Sep 29, 2013 (4 years and 8 months ago)


This year, we continued our work of focusing on gene
expression and Next Generation Sequencing (NGS)
analyses. We improved our existing cancer genomics
pipeline and associated visualisation tools, upgrading its
performance and functionality, and including many of the
methods used for QC, variant calling – including indels
– and somatic mutation consequence in international
cancer genome projects. Our pipeline also provides basic
input data to the Personalised Medicine Tool developed
in Alfonso Valencia's laboratory. We have also improved
the methodologies for the analysis of RNA-seq, ChIP-
seq, MethylC-seq and PCR-seq experiments.
Our efforts in the development of custom methods for
miRNA target determination and its statistical evalua-
tion led to several exciting collaborations, including the
study of the combinatorial effects of miRNAs on the Myc
pathway in lymphomas (Figure), and their role in Diffuse
Large B-cell Lymphoma (DLBCL). We implemented an
approach that combines gene expression and miRNA
expression results in a web-based tool (miRGate) which
relies on an extensive database of common 3'-UTR
sequences to compute the predictions of several well-
known miRNA target determination methods.
Finally, in 2011, the Unit organised courses on the statis-
tical computer language R, sequence analysis, genomic
browsing and gene expression analysis, which gathered
more than 150 in-house and external attendees.
W e d e fi n e G e n e t i c
I n t e r a c t i o n s ( G I ) a s t h e
n u m b e r o f d o w n r e g u l a t e d
m i R N A g e n e s t h a t c a n
p o t e n t i a l l y t a r g e t s p e c i fi c
s e q u e n c e s i n a l l p o s s i b l e
3'- U T R s o f t h e i n d i c a t e d
o v e r e x p r e s s e d g e n e. T h e
a s s o c i a t e d m e t h o d a l l o w s
s t a t i s t i c a l e v a l u a t i o n o f t h e
m o s t e n r i c h e d m i R N A -
g e n e r e l a t i o n s h i p s. M y c
i s t h e o v e r e x p r e s s e d g e n e
w i t h t h e h i g h e s t n u m b e r
o f s t a t i s t i c a l l y s i g n i fi c a n t
G I i n T - c e l l l y m p h o m a s
( B u e n o M.J. e t a l., Blood
Quesada V, et al. (2011). Exome sequencing
identifies recurrent mutations of the splicing
factor SF3B1 gene in chronic lymphocytic
leukemia. Nat Genet 44, 47-52.
Puente XS, et al. (2011). Whole-genome
sequencing identifies recurrent mutations in
chronic lymphocytic leukaemia. Nature 475,
Bueno MJ, et al. (2011). Combinatorial effects
of microRNAs to suppress the Myc oncogenic
pathway. Blood 117, 6255-6266.
Montes-Moreno S, et al. (2011). miRNA expres-
sion in diffuse large B-cell lymphoma treated with
chemoimmunotherapy. Blood 118, 1034-1040.
López-Fernández H, Glez-Peña D, Reboiro-
Jato M, Gómez-López G, Pisano DG, Fdez-
Riverola F (2011). PileLineGUI: a desktop
environment for handling genome position
files in next-generation sequencing studies.
Nucleic Acids Res 39, W562 -W566.
Marenne G, et al. (2011). Assessment of copy
number variation using the Illumina Infinium
1M SNP-array: A comparison of methodologi-
cal approaches in the Spanish Bladder Cancer/
EPICURO Study. Hum Mutat 32, 240-248.
Rodriguez-Nieto S, Cañada A, Pros E, Pinto AI,
Torres-Lanzas J, Lopez-Rios F, Sanchez-Verde L,
Pisano DG, Sanchez-Cespedes M (2011). Mas-
sive parallel DNA pyrosequencing analysis of
the tumor suppressor BRG1/SMARCA4 in lung
primary tumors. Hum Mutat 32, E1999-E2017.
Swat A, Dolado I, Igea A, Gomez-Lopez G,
Pisano DG, Cuadrado A, Nebreda AR (2011).
Expression and functional validation of new
p38a transcriptional targets in tumorigenesis.
Biochem J 434, 549-558.
Villasante A, Piazzolla D, Li H, Gomez-Lopez
G, Djabali M, Serrano M (2011). Epigenetic
regulation of Nanog expression by Ezh2 in
pluripotent stem cells. Cell Cycle 10, 1488-1498.
Fernández-Ramires R, et al. (2011).
Transcriptional characteristics of familial non-
BRCA1/BRCA2 breast tumors. Int J Cancer 128,
Javierre BM, et al. (2011). Long-range
epigenetic silencing associates with
deregulation of ikaros targets in colorectal
cancer cells. Mol Cancer Res 9, 1139-1151.
Glez-Peña D, Gómez-López G, Reboiro-
Jato M, Fdez-Riverola F, Pisano DG (2011).
PileLine: a toolbox to handle genome position
information in next-generation sequencing
studies. BMC Bioinformatics 12, 31-31.
Guillamot, M, Manchado E, Chiesa M, Gómez-
López G, Pisano DG, Sacristán M, Malumbres
M (2011). Cdc14b regulates mammalian
RNA polymerase II and represses cell cycle
transcription. Sci Reports 1, 189.
daVid g. pisano UNIT hEAD
Core Unit Head
David G. Pisano
Eduardo Andrés, Ángel
Carro, Gonzalo Gómez,
Osvaldo Graña
The Bioinformatics Core Unit supports CNIO research-
ers with management, integration and quantitative
computational analysis of high-throughput data. This
includes the assessment of computational and numeri-
cal methods, the development of custom software tools,
the implementation of automatised analysis pipelines,
bioinformatics training and the maintenance of a high-
performance computing infrastructure.
This year the Unit participated in a wide range of col-
laborative projects in the areas of cancer genomics
and transcriptomics, focusing especially on the roles
of resequencing and microRNAs in cancer.
Our Unit's main objectives are to:
Deliver bioinformatics analysis services and scientific
computing technologies to CNIO scientists.
Implement state-of-the-art computational solutions
(both hardware and software-based) associated to
the analysis of massively-generated experimental
Provide custom assessment and training in
bioinformatics methods.
Help CNIO researchers to integrate and understand
quantitative biological information.