Norsk Regnesentral

Statistical Methods in Bioinformatics at NR

The genome is the genetic material in a cell; the blueprint of life. The functional units of the genome are called genes. Sequencing the genome consists in identifying the position and DNA-sequence of each gene. The genome of many organisms is now fully sequenced, and important milestones in sequencing the human genome have been reached. We have thus moved from the pre-genome era to the post-genome era. The most important challenge in the post-genome era is to understand the role of each gene. This is called functional genomics. Functional genomic research can e.g. provide a better understanding of how an individual's genetic inheritance affects the body's response to drugs, thus providing better diagnosis and treatment of different diseases.

New techniques, for example DNA microarrays, make it possible to study the role of thousands of genes simultaneously. Such techniques produce enormous amounts of data. Bioinformatics merges these new techniques with advanced statistical methods and computer science technology to organize, analyze and interpret data. NR has identified problems where our statistical competence is vital in transforming huge amounts of functional genomics data into important pieces of knowledge.

We currently participate in the Norwegian Bioinformatics Platform (a FUGE platform). In addition, NR is a partner in a project on statistical genomics, aimed at educating and supervising UiO students and staff in experimental design and statistical analysis of microarray experiments. Several of the projects in the innovation area health of the SFI Statistics for Innovation are within the area of bioinformatics.

Research in Statistical Methods in Bioinformatics is organized under the research and market area of Statistics for the Environment, Marine Resources and Health at the SAMBA department of the Norwegian Computing Center.

Courses
Publications
Handouts from talks
More information

Courses

  • Course in finding differentially expressed genes from microarray data, Oslo, May 31, 2006. This is part of the course Microarray data analysis held from May 30 to June 2, 2006.
    Lecturers May 31, 2006: Marit Holden, Ola Haug and Arnoldo Frigessi, Norwegian Computing Center.
  • Course in Statistics and Bioinformatics held at Norwegian Computing Center, Oslo, March 9-10, 2005.
    Lecturers: Marit Holden, Anders Løland, Linda Reiersølmoen Neef, Ola Haug and Arnoldo Frigessi, Norwegian Computing Center.
  • Course in statistics for molecular biologists held at the Computational Biology Unit, HiB, Bergen, December 7-8, 2004.
    Lecturer: Marit Holden, Norwegian Computing Center.

Publications

Marit Holden, Ingrid Glad, Håvard Hauge, Evind Hovig, Knut Liestøl. Image restoration and analysis of biomolecular radioactivity images II NR Note SAMBA/11/2012. March 2012.

Reikvam, Håkon; Mosevoll, Knut Anders; Melve, Guro Kristin; Günther, Clara-Cecilie; Sjo, Malvin; Bentsen, Pål-Tore; Bruserud, Øystein The Pretransplantation Serum Cytokine Profile in Allogeneic Stem Cell Recipients Differs from Healthy Individuals, and Various Profiles are Associated with Different Risks of Posttransplantation Complications Biology of Blood and Marrow Transplantation 2012 18(2):190-199.

Sandve, Geir K.; Gundersen, Sveinung; Rydbeck, Halfdan; Glad, Ingrid; Holden, Lars; Holden, Marit; Liestøl, Knut; Clancy, Trevor; Drabløs, Finn;Ferkingstad, Egil; Johansen, Morten; Nygaard, Vegard; Tøstesen, Eivind; Frigessi, Arnoldo; Hovig, Eivind The differential disease regulome BMC Genomics 2011 12(1):353.

Halle, Cathinka; Lando, Malin; Svendsrud, Debbie H.; Clancy, Trevor; Holden, Marit; Sundfør, Kolbein; Kristensen, Gunnar B.; Holm, Ruth; Lyng, Heidi Membranous Expression of Ectodomain Isoforms of the Epidermal Growth Factor Receptor (EGFR) Predicts Outcome after Chemoradiotherapy of Lymph Node Negative Cervical Cancer Clinical Cancer Research 2011 17(16):5501-5512.

Jemtland, Rune; Holden, Marit; Reppe, Sjur; Olstad, Ole K,; Reinholt Finn P,; Gautvik, Vigdis T,; Refvem, Hilde; Frigessi, Arnoldo; Houston Brian; Gautvik, Kaare M Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype Journal of Bone and Mineral Research 2011 26(8):1793-801

Sandve, Geir K.; Gundersen, Sveinung; Rydbeck, Halfdan; Glad, Ingrid; Holden, Lars; Holden, Marit; Liestøl, Knut; Clancy, Trevor; Ferkingstad, Egil; Johansen, Morten; Nygaard, Vegard; Tøstesen, Eivind; Frigessi, Arnoldo; Hovig, Eivind The Genomic HyperBrowser: inferential genomics at the sequence level Genome biology 2010 11:R121, Issue 12.

Bøhn Siv K.; Myhrstad, Mari C.; Thoresen, Magne; Holden, Marit; Karlsen, Anette; Tunheim, Siv H.; Erlund, Iris; Svendsen, Mette; Seljeflot, Ingebjørg; Moskaug, Jan Ø.; Duttaroy, Asim K.; Laake, Petter; Arnesen, Harald; Tonstad, Serena; Collins, Andrew; Drevon, Christian A.; Blomhoff, Rune Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers BMC Medicine 2010 8:54.

