The miRBase database – an essential resource for tool development and pharmaceutical research
Submitting InstitutionUniversity of Manchester
Unit of AssessmentBiological Sciences
Summary Impact TypeTechnological
Research Subject Area(s)
Mathematical Sciences: Statistics
Biological Sciences: Genetics
Information and Computing Sciences: Information Systems
Summary of the impact
MicroRNAs are a class of non-protein-coding RNA genes that regulate the
expression of protein-coding
mRNAs in animals and plants. Researchers at the University of Manchester
developed a microRNA database (miRBase) which has become an essential
researchers both in academia and the pharmaceutical industry. The database
is the central global
repository for all published microRNA sequences and annotation.
miRBase data enables production of novel experimental kits and resources
qPCR assays and microarrays) by companies including ABI, Invitrogen,
Sigma-Aldrich and Exiqon.
Tools produced by these companies underpin experimental microRNA research
and industrial settings, which benefit product development, drug discovery
and clinical research.
Exiqon reported more than 110 million DKK in revenue from their life
science business in 2012,
with main product lines involving microRNAs.
Griffiths-Jones originally created miRBase at the Wellcome Trust Sanger
Institute, with the first
major publication in 2004. The impact is based on the continued
development and improvement of
the database carried out in the Griffiths-Jones research group at the UoM
from 2007 onwards.
The key researchers involved in the development of the miRBase database
at the UoM are:
Dr Sam Griffiths-Jones (Senior Lecturer, 2007 to date)
Dr Antonio Marco, (Post-Doctoral Research Associate, 2008 to 2013)
Dr Ana Kozomara (Post-Doctoral Research Associate, 2009 to date)
The key research that underpins the development of the miRBase database
at the UoM is as
- The Griffiths-Jones group developed methods and pipelines to determine
functional relationships between microRNA gene sequences submitted to
the database by
microRNA researchers. miRBase is responsible for all microRNA gene
published literature. The group have assigned gene names for over 8000
provided by 300 researchers since 2008.
- They developed web tools and interfaces to facilitate access to
microRNA sequences and
annotation. These include methods for discovering microRNAs from deep
sequencing data ,
novel views of the data , and procedures to allow the user community
annotation, for example through a collaboration with the Wikipedia
online encyclopaedia which
began in 2012.
- The Griffiths-Jones group provided access to the primary underlying
evidence for every
microRNA gene annotation. They obtained and mapped over 300 third party
datasets and developed methods to query the microRNA dataset based on
expression, experiment, author etc. .
- The group also curate and provide links to other microRNA tools and
resources, including those
that predict functional targets of microRNAs and roles in disease.
miRBase is the sole authoritative source of all published microRNA
sequences. All microRNA
resources, including other microRNA databases and companies that produce
resources source microRNA sequence data directly or indirectly from
miRBase. The primary
impact derives from the development and improvement of the database. The
research group also contributes content to the database from in-house
novel microRNA discovery
References to the research
The research that led to the development of the miRBase database has been
published in high
impact journals and is highly cited. The Nucleic Acids Research papers
describing the database
[including 2, 4] have over 4800 Scopus citations including over 4200 since
1. Marco, A., Griffiths-Jones, S. (2012). Detection of microRNAs
in color-space. Bioinformatics.
28 (3). p.318-323. DOI:10.1093/bioinformatics/btr686.
3. Marco, A., Hui, J.H., Ronshaugen, M., Griffiths-Jones, S.
(2010). Functional shifts in insect
microRNA evolution. Genome Biol Evol. 2. p. 686-696.
Details of the impact
MicroRNAs are ~22 nucleotide non-protein-coding genes found in all animals
and plants. They
were discovered as a class in 2001. MicroRNAs act by binding to mRNA
transcripts to trigger their
down-regulation. They represent arguably the most widespread and important
mechanism of post-transcriptional
gene regulation. The human genome has over 1500 annotated microRNA genes
and it is predicted that over half of all human genes are regulated by
microRNAs. The microRNA
field is a rapidly expanding one; more than 75% of the data has been
deposited and curated since
2008. Commercial organisations, including large pharmaceutical companies,
have been quick to
adopt microRNA research programmes.
miRBase is the primary source of microRNA sequence data. All microRNA
research globally is
therefore impacted by the production, development and availability of
Pathways to impact
miRBase was created by Griffiths-Jones and was initially hosted and
supported by the Wellcome
Trust Sanger Institute. UoM hosts and maintains the miRBase from 2007 to
Reach and significance of the impact
The primary use of miRBase data is via the website and by bulk data
download from the FTP site.
Since 2008 the miRBase website has consistently received 40,000-50,000
visits per month from
20,000-30,000 unique users viewing 120,000-150,000 pages. Empirical data
shows that ~10% of
email queries are from commercial users. The miRBase database development
and use is
described in a series of publications from 2004 to date. In total, these
manuscripts have been cited
over 4200 times since 2008. Of these citing journal articles, 10% (424)
organisations as author affiliations (according to Scopus).
