Annual Scientific Report 2015

Vertebrate Genomics Research
The most important result in our research into the
evolution of transcriptional regulation was a study
in collaboration with Duncan Odom’s group at the
University of Cambridge, jointly led by postdoctoral
fellow Camille Berthelot. We mapped and analysed the
evolution of genomic promoter and enhancer elements
across 20 mammalian species, including whale and
dolphin, to produce the most comprehensive view of
shared and lineage-specific promoter and enhancer
elements in the mammalian lineage. We found that
approximately half of all enhancers active in liver tissue
of any of our 20 assayed species are not found in any of
the other 19 species, but that these ‘recently evolved’
enhancers tend to be exacted from ancestral DNA
sequences shared across mammals. We also found that
approximately 16% of active liver promoters and 1% of
active liver enhancers are shared across the species, and
that promoters have certain evolutionary characteristics
similar to protein-coding genes.
We gained new insights into the role of cohesin in
genome regulation in the context of a collaboration
with the Merkenschlager group at Imperial College
London and with former PhD student Andre Faure,
now postdoctoral fellow at the CRG in Barcelona.
EMBO Postdoctoral Fellow Emily Wong contributed to
a study led by the Spector group at Cold Spring Harbor
Laboratory in the US, investigating chromatin changes
in response to a large genomic deletion.
Our research with the Spector group and the Marioni
group at EMBL-EBI showed that random monoallelic
gene expression, which refers to the transcription of
a gene from one of two homologous alleles, increases
upon embryonic stem-cell differentiation. These
results support a model in which random monoallelic
expression occurs stochastically during differentiation
and, for some genes, is compensated for by the cell
to maintain the required transcriptional output of
these genes.
Future plans
In 2016 we will continue to expand the functionality and
capacity of the Ensembl project, making our datasets
more useful and stable to support reproducible genome
interpretation. We will release new methods and tools
for scaling up to accommodate ever-larger datasets
and numbers of genomes. Using data from the Google
Analytics Event Tracking feature, we will improve the
Ensembl website experience for both first-time visitors
and experienced users. We will expand our outreach
and training, and continue to engage with researchers
on diverse online and in-person platforms. We will
grow and our major data resources, for example with
new human populations for the IGSR including those
Paul Flicek
Genes, Genomes and
Variation Resources
DSc Washington University, 2004. Honorary
Faculty Member, Wellcome Trust Sanger Institute
since 2008. At EMBL-EBI since 2005.
Team Leader at EMBL-EBI since 2007, Senior
Scientist since 2011.
from the Human Genome Diversity Project, new search
interfaces for HipSci and the first release of FAANG
data. In terms of GWAS, we will increase the depth
of gene-mapping information to all available genes
for each variant provided. To identify and display all
known variants in the GWAS catalog that co-segregate
with a variant of interest, we will integrate all linkage
disequilibrium information.
We will build on our studies of closely related mouse
species, continuing to investigate the function,
inheritance and evolution of the intensity of the
ChIP-seq signal (i.e. binding intensity). These
studies must be performed using a higher number of
experimental replicates than is standard to achieve an
effective analysis. We will investigate whether ChIP-seq
datasets could be used to uncover mitochondrial
heteroplasmy. We will work on a comparative
benchmark study between the primate and murine
clades, leveraging genomes from the Mus genus.
Selected publications
1000 Genomes Project Consortium et al. (2015) A global
reference for human genetic variation. Nature 526:68-74
Andersson L, et al. (2015) Coordinated international
action to accelerate genome-to-phenome with FAANG,
the Functional Annotation of Animal Genomes project.
Genome Biol. 16:57
Ing-Simmons E, et al. (2015) Spatial enhancer clustering
and regulation of enhancer-proximal genes by cohesin.
Genome Res. 25:504-513
Kulis M, et al. (2015) Whole-genome fingerprint of the
DNA methylome during human B cell differentiation.
Nature Genetics 47:746–756
Villar D, et al. (2015) Enhancer evolution across 20
mammalian species. Cell 160:554-566
Zepeda-Mendoza CJ, et al. (2015) Quantitative analysis
of chromatin interaction changes upon a 4.3 Mb deletion
at mouse 4E2. BMC Genomics 16:982
2015 EMBL-EBI Annual Scientific Report 84