Annual Scientific Report 2015

The EMBL International
PhD Programme at EMBL-EBI
Students mentored in the EMBL International PhD Programme receive
advanced, interdisciplinary training in molecular biology and bioinformatics.
Theoretical and practical training underpin an independent, focused research
project under the supervision of an EMBL-EBI faculty member and monitored by
a Thesis Advisory Committee comprised of EMBL-EBI faculty, local academics
and, where appropriate, industry partners.
EMBL-EBI is a University Partner Institute of the
University of Cambridge, and in 2015 we benefited
from the presence of 30 PhD students, welcoming five
newcomers. Three students successfully defended their
theses and were awarded PhDs, and one submitted his
thesis. These are showcased below.
Programme events in 2015 at
EMBL-EBI, through the
Training Programme:
• PhD Student Seminar Day at EMBL-EBI;
• Bioinformatics course for second-year EMBL
PhD Programme students, organised and run
by EMBL-EBI students through the Training
Programme;
• EMBL-EBI–Sanger–Cambridge PhD Symposium
(eSCAMPS)
• EMBL PhD Symposium at EMBL Heidelberg;
• Basic Teaching Module at EMBL Heidelberg;
• PhD student-led Lunchtime Seminar series;
• Statistics training course, jointly held with the
Wellcome Trust Sanger Institute at EMBL-EBI.
Selected theses
Ewan Johnstone
An evaluation of cancer subtypes and
glioma stem cell characterisation
Supervisor: Paul Bertone
Ewan applied a novel
co-expression analysis method to
identify independent tumour cell
subtypes within independent co-expression modules.
These modules relate to intuitive biological features,
enabling the user to identify module-specific variation
independently of a transcriptome-wide subtype.
Ewan used this methodology to evaluate established
subtypes in breast ductal carcinoma and glioma. In
breast carcinoma the basal, luminal, Her2-enriched
and claudin-low cancer subtypes were replicated,
revealing functional expression differences that denote
each type. In glioma, dominant expression variation
presented a grade-associated axis of proneural to
mesenchymal expression. This axis was also presented
within individual tumours, suggesting that one should
not assume individual tumours are classified as discrete
subtypes. Ewan’s analysis of glioma-derived stem cell
lines revealed distinct proneural and mesenchymal
clusters in both gene expression and chromatin
accessibility. Proneural signature genes suggested these
lines are similar to normal glial progenitor cells, while
mesenchymal expression largely relates in inflammatory
and immune responses. Ewan was able to analyse
epigenetic control of subtype–signature transcriptional
networks thanks to differential chromatin accessibility
of signatures genes. He also compared glioma-derived
stem cells and neural stem cells to identify gliomaspecific
features. His thsis describes novel methods
for ATAC-seq analysis are also described for the
examination of chromatin accessibility. These findings
will further assist the translation of tumour subtypes
to the clinic alongside deeper characterisation glioma’s
persistent and heterogeneous cancer stem
cell population.
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2015 EMBL-EBI Annual Scientific Report