Sequences
are accessioned across a single namespace such that an
accession search yields the same data content regardless
of which partner institute has provided the search facility.
In order to satisfy local requirements and to offer optimal
integration with partner institute resources beyond
INSDC, submission and presentation tools are developed
and maintained independently at the partner institutes.
These tools are available at: http://www.ddbj.nig.ac.jp/,
http://www.ebi.ac.uk/ena/ and http://www.ncbi.nlm.nih.
gov/ for DDBJ, ENA and NCBI, respectively, and
linked from http://www.insdc.org/.
Clear principles on data ownership have been developed
by the INSDC databases. Importantly, INSDC databases
are data hosts and not owners; while there are certain
syntactic and semantic compliance validations for
incoming data, data ownership, and hence editorial
control of the scientific content, remains with the
original data provider. Furthermore, only data owners
and their approved delegates are permitted to update
their records. Data submitted to one of the partners
undergo updates that are mediated by the recipient
INSDC institute; i.e. the recipient institute takes perman-
ent responsibility for the interaction between the submitter
and the INSDC over any given record or set of records.
Clearly, while such a system brings impartiality, it also
leaves scientific quality control at the hands of data
providers who, on occasion, are unable to support
ongoing updates to their records over extended periods,
typically as a result of a change in the focus of the sub-
mitter’s laboratory or as a result of employees leaving the
domain of research in question. As a primary archive, it is
important that INSDC places as few barriers to data pro-
viders as possible in order that their data and interpret-
ations are fully disseminated as part of the scientific
record. For this reason, INSDC content spans many
levels of completeness, thoroughness and, ultimately, reli-
ability as a feed of information into an analysis.
Recognizing this issue, it is the policy of the INSDC data-
bases to strive for systems under which quality, complete-
ness and thoroughness can be evaluated and expressed to
allow users to make best judgements on confidence in dif-
ferent INSDC records under different analyses.
While it is mainstream dogma in bioinformatics that any
paper in which new sequence is described cites INSDC
accession numbers that are associated with sequences
that have been submitted by the authors of the paper,
this ‘mandatory submission’ concept arose not passively,
but through the efforts of INSDC member institutions and
other proponents of open data sharing. As an example of
good practice in public data dissemination, INSDC
partners acknowledge the ongoing support of the publish-
ers of major life science journals in this endeavour.
INSDC data are provided openly and free of charge to
users. While many records are made publicly available
immediately following submission, those kept confidential
prior to publication are released publicly as soon as the
work is presented in a publication. It is necessary, in order
to comply with the consent agreements of human donors
who have provided material for sequencing, to require
authorization over access to some records; INSDC insti-
tutes work under their respective legislative systems with
the appropriate ethical bodies and committees to achieve
appropriate levels of security.
The INSDC has a long established International
Advisory Committee that is charged with providing
INSDC with scientific and strategic advice on develop-
ment and policy issues (see http://www.insdc.org/
advisors.html). The senior scientists who make up the
committee also play an important role as advocates for
the INSDC [(5) and http://www.insdc.org/documents/
open_letter.txt].
CONTENT IN 2010
In 2010, INSDC databases have grown overall around
3-fold in terms of the number of bases (Figure 1).
Behind this absolute growth are increases in the
numbers of assembled sequences of 19% (from 164 to
195-million sequences) and a greater than two-fold
increase in the number of next-generation-based experi-
ments in SRA (from around 13 000 to 31 000). While it
is not surprising that raw next-generation sequencing data
contributes the greatest component of data growth in
INSDC databases, a slight but persistent pattern of
falling rate of accumulation of assembled sequences is
evident. While the causes of this are unclear, amongst
D16 Nucleic Acids Research, 2011, Vol. 39, Database issue
the many possible explanations are the trend towards less
complete (in traditional terms) genome sequencing, and
hence a lower likelihood of a need of data generators to
present conventional assembled sequence and functional
annotation to the public; indeed it is clear from a break-
down of assembled sequence base contributions (Figure
1b) that assembled sequence records from whole genome
shotgun studies now contribute an increasingly significant
component of assembled sequences overall. Further ex-
planations, perhaps, include the saturation of sequencing
capacity by next-generation sequencing machines whose
outputs remain to date, in comparison with those of ca-
pillary electrophoresis platforms, less amenable to
sequence assembly methods.
