National Center of Competence in Research - NCCR Molecular Oncology

Dr. Mauro Delorenzi

Dr. Mauro Delorenzi is a specialist in gene expression bioinformatics, Hidden Markov Models and statistical data analysis. He works mostly in biomolecular medicine projects and translational research. Mauro studied molecular biology and statistics in Zürich and received his PhD in 1989 for research on Homeotic Gene Expression in Drosophila. Later, he worked on sequence analysis and genomic data mining in Terry Speed's group at the Walter and Eliza Hall Institute in Melbourne. Since 2002 he is group leader in the NCCR Molecular Oncology program, first at ISREC, and since 2008 at the Swiss Institute of Bioinformatics.

Swiss Institute of Bioinformatics (SIB)

Bioinformatics Core Facility (BCF)

The Bioinformatics Core Facility (BCF) is a research and service group within the Swiss Institute of Bioformatics (SIB). Our core competence and activities reside in the interface between biomedical sciences, statistics and computation, particularly in the application of high-throughput omics tech­nolo­gies, such as gene-expression microarray, to problems of clinical importance, such as development of cancer biomarkers. The BCF offers consulting, teaching and training, data analysis support and research collaborations for both academic and industrial partners.

The BCF was founded in 2002 as a data analysis support group within the NCCR Molecular Oncology, serving mostly biomedical research groups in Lausanne, Switzerland, mainly at the Institute of Experimental Cancer Research (ISREC) and the Centre Hospitalier Universitaire Vaudois (CHUV).

It has since grown to be a full research group within the SIB with widened scope of activities. We are involved in larger projects such as collaborations within European Union projects (TRANSBIG and ACGT), the MAQC2 project coordinated by the FDA, as well as consulting for several industrial partners in the area of statistical aspects of clinical biomarker development

Method Development

The emergence of "omics" science presented challenges in data analysis, both in integrating multiple modes of assays (DNA, RNA, proteins, and everything else) and in integrating heterogeneous, independent datasets (such as multi-center cohorts in clinical studies). We identified the core problems are in the following area:

• Availability of well-curated omics data, along with sample annotations such as clinical outcome
• Adaptation of rigorous statistical methods with good properties to omics data, particularly for dealing with generalizability in discoveries made from omics data, such as in biomarker development, where their performance tend to decrease with expanding test cases
• Implementation of effective and efficient computational methods, for both data management and intensive numerical computation

Biostatistical Support

The BCF provides a consulting service on biostatistics matters, on a mandate from the SIB and the Swiss Confederation. This service is aimed at all people active in life sciences in Switzerland. It includes training and teaching, consulting, data analysis, or research collaboration, with a focus on high-throughput technologies in genomics or proteomics.

The service can be provided on a collaborative basis or for a fee, depending on the circumstances.

For academic groups that require long-term support, we strongly advise to start a discussion at the grant-submission step, and to include a request for a part-time bioinformatician in the grant. By pooling such part-time positions, the BCF is able to offer a longer-term dedicated support.

Expression Data Collection and Curation

Although omics data can viewed as a big matrix of concatenated data with multiple variables (and modes of assays) and samples (from many studies), tremendous effort is required to reformat and standardize mostly unstructured raw data (both private and public) before they can be efficiently used.

Consulting

The BCF provides services, both paid and unpaid, for the planning, experimental design and analysis of projects, and supporting grant proposal writing, resulting in a number of successful grants. We also provide industrial partners with biostatistical and bioinformatics advice, particularly in relation to development and validation of biomarkers.

Data Analysis and Research Collaboration

We can be more involved in solving the client's problem by performing computationally intensive analysis using our tools and computational resources. Here, our members will have prominent role in the project and we supply both data and computational resources.

Personel Embedding

The client may appoint their researchers to work full or part-time, physically within BCF, allowing them to use our resources and be involved in our group activities such as the regular internal meetings, while they are still focusing on the client's project.

