1. ICMB @ Geuvadis achievements and contributions Robert Häsler, functional genomics

2. 2 ICMB achievements mRNA & miRNA sequencing mRNA 72 samples sequenced miRNA 24/72 samples already sequenced high (rank) similarities of results between sites

3. 3 ICMB potential contributions (I) nTARs workflow (novel transcriptional active region) covered regions known? mapping no nTar yes sequence QC no discard hit bad linked to known exon/other nTar? OK BLAT of high quality unmapped reads no discard hit no RF + start codon yes RF no UTR, intron isoform part yes nTar / isoform yes duplication? BLAT + unique flag known elongation? BLATblast like alignment tool RFreading frame ICMB references: Philip et al 2012 Bioinformatics, Klostermeier et al 2011 BMC Genomics

4. 4 ICMB potential contributions (II) detection of splice variation patterns isoform 1 isoform 2 isoform 3 isoform 4 GYN NAG GYN NAG GYN NAG GYN NAG expression values by cufflinks mid high low very low example scenario

5. 5 ICMB potential contributions (II) detection of splice variation patterns isoform 1 isoform 2 isoform 3 isoform 4 GYN XYN NAG GYN XYN NAG GYN XYN NAG GYN XYN NAG expression values by cufflinks example scenario none low very low variant introduced ICMB references: Brosch et al 2012 Cell Metab, Häsler et al 2011 Eur J Cell Biol, Kramer et al 2011 Genetics, ElSharawy et al 2009 Human Mutat, Hiller et al 2008 RNA; Szafranski et al 2007 Genome Biol, Hiller et al 2006 Am J Hum Genet, Hiller et al 2004 Nat Genet

6. 6 ICMB potential contributions (III) linking miRNA & miRNA-targets 2% encoding vs. 60-70% non-coding RNA 10-30% of all genes regulated by miRNAs experimental miR target prediction expensive, slow in silico miR target prediction ~3000 targets/miRNA low/no overlap between different prediction tools

7. 7 ICMB potential contributions (III) linking miRNA & miRNA-targets TASSDB (Sinah et al, 2012) tandem splice site data base how to? sequence pattern donor/acceptor position conservation nonsense mediated decay extract available information: is there a splice-relevant variant? is the variant associated to modified mRNA expression? expected outcome: candidates of variants from the 1000 Genomes project with potential functional impact ICMB references: Häsler et al 2012 PLoS One, Keller et al 2011 Nat Methods, Schulte et al 2010 NAR, Sinha et al, 2010 BMC Bioinformatics, Hiller et al 2007 NAR

8. 8 ICMB potential contributions summary nTARs splice variation patterns linking miRNA to miRNA targets our position in the analysis pipeline? team Philip Rosenstiel Stefan Schreiber Robert Häsler Matthias Barann Daniela Esser Markus Schilhabel