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
(Figure 2). Furthermore, while the taxonomic diversity
of complete genomes has grown with increasing rate
over time, it is clear that overall taxonomic coverage,
albeit for many taxa with very sparse sequence represen-
tation, has also undergone increasing growth over time
(Figure 3).
FUTURE CHALLENGES
Throughout the history of nucleic acid sequencing, experi-
mentalists and data resource providers have become ac-
customed to exponential growth in data (Figure 1),
resulting from both increased automation and broadening
adoption of molecular methods into the mainstream life
sciences. While this traditional exponential growth has
created challenges at technical, social and economic
levels, the recent technology shift into ‘next-generation’
sequencing platforms has brought a step-change to the
nature of growth, which provides perhaps the greatest
challenge to date for INSDC partners.
Next-generation technologies bring new technical chal-
lenges. Leverage of recent advances in micro-fluidics and
imaging technology provide the current next-generation
platforms, namely Roche/454, Illumina and Life
Technologies/SOLiD, with the capacity to yield greatly
increased numbers of parallel reads from clonally
amplified single molecules. So-called ‘next next-
generation’ platforms promise to bring this level of
parallel output to direct single molecule sequencing
through the use of advanced imaging and other sensor
technologies. While the level of parallel output brings in
itself an impressive step-change in data volumes, it is the
unprecedented growth in throughput that we have seen to
date that is perhaps more challenging. In extreme cases,
we have witnessed aggressive technology improvements
for a next-generation platform with yield doubling
time of as little as 5 months. When contrasted with the
historical doubling time for, say, disk density per unit cost,
of �18 months, it is clear that simply containing
Figure 1. (a) Base pairs in INSDC over time, excluding the Trace
Archive (raw data from capillary sequencing platforms). Cumulative
data volume in base pairs over time. (b) Base pairs in INSDC over
time since 2002, 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.
Figure 2. Growth in complete genomes. The layered chart shows
the number of complete genomes available from INSDC databases
over time. The end of 2010 time point is conservatively (linearly)
extrapolated from October 2010 figures, which are the latest available
at the time of submission.
Figure 3. Taxonomic coverage. Growth in the number of taxa with
associated sequence (or with subordinate taxa with associated sequence)
over time.
Nucleic Acids Research, 2011, Vol. 39, Database issue D17
next-generation data in affordable storage media, under a
sustainable economic model, is a key technical challenge.
As stakeholders, the INSDC partners are contributing to
and engaging with local and community efforts to develop
data reduction, compression and other methodologies to
rise to the challenge of aggressive sequencing technology
growth. One part of this activity drives algorithmic devel-
opment and method optimization, while another asks
critical questions as to the value of the different data com-
ponents that we preserve within our archives.