Sjur Reppe, Hilde Refvem; Vigdis T. Gautvik, Ole K. Olstad, Per I. Høvring, Finn P. Reinholt, Marit Holden, Arnoldo Frigessi, Rune Jemtland, Kaare M. Gautvik. Eight genes are highly associated with BMD variation in postmenopausal Caucasian women. Bone March 2010 46(3):604-612, Epub 2009 Nov 14.

Malin Lando, Marit Holden, Linn C. Bergersen, Debbie H. Svendsrud, Trond Stokke, Kolbein Sundfør, Ingrid K. Glad, Gunnar B. Kristensen, Heidi Lyng Gene Dosage, Expression, and Ontology Analysis Identifies Driver Genes in the Carcinogenesis and Chemoradioresistance of Cervical Cancer. PLoS Genetics Nov 2009 5(11): e1000719.

Marit Holden, Shiwei Deng, Leszek Wojnowski, Bettina Kulle GSEA-SNP: applying gene set enrichment analysis to SNP data from genome-wide association studies Bioinformatics 2008 24(23):2784-2785.

Marit Holden, Ingrid Glad, Håvard Hauge, Knut Liestøl. Image restoration and analysis of biomolecular radioactivity images NR Note SAMBA/27/08. June 2008.

Vigdis Nygaard, Fang Liu, Marit Holden, Winston P Kuo, Jeff Trimarchi, Lucila Ohno-Machado, Connie L Cepko, Arnoldo Frigessi, Ingrid K Glad, Mark A van de Wiel, Eivind Hovig, Heidi Lyng. Validation of oligoarrays for quantitative exploration of the transcriptome BMC Genomics 2008 9:258.

Hege Bøvelstad, Ståle Nygård, Hege Størvold, Magne Aldrin, Ørnulf Borgan, Arnoldo Frigessi, Ole Christian Lingjærde. Predicting survival from microarray data - a comparative study Bioinformatics 2007 23(16):2080-2087.

Hans-Olav Fjærli, Geir Bukholm, Camilla Skjæret, Marit Holden, Britt Nakstad. Cord blood gene expression in infants hospitalized with respiratory syncytial virus bronchiolitis Journal of Infectious Diseases 2007 196:394-404.

Hans-Olav Fjærli, Geir Bukholm, Anne Krog, Camilla Skjæret, Marit Holden, Britt Nakstad. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis BMC Infectious Diseases 2006 6:175.

Mark A. van de Wiel, Marit Holden, Ingrid K. Glad, Heidi Lyng, Arnoldo Frigessi. Bayesian Process-Based Modeling of Two-Channel Microarray Experiments: Estimating Absolute mRNA Concentrations, in Bayesian Inference for Gene Expression and Proteomics, edited by Kim-Anh Do, Peter Müller and Marina Vannucci, 2006, pages: 75-96.

Jeanne-Marie Berner, Christophe Müller, Marit Holden; Junbai Wang, Eivind Hovig, Ola Myklebost. Sampling Effects on Gene Expression Data from a Human Tumour Xenograft Scandinavian Journal of Laboratory Animal Science 2006 33(1):17-30.

Vigdis Nygaard, Marit Holden, Anders Løland, Mette Langaas, Ola Myklebost, Eivind Hovig. Limitations of mRNA amplification from small-size cell samples BMC Genomics 2005 6:147.

Arnoldo Frigessi, Mark A. van de Wiel, Marit Holden, Debbie H. Svendsrud, Ingrid K. Glad and Heidi Lyng. Genome-wide estimation of transcript concentrations from spotted cDNA microarray data Nucleic Acids Research - Methods Online 2005;33(17):e143.

Lina Cekaite, Ola Haug, Ola Myklebost, Magne Aldrin, Bjørn Østenstad, Marit Holden, Arnoldo Frigessi, Eivind Hovig and Mouldy Sioud. Analysis of the humoral immune response to immunoselected phage-displayed peptides by a microarray-based method. Proteomics 2004 Sep;4(9):2572-2582.

Arnoldo Frigessi, Mark A. van de Wiel, Marit Holden, Ingrid K. Glad and Heidi Lyng. Model-based estimation of transcript concentrations from spotted microarray data. NR Report 999, ISBN 82-539-0507-6. May 2004. A web page with a program for estimating the model parameters is found here.

Turid Follestad, Mette Langaas, Håvard Rue, Marit Holden and Anders Løland. glme: a C-program for parameter estimation using Gibbs-sampling in large linear mixed-effects models, with applications to DNA microarray data NR Note SAMBA/10/04. March 2004.

Marit Holden and Ola Haug. Experimental design and statistical analysis of SNP data obtained in genetic association studies NR Note SAMBA/28/03. December 2003. The corresponding web pages are found here.

Marit Holden og Anders Løland. Introduksjon til analyse av cDNA mikromatrisedata. Norsk Epidemiologi 2003 13 (2):291-296.