List of publications

Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, Andre S, Piccart M, Campone M, Brain E, Macgrogan G, Petit T, Jassem J, Bibeau F, Blot E, Bogaerts J, Aguet M, Bergh J, Iggo R, Delorenzi M. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 15:68-74 (2009)

Meier P, Antonov J, Zbinden R, Kuhn A, Zbinden S, Gloekler S, Delorenzi M, Jaggi R, Seiler C. Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease. Heart 95:900-908 (2009)

Murat A, Migliavacca E, Hussain SF, Heimberger AB, Desbaillets I, Hamou MF, Ruegg C, Stupp R, Delorenzi M, Hegi ME. Modulation of angiogenic and inflammatory response in glioblastoma by hypoxia. PLoS One 4:e5947 (2009)

Norrmen C, Ivanov KI, Cheng J, Zangger N, Delorenzi M, Jaquet M, Miura N, Puolakkainen P, Horsley V, Hu J, Augustin HG, Yla-Herttuala S, Alitalo K, Petrova TV. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol 185:439-457 (2009)

Parisi F, Sonderegger B, Wirapati P, Delorenzi M, Naef F. Relationship between estrogen receptor alpha location and gene induction reveals the importance of downstream sites and cofactors. BMC Genomics 10:381 (2009)

Popovici V, Goldstein DR, Antonov J, Jaggi R, Delorenzi M, Wirapati P. Selecting control genes for RT-QPCR using public microarray data. BMC Bioinformatics 10:42 (2009)

Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, Delorenzi M, Piccart M, Sotiriou C. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 14:5158-5165(2008)

Guipponi M, Toh MY, Tan J, Park D, Hanson K, Ballana E, Kwong D, Cannon PZ, Wu Q, Gout A, Delorenzi M, Speed TP, Smith RJ, Dahl HH, Petersen M, Teasdale RD, Estivill X, Park WJ, Scott HS. An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss. Hum Mutat 29:130-141 (2008)

Kuhn A, Luthi-Carter R, Delorenzi M. Cross-species and cross-platform gene expression studies with the Bioconductor-compliant R package 'annotationTools'. BMC Bioinformatics 9:26 (2008)

Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, Gillet C, Ellis P, Ryder K, Reid JF, Daidone MG, Pierotti MA, Berns EM, Jansen MP, Foekens JA, Delorenzi M, Bontempi G, Piccart MJ, Sotiriou C. Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 9:239 (2008)

Monnier Y, Farmer P, Bieler G, Imaizumi N, Sengstag T, Alghisi GC, Stehle JC, Ciarloni L, Andrejevic-Blant S, Moeckli R, Mirimanoff RO, Goodman SL, Delorenzi M, Ruegg C. CYR61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma. Cancer Res 68:7323-7331 (2008)

Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC, Hainfellner JA, Heppner FL, Dietrich PY, Zimmer Y, Cairncross JG, Janzer RC, Domany E, Delorenzi M, Stupp R, Hegi ME. Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol 26:3015-3024 (2008)

Oberli A, Popovici V, Delorenzi M, Baltzer A, Antonov J, Matthey S, Aebi S, Altermatt HJ, Jaggi R. Expression profiling with RNA from formalin-fixed, paraffin-embedded material. BMC Med Genomics 1:9 (2008)

Schutz F, Delorenzi M. MAMOT: hidden Markov modeling tool. Bioinformatics 24:1399-1400 (2008)

Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J, Bierau K, Hegi ME. Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10:332-337 (2008)

Willi-Monnerat S, Migliavacca E, Surdez D, Delorenzi M, Luthi-Carter R, Terskikh AV. Comprehensive spatiotemporal transcriptomic analyses of the ganglionic eminences demonstrate the uniqueness of its caudal subdivision. Mol Cell Neurosci 37:845-856 (2008)

Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, Haibe-Kains B, Desmedt C, Ignatiadis M, Sengstag T, Schutz F, Goldstein DR, Piccart M, Delorenzi M. Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 10:R65 (2008)

Guipponi, M., Toh, M.Y., Tan, J., Park, D., Hanson, K., Ballana, E., Kwong, D., Cannon, P.Z.F., Wu, Q., Gout, A., Delorenzi, M., Speed, T.P., Smith, R.J.H., Dahl, H.H., Petersen, M., Teasdale, R.D., Estivill, X., Park, W.J., Scott, H.S. An integrated genetic and functional analysis of the role of type II transmembrane serine proteases in hearing loss. Hum Mutat. 29(1):130-4 (2007)

Prandini, P., Deutsch, S., Lyle, R., Gagnebin, M., Delucinge Vivier, C., Delorenzi, M., Gehrig, C., Descombes, P., Sherman, S., Bricarelli, D., Baldo, C., Novelli, A., Dallapiccola, B., Antonarakis, S.E. Natural gene expression variation in Down Syndrome modulates the outcome of gene dosage imbalance. American Journal of Human Genetics, 81:252-63 (2007)