The advent of next-generation sequencing technology
brings a further challenge, for which likely solutions will
come less from cutting-edge technical developments, but
rather from social and organizational innovation. The
enormous reduction in cost has driven a broad uptake
of sequencing across a huge breadth of applications well
beyond traditional genome and transcriptome sequencing
for the purposes of functional annotation. Through the
availability of new approaches such as next-generation
sequence-based epigenomics, resequencing, metatranscrip-
tomics and quantitative expression, sequencing has now
become a staple general assay platform for the life scien-
tist. Furthermore, in many cases, it is no longer necessary
even for the user to understand fully the intricacies of the
sequencing-based components of their work. How, then,
can the INSDC continue to serve best such a broadening
user base? Developing expertise in all new sequencing
related applications within INSDC through training and
new recruitment is unlikely to be sustainable. The strategy
adopted by INSDC has been the establishment of close
collaborations with groups having specialized expertise,
such as GEO (6) and ArrayExpress (7) for functional
genomics experiments. Increasingly in these arrangements,
access to INSDC data is provided through these
collaborating groups which are better placed for providing
specialized data submission, presentation and integration
tools. In a further example, work with the Consortium for
the Barcoding of Life and the Genomics Standards
Consortium has led to an INSDC-provided keyword
applied to those records that reach compliance with
such standards as the barcode data standard and the
community-developed Minimal Information about a
Genome Sequence (MIGS) standard [http://www
.barcoding.si.edu/PDF/DWG_data_standards-Final.pdf,
(8)]. This model is sustainable not only because it appor-
tions work appropriately (generic bioinformatics and
data infrastructure work goes to INSDC and work in
specialist biological domains goes only to the appropriate
experts), but also because it apportions responsibility for
justification to funders and compliance with governance
protocols to those most equipped for these tasks—the
experts in the domain.
FUNDING
EBI by the European Molecular Biology Laboratory; the
European Commission; Wellcome Trust, at DDBJ by the
Ministry of Education, Culture, Sports, Science and
Technology of Japan; at the NCBI by the Intramural
Research Program of the National Institutes of Health;
National Library of Medicine. Funding for open access
charge: European Molecular Biology Laboratory.
Conflict of interest statement. None declared.
REFERENCES
1. Leinonen,R., Sugawara,H. and Shumway,M., on behalf of the
International Nucleotide Sequence Database Collaboration (2011)
The Sequence Read Archive. Nucleic Acids Res., 39, D19–D21.
2. Kaminuma,E., Mashima,J., Kodama,Y., Gojobori,T.,
Ogasawara,O., Okubo,K., Takagi,T. and Nakamura,Y. (2010)
DDBJ launches a new archive database with analytical tools
for next-generation sequence data. Nucleic Acids Res., 38,
D33–D38.
3. Leinonen,R., Birney,E., Bower,L., Cerdeno-Ta´rraga,A., Cheng,Y.,
Cleland,I., Faruque,N., Goodgame,N., Gibson,R., Jang,M. et al.
(2011) The European Nucleotide Archive. Nucleic Acids Res., 39,
D28–D31.
4. Benson,D.A., Karsch-Mizrachi,I., Lipman,D.J., Ostell,J. and
Sayers,E.W. (2010) GenBank. Nucleic Acids Res., 38, D46–D51.
5. Brunak,S., Danchin,A., Hattori,M., Nakamura,H., Shinozaki,K.,
Matise,T. and Preuss,D. (2002) Nucleotide Sequence Database
Policies. Science, 298, 1333.
6. Barrett,T., Troup,D.B., Wilhite,S.E., Ledoux,P., Rudnev,D.,
Evangelista,C., Kim,I.F., Soboleva,A., Tomashevsky,M.,
Marshall,K.A. et al. (2009) NCBI GEO: archive for
high-throughput functional genomic data. Nucleic Acids Res., 37,
D885–D890.
7. Parkinson,H., Kapushesky,M., Kolesnikov,N., Rustici,G.,
Shojatalab,M., Abeygunawardena,N., Berube,H., Dylag,M.,
Emam,I., Farne,A. et al. (2009) ArrayExpress update–from an
archive of functional genomics experiments to the atlas of gene
expression. Nucleic Acids Res., 37(Suppl. 1), D868–D872.
8. Field,D., Garrity,G., Gray,T., Morrison,N., Selengut,J., Sterk,P.,
Tatusova,T., Thomson,N., Allen,M.J., Angiuoli,S.V. et al. (2008)
The minimum information about a genome sequence (MIGS)
specification. Nature Biotechnol., 26, 541–547.
D18 Nucleic Acids Research, 2011, Vol. 39, Database issue
