1. Bioinformatics for genomics Kickoff Bioinformatics Expertise Center 10 November 2009 Judith Boer Dept. of Human Genetics

2. Omics views of genomes RNA expression Gene structure Genetic variationExpression variation DNA methylation Chromatin Epigenetic variation SNPs, loss-of-heterozygosity Copy number variants

3. Who are we? Johan den Dunnen  always new machines Peter-Bram ‘t Hoen  always new applications Barend Mons  biosemantics Peter Taschner  databases and annotation Matt Hestand  next generation sequencing analysis Judith Boer  microarray and integrated analysis

4. Bioinformatics at Human Genetics Personal view: "Life science researchers should be able to analyze and interpret their own genomics data" Tools Courses Research - example Expertise

5. Bioinformatics Tools – Commercial Rosetta Resolver database, analysis, visualization Spotfire analysis and visualization Ingenuity Pathway Analysis literature and high-throughput database mining Dedicated platform tools Agilent, Illumina, Affymetrix: image analysis, per array www.lgtc.nl

6. Bioinformatics Tools – Open source Programming languages R, Perl, Bash scripting (Linux), MySQL, Apache, PHP, Python, Java, … Software, e.g. Bioconductor, BioPerl, Ensembl Perl API, Bowtie, BWA, Velvet, Varscan, Rmap, … Alignment, analysis of next-generation sequencing and microarray data Web browsers, e.g. UCSC, Ensembl visualize data in relation to genome features Gene Ontology, e.g. DAVID functional annotation and enrichment

7. Bioinformatics Research & Tools BioSemantics Databases and annotation Next generation sequencing analysis Microarray and integrated analysis www.humgen.nl/bioinformatics.html www.lgtc.nl

8. Bioinformatics Tools – BioSemantics Anni 2.1 (Jelier / Mons / 't Hoen) associations between gene list and other genes, diseases, processes based on literature mining Nermal (van Haagen / Mons / 't Hoen) which proteins associate with / bind to my protein?

9. Bioinformatics Tools – NGS analysis GAPSS (Hestand / van Galen / 't Hoen) modular pipeline for next-generation sequencing data analysis CORE_TF (Hestand / 't Hoen) Conserved and Over-REpresented Transcription Factor binding sites

10. Bioinformatics Tools – Databases LOVD (Fokkema / Taschner) www.lovd.nl locus-specific DNA variation database Mutalyzer (Fokkema / Taschner) sequence variant nomenclature check

11. Bioinformatics Tools – Microarray analysis Microarray Retriever (Brandt / 't Hoen) search and retrieve data from public array repositories R packages (Menezes / van Iterson / Boer) SIM: Statistical Integration of Microarrays SSPA: Sample Size and Power Analysis for microarray data

12. Bioinformatics Courses Analysis of microarray gene expression data (MGC) Judith Boer, Peter van der Spek (ErasmusMC) 10th edition June 2010 (yearly, 30-40 participants PhD/PD) Next-generation sequencing data analysis (MGC) Johan den Dunnen, Judith Boer, Matt Hestand 3rd edition planned February 2010 www.medgencentre.nl others: MolMed Research School ErasmusMC, NBIC

13. Bioinformatics Research – Example Next generation sequencing data analysis ChIP-seq gene structure (DeepCAGE) expression analysis (DeepSAGE) miRNA expression and identification (targeted) re-sequencing mutation (SNP) detection copy number variation detection de novo assembly

14. Bioinformatics Expertise Experimental design of microarray and NGS studies Choice of analysis software Use of analysis software Setting up a locus-specific database Some cases: help with data analysis

15. Acknowledgements BioSemantics: Herman van Haagen, Bharat Singh, Peter-Bram ‘t Hoen, Marco Roos, Barend Mons Databases and annotation: Ivo Fokkema, Jacopo Celli, Gerard Schaafsma, Jeroen Laros, Peter Taschner NGS analysis: Michiel van Galen, Jaap van der Heijden, Yuching Lai, Henk Buermans, Matthew Hestand Microarray analysis: Maarten van Iterson, Judith Boer Michel Villerius, Johan den Dunnen, Gertjan van Ommen