Derived commercial and monetary benefits:
The impact on the pharmaceutical industry of miRBase has been
considerable. It has allowed new
products and significant research gains to be made every year since 2008.
A number of companies, such as Exiqon [A], LC Sciences [B], Comprehensive
(formerly Febit) [C], Agilent [D], Sigma-Aldrich [E], ABI, Exiqon,
GenoSensor, Invitrogen and many
others, make microRNA microarrays and other experimental resources from
sourced from miRBase. For example, Exiqon sell 20 different products that
rely on data from
miRBase, including qPCR assays and LNA microarray technologies for
These products are built using miRBase sequence data, and are the most
significant contributor to
Exiqon's life science business which reported more than 110 million DKK in
revenue in 2012 [F].
The Vice President for Research and Development at Exiqon stated: "From
interaction with our
customers we understand that everyone in the miRNA research community
consider the miRNA
content of miRBase to represent the golden standard miRNA repository.
Over the years, Exiqon
has used miRBase as a reference for further development of new products
and updating of
existing products. Coverage of miRNAs in a given miRBase version has
always been a central part
of the product information accompanying products in the different
portfolios like the miRCURY
ABI manufacture and sell Taqman microRNA PCR assays at an off-the-shelf
cost of around £250
for sequences that are in miRBase, and custom-designed for around £400 for
those which are not.
Other companies follow a similar model. These commercial tools produced by
third parties from
miRBase data underpin experimental studies of microRNA genes in academic
and industry labs,
and curation of microRNA sequences lowers the cost of experimental assays
for the user.
Companies aim to update their products as quickly as possible after a
release of a new miRBase
version; the schedule of production and sales of these companies is
therefore partly governed by
miRBase updates. For example, Exiqon "plan timely product updates and
developments taking the update and release of new miRBase versions into
MicroRNAs have been implicated in a wide range of disease processes and
have been shown to
act as biomarkers for cancer types, stages, disease prognosis and drug
Pharmaceutical companies, including AstraZeneca and GlaxoSmithKline, have
streams investigating the use of microRNAs as biomarkers. For example,
AstraZeneca has a
number of lines of research into the roles and pharmaceutical relevance of
microRNAs in oncology.
A 200er Ase200et s Acr200ercA sArs200ees200eirseec ce200erses r200esnes: "we
use miRBase microRNA sequences to
design primers for PCR in order to validate specific microRNAs as
potential biomarkers. We also
explore links from miRBase to up-to-date predicted and validated
microRNA target sites, in order to
identify pathways and functions" [G].
Drugs that target microRNAs are also showing clinical promise. For
Therapeutics Inc. is a biopharmaceutical company dedicated to developing
therapies that target
microRNA in disease areas of high unmet medical need. Drugs for chronic
heart failure (mir-208),
post-myocardial infarction remodelling (mir-15/195) and cardiometabolic
disease (mir-378) are in
the pre-clinical phase [H].
Santaris Pharma also has a phase IIa clinical trial drug (miravirsen)
that acts by inhibiting miR-122.
The Associate Director states that: "Santaris has so far conducted drug
discovery projects to find
drug candidates against > 30 specific microRNAs. In all cases these
projects started from the
sequence of the target microRNA as annotated in miRBase" [I].
Miravirsen is the first microRNA therapy for hepatitis C. At the 2012
International Liver Congress, a
renowned professor from the Department of Gastroenterology and Hepatology,
of Amsterdam, stated in a press release issued by Santaris: "Due to
its ability in targeting miR-122,
miravirsen has the potential to change the way hepatitis C is treated."
Further trials are planned to test miravirsen in people with all HCV
genotypes, using longer
durations, and in combination with direct-acting antivirals. The success
of these and newly
emerging programmes and the downstream benefits to health are dependent on
the availability of
miRBase is held as the official arbiter of microRNA gene status and
annotation by the following
bodies: the human (HUGO/HGNC) and mouse (MGI) gene nomenclature
committees, RefSeq at
the National Center for Biotechnology Information (NCBI) and the
International Union of Basic and
Clinical Pharmacology (NC-IUPHAR). miRBase datasets are also distributed
by the NCBI, the
University of California, Santa Cruz and Ensembl genome browsers. These
resources and bodies
have their own substantial user bases which are also significantly
impacted by miRBase work.
Sources to corroborate the impact
Example press releases and products from companies that make microRNA
Exiqon use miRBase v16
data to produce microRNA microarrays
use miRBase v17 data to produce microRNA microarrays
Comprehensive Biomarker Centre (formerly Febit) use miRBase v16 and V17
Agilent use miRBase v16 data to produce human microRNA
Sigma Life Sciences use miRBase V17 data to produce microRNA mimics
Corroborating letters and sources:
F. Letter from Vice President for Research and Development, Exiqon,
range of products that rely on miRBase data.
G. Letter from Oncology Bioinformatics group, AstraZeneca. Describes
use of miRBase sequence
data in screens for cancer biomarkers.
miragen website showing pipeline of drug
discovery using microRNA sequences.
I. Letter from Santaris Pharma. Corroborates how the miRBase has
played a role in developing
the miR-122 inhibitor, miravirsen.