Runne, H., Kuhn, A., Wild, E.J., Wirapati, P., Kristiansen, M., Isaacs, J., Régulier, E., Delorenzi, M., Tabrizi, S.J., Luthi-Carter, R. Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. Proc Natl Acad Sci U S A., 104(36):14424-9 (2007)

Vuaroqueaux, V., Urban, P., Labuhn, M., Delorenzi, M., Wirapati, P., Benz, C.C., Flury, R., Dieterich, H., Spyratos, F., Eppenberger, U., Eppenberger-Castori, S. Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome. Breast Cancer Res. 9(3):R33 (2007) full article [pdf]

Schmid, C.D., Sengstag, T., Bucher, P., Delorenzi, M. MADAP, a flexible clustering tool for the interpretation of one-dimensional genome annotation data. Nucleic Acids Res. 35(Web Server issue):W201-5 (2007)

Kuhn, A., Goldstein, D.R., Hodges, A., Strand, A.D., Sengstag, T., Kooperberg, C., Becanovic, K., Pouladi, M.A., Sathasivam, K., Cha, J.H., Hannan, A.J., Hayden, M.R., Leavitt, B.R., Dunnett, S.B., Ferrante, R.J., Albin, R., Shelbourne, P., Delorenzi, M., Augood, S.J., Faull, R.L., Olson, J.M., Bates, G.P., Jones, L., Luthi-Carter, R. Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet. 16(15):1845-61 (2007)

Loi, S., Haibe-Kains, B., Desmedt, C., Lallemand, F., Tutt, A.M., Gillet, C., Ellis, P., Harris, A., Bergh, J., Foekens, J.A., Klijn, J.G.M., Larsimont, D., Buyse, M., Bontempi, G., Delorenzi, M., Piccart, M.J., and Sotiriou. C. Definition of clinically distinct molecular subtypes in estrogen receptor positive breast carcinomas through use of genomic grade. J. Clin. Oncol. 25(10):1239-46 (2007)

Buyse, M., Loi, S., van't Veer, L., Viale, G., Delorenzi, M., Glas, A. M., d'Assignies, M. S., Bergh, J., Lidereau, R., Ellis, P., Harris, A., Bogaerts, J., Therasse, P., Floore, A., Amakrane, M., Piette, F., Rutgers, E., Sotiriou, C., Cardoso, F., and Piccart, M. J. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98, 1183-1192 (2006)

Gotthardt, D., Blancheteau, V., Bosserhoff, A., Ruppert, T., Delorenzi, M., and Soldati, T. Proteomic fingerprinting of phagosome maturation and evidence for the role of a Galpha during uptake. Mol Cell Proteomics, 5(12):2228-43 (2006)

Hodges, A., Strand, A. D., Aragaki, A. K., Kuhn, A., Sengstag, T., Hughes, G., Elliston, L. A., Hartog, C., Goldstein, D. R., Thu, D., Hollingsworth, Z. R., Collin, F., Synek, B., Holmans, P. A., Young, A. B., Wexler, N. S., Delorenzi, M., Kooperberg, C., Augood, S. J., Faull, R. L., Olson, J. M., Jones, L. , and Luthi-Carter, R. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 15, 965-977 (2006)

Leupin, N., Kuhn, A., Hügli, B., Grob, T.J., Jaggi, R., Tobler, A., Delorenzi, M., and Fey, M.F. Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines. Br. J. Haematol. 135(4), 520-3 (2006)

Menzel, O., Migliaccio, M., Goldstein, D.R., Dahoun, S., Delorenzi, M., and Rufer, N. Mechanisms regulating the proliferative potential of human CD8+ T lymphocytes over-expressing telomerase. J Immunol. 177(6):3657-68 (2006)

Urban, P., Vuaroqueaux, V., Labuhn, M., Delorenzi, M., Wirapati, P., Wight, E., Senn, H. J., Benz, C., Eppenberger, U., and Eppenberger-Castori, S. Increased expression of urokinase-type plasminogen activator mRNA determines adverse prognosis in ErbB2-positive primary breast cancer. J Clin Oncol 24, 4245-4253 (2006)