Vigdis Nygaard, Anders Løland , Marit Holden, Mette Langaas, Håvard Rue, Fang Liu, Ola Myklebost, Øystein Fodstad, Eivind Hovig and Birgitte Smith-Sørensen. Effects of mRNA amplification on gene expression ratios in cDNA experiments estimated by analysis of variance. BMC Genomics 2003 4:11.

Tor-Kristian Jenssen, Mette Langaas, Winston P. Kuo, Birgitte Smith-Sørensen, Ola Myklebost, Eivind Hovig. Analysis of repeatability in spotted cDNA microarrays Nucleic Acids Res. 2002 30:3235-3244. See Remarks to paper.

M. Langaas. Bioinformatikk - et interessant forskningsfelt for statistikere? Artikkel skrevet til Norsk Statistisk Forenings tidsskrift Tilfeldig Gang [pdf]

K. Aas. Microarray Data Mining: A Survey NR Note SAMBA/02/01. February 2001.

Statistical Methods in Bioinformatics. NR Information sheet.

Handouts from talks

  • Introductory microarray course; statistics [pdf]. Talk at the introductory microarray course given by The Norwegian Microarray Consortium, Oslo (May 18 and 19, 2009).
  • Introductory microarray course; statistics [pdf]. Talk at the introductory microarray course given by The Norwegian Microarray Consortium, Oslo (May 26, 2008).
  • Steps in a microarray study [pdf]. Talk at the seminar on microarray technologies arranged by the Rikshospitalet-Radiumhospitalet Medical Center, Oslo (November 24, 2006).
  • Parallelization of TransCount - making MCMC parallel for huge datasets [Slides]. Talk at the conference High Performance Computing for Statistical Inference, Dublin (August 23-25, 2006).
  • Model-based estimation of transcript concentrations from spotted microarray data [pdf]. Talk at the 25th European Meeting of Statisticians, Oslo (July 24-28, 2005).
  • Limitations of mRNA amplification from small-size cell samples . Talk at the IBS Nordic Conference, Oslo, (June 2 to June 4, 2005) [pdf] and at the 25th European Meeting of Statisticians, Oslo (July 24-28, 2005) [pdf].
  • Logic regression used for statistical analysis of SNP data obtained in genetic association studies [pdf]. Talk at UMB, Ås, June 14, 2005.
  • Experimental design and non-random variation [pdf] and Identifying expression differences in cDNA microarray experiments [pdf] Talks at the courses "Introduction to Microarray Technology" and "Microarray Data Analysis" at the Norwegian Radium Hospital, Oslo, in November 2004, May 2005, and December 2005.
  • Model-based estimation of transcript concentrations from spotted microarray data [pdf]. Talk at the workshop Statistics in Functional Genomics, Ascona, Switzerland (June 27 to July 2, 2004).
  • Introduction to experimental design and statistical analysis in genetic association studies [pdf] and Combining SNP and microarray data: a discussion of one example from the literature, and some further ideas more in general on clinical data and SNPs [pdf]. Talks at the reach-out day with theme Statistical service on experimental design and analysis of SNP experiments, Oslo (May 7, 2004).
  • Experimental design, repeated measurements and control spots [pdf]. Talk at the user course in microarray technology at the Norwegian Radium Hospital, Oslo (November 27, 2003), at Ahus (December 1, 2003) and at the course in microarray data analysis at Bergen Centre for computational sciences (February 3, 2004).
  • Estimation of absolute mRNA concentrations from cDNA microarrays [pdf]. Talk at Norevent's 3rd Lysebu meeting Oslo (September 8, 2003).
  • Experimental design, repeated measurements and controls [pdf]. Talk at the user course in microarray technology at the Norwegian Radium Hospital, Oslo (May 14 and 21, 2003).
  • Investigating the linearity of an RNA-amplification protocol using analysis of variance on data from cDNA microarray experiments [pdf]. Talk at the 19th Nordic Conference on Mathematical Statistics, Stockholm, Sweden (June 9-13, 2002).
  • Handouts from talks from seminar activities at NR in 2002, presenting new and interesting statistical articles on analysis of gene expression data, are found here.
  • Image analysis of cDNA microarray data [pdf]. Talk at the seminar series on statistical methods in bioinformatics at Norwegian Computing Center (November 1, 2001).
  • Bioinformatikk - et interessant forskningsfelt for statistikere [pdf]. Foredrag på det 11. møte til Norsk Statistisk Forening, Ulvik (June 20, 2001).
  • Statistical Methods in Bioinformatics at NR [pdf]. Informal presentation at seminar series on Computational Biology / Bioinformatics at Department of Computer and Information Science, NTNU (May 9, 2001).
  • Bioinformatikk - en innføring fra en statistikers ståsted [pdf]. Foredrag på seminar i Norsk Statistisk Forening - Avd. Oslo (May 8, 2001).
  • Bioinformatics -- an interesting area of research for statisticians (in Norway)?[pdf]. Talk at seminar series in medical statistics at the University of Oslo (February 15, 2001).

More information

For more information about statistical methods in bioinformatics at the Norwegian Computing Center please contact Chief Research Scientist Marit Holden.