Biomedicine The background. The main interest. The tools

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2 Biomedicine The background The main interest? Bioinformatics Clinical informatics The tools 2

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5 Working on Network Data Analysis HH RR Infrastructure Training BIOCOMPUTATION & STRUCTURAL BIOLOGY PROGRAM BIOINFORMATICS UNIT Biological data Molecular Biology of Childhood Tumors FB CHUVI 5

6 CNIO Molecular Oncology (Dr. Maria Blasco) Structural Biology & Biocomputation (Dr. Alfonso Valencia) Molecular Pathology (Dr. M. A. Piris) Human Cancer Genetics (Dr. Javier Benítez) Experimental Therapies (Dr. James R. Bischoff) Biotechnology (Dr. Ignacio Casal) 6

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8 CNIO Bioinformatics Unit & PDG Group. David Gonzalez. Pisano (Head) Eduardo Andrés (CNIO) Angel Carro (CNIO) Andrés Cañada (INB) Jose Maria Fdez.(UBio) Jaime Fdez. Vera (PDG) Gonzalo Gómez (CHUVI-INB) Osvaldo Graña (UBio) Jose Manuel Rodríguez. (INB) PDG Group 8

9 Bioinformatics Group. (FICHUVI - Universidade de Vigo) Enrique Caso (Head) Florentino Fdez. Riverola (Head) Gonzalo Gómez (Postdoc) Daniel Gonzalez (PhD Student) Pablo Vicente Carrera (Student) Alberto Molares (PhD Student) Carmen M. Redondo (Postdoc) 9

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11 Research lines 11

12 Research lines. B-cell lymphomas functional analysis. Almost 200 B-cell lymphomas 8 clinical subtypes Clustering analysis 12

13 Research lines. B-cell lymphomas functional analysis. Gene Set Enrichment Analysis of NFKB pathway genes in Follicular and Burkitt Lymphomas using Biocarta annotations. Figure 1. Applying Kolmogorov-Smirnof test to find assymmetries in expression levels of functional related blocks of genes, NFKB pathway genes was found enriched in Follicular lymphomas in comparison to Burkitt lymphomas. Figure 2. Heatmap for expression values of those genes involved in NFKB pathway. Figure 3. Map of interactions for NFKB pathway related genes. Figure 3 Figure 1 Figure 2 13

14 Research lines. B-cell lymphomas transcriptome. Clustering the behaviour of whole pathways in B-cell lymphomas. 14

15 Research lines. Genetic Instability in Ewing Sarcomas. -Gene Set Enrichment Analysis of Cytobands and Pathways in Ewing Sarcomas.. Confirmed gains in chromosomes 5, 8,13,14,18 by enrichment analysis. Based on CNA and expression profiling we found G2 pathway, TNFR2, ATBRCA and other pathways enriched in stable vs unstable (3 or more aberrations) phenotypes. - Statistical multivariate analysis support the statistically significant relationship between genetic stability and survival of patients. SUBMITTED TO ONCOGENE. 15

16 Research lines. Role of DAX1 in Ewing s sarcoma. GE Whole genome arrays: GFP shrna EWS/FL1 shrna DAX shrna 16

17 Research Lines. Lung Adeocarcinoma Healthy/Tumoral/Peritumoral markers. Healthy distant tissue (H) 2 cm Healthy periphery tumour tissue (P) Tumour tissue (T) RNA isolation Analyzed tissues sscdna dscdna crna Bioinformatics analysis Affymetrix HG FocusArray crna fragments quality control 17

18 Research Lines. Lung Adeocarcinoma Healthy/Tumoral/Peritumoral markers. Functional analysis for differentially expressed genes in lung adenocarcinoma. 24 genes were found capable to discriminate among surgical classes (healthy, peritumoral and tumoral). 18

19 Research Lines. CpGs in EBV. 19

20 Research lines CARGO: Cancer And Related Genes On Line CARGO: a web portal to integrate customized biological information. Cases I, Pisano DG, Andres E, Carro A, Fernandez JM, Gomez-Lopez G, Rodriguez JM, Vera JF, Valencia A, Rojas AM. Nucleic Acids Res May

21 Research Lines CARGO: Cancer And Related Genes On Line 21

22 Industry Collaborations. Pharmamar. Effects of Yondelis treatment on sensitive and resistant cell lines. Functional analysis of microarrays points to effects on G2 pathway.. Experimental data support this analysis. 22

23 Academic Activities. -1 st Course on Functional Analysis (CNIO). -Summer School in Bioinformatics (UCM). -PhD Course in Bioinformatics (UAM). 23

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25 Software tools 25

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27 Target journals & conferences B-Cell Lymphomas transcriptome: Transcriptome classification of B-cell non-hodgkins lymphoma Mohit Aggarwal, Miguel A. Piris, Raquel Villuendas, Abel Sánchez-Aguilera, Nerea Martínez, Alberto Pérez, Paloma de la Cueva, María Jesús Artiga, Fatima Al-Sharour, Joaquín Dopazo, Gonzalo Gomez, Elena Ruiz-Ballesteros, Francisca I.Camacho, José A.García-Marco CNIO Cancer Conferences Molecular Mechanisms in Lymphoid Neoplasm Madrid, February Poster. Pending to be submitted to Nature Genetics. Genetic Instability in Ewing Sarcomas: Ewing s sarcomas integrated expression and arraycgh profiling reveals distinct genomic instability patterns associated with DNA repair and cell cycle checkpoint pathways Bibiana I. Ferreira (1), Javier Alonso (2) (*), Jaime Carrillo (2), Francesco Acquadro (1), Cristina Largo (1), Javier Suela (1), Manuel R. Teixeira (3); Nuno Ceveira (3), Alberto Molares (4), Gonzalo Goméz-López (4) (5), Ángel Pestaña (2), Ana Sastre (6), Purificacion Garcia-Miguel (6), and Juan C. Cigudosa (1) (*). Oncogene. On revision. Lung Adenocarcinomas Healthy/Tumoral/Peritumoral markers: crna Microarrays and Bioinformatics application in lung carcinoma samples. A.Molares, E.Carrillo, G.Gómez, G. Muñoz Molina, I. Muguruza, I.Sanchez, R.Moreno, V.Leiro, F.Carrillo, E.Caso. 5 th European Conference on Computational Biology, Eliat, Israel , Enero Poster. 27

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29 Main Interests 29

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31 Collaboration offered 31

32 Acknowledgements. UBio staff & PDG group Lymphoma s group Miguel Angel Piris Raquel Villuendas Mohit Aggarwal Cytogenetics group Juan C. Cigudosa Bibiana Ferreira. Childhood tumors group Javier Alonso CHUVI Bioinformatics group Enrique Caso Carmen M. Redondo Alberto Molares F. Fdez-Riverola Epigenetics group. Agustín Fernández. 32