Sotiriou, C., Wirapati, P., Loi, S., Harris, A., Fox, S., Smeds, J., Nordgren, H., Farmer, P., Praz, V., Haibe-Kains, B., Desmedt, C., Larsimont, D., Cardoso, F., Peterse, H., Nuyten, D., Buyse, M., Van de Vijver, M.J., Bergh, J., Piccart, M., Delorenzi, M. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis, J Natl Cancer Inst. 98(4):262-72 (2006)

Bacac, M., Migliavacca, E., Stehle, J.C., Mckee, T., Delorenzi, M., Coindre, J.M., Guillou, L. and Stamenkovic, I., A gene expression signature that distinguishes desmoid tumors from nodular fasciitis, J Pathol., 208(4):543-53 (2006)

Jagannathan, V., Roulet, E., Delorenzi, M., Bucher, P., HTPSELEX - a database of high-throughput SELEX libraries for transcription factor binding sites. Nucleic Acids Research, 34(Database issue):D90-4 (2006)

Farmer, P., Bonnefoi, H., Becette, V., Tubiana-Hulin, M., Fumoleau, P., Larsimont, D., MacGrogan, G., Bergh, J., Cameron, D., Goldstsein, D., Duss, S., Nicoulaz, A.L., Fiche, M., Brisken, C., Delorenzi, M., Iggo, R., Identification of molecular apocrine breast tumours by microarray analysis. Oncogene, 24:4660-71 (2005)

Jongeneel, C.V., Delorenzi, M., Iseli, C., Zhou, D., Haudenschild, C., Brian, J., Stevenson, B.J., Strausberg, R.L., Simpson, A.J.G., Vasicek, T.J., An atlas of human gene expression from massively parallel signature sequencing (MPSS), Genome Res. 15:1007-14 (2005)

Anderle, P., Sengstag, T., David, M., Mutch, D.M., Rumbo, M., Praz, V., Mansourian, R., Delorenzi, M., Williamson, G., Roberts, M.A.,Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes, BMC Genomics, 6:69 (2005) full article [pdf]

Beckmann, J.S., Maurer, F., Delorenzi, M. and Falquet, L., Ubiquitin ligases as cancer genes, Human Mutation 25: 507-12 (2005)

Anderle P, Sengstag T, Mutch DM, Rumbo M, Praz V, Mansourian R, Delorenzi M, Williamson G, Roberts MA. Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes. BMC Genomics 6, 69 (2005)

de Fourmestraux V., Neubauer H., Poussin C., Farmer P., Falquet L., Burcelin R., Delorenzi M., Thorens B., Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes. Journal of Biological Chemistry, 279, 50743-50753 (2004)

Godard, S., Getz, G., Delorenzi, M., Farmer, P., Kobayashi, H., Desbaillets, I., Nozaki, M., Diserens, A.C., Hamou, M.F., Dietrich, P.Y., Regli, L., Janzer, R.C., Bucher, P., Stupp, R., de Tribolet, N., Domany, E., Hegi, M.E. Classification of human astrocytic gliomas on the basis of gene expression, A correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Research 63, 6613-6625 (2003)

Reviews

Migliavacca, E., Applied Introduction to Multivariate Methods Used in Drug Discovery, Mini Review in Medicinal Chemistry 3, 831-843 (2003)

Scientifics articles in anthologies

Goldstein, D.R., Delorenzi, M. Statistical Design and Data Analysis for Microarray Experiments. A. Berger and M.A. Roberts (eds)., Unraveling Lipid Metabolism with Microarrays. Dekker, New York, USA (2003)

Anderle, P., Berger, A., Farmer, P.J., Roberts, M.A. Dietary long chain fatty acid induction of gene signals involved in carcinogenesis. A. Berger and M.A. Roberts (eds)., Unraveling Lipid Metabolism with Microarrays. Dekker, New York, USA (2003)

Anderle, P., Farmer, P.J., Berger, A., Roberts, M.A. A Nutrigenomic Approach to Understanding the Mechanisms by which Dietary Long Chain Fatty Acids Induce Gene Signals and Control Mechanisms involved in Carcinogenesis. A. Berger and M.A. Roberts (eds)., Unraveling Lipid Metabolism with Microarrays. Dekker, New York, (2003)

Book Chapters

Goldstein, D.R., Delorenzi, M., Luthy-Carter, R. and Sengstag, T. book chapter: Meta-Analysis of Microarray Studies. In in Rudy Guerra and David Allison (eds) Meta-Analysis and Combining Information in Genetics, Chapmann-Hall (2006)