Research Report 2010 - MDC

Structure of the GroupChristoph DieterichGroup LeaderDr. Christoph DieterichProgrammersMatthias DodtDominic TölleGraduate StudentsSebastian FröhlerZisong ChangSystem administratorAndreas KuntzagkSecretariatSabrina DeterStart of group:April 2009Bioinformatics inOuantitative BiologyBioinformatics is a highly dynamic discipline, which operates at the interface of life sciences,computer science and formal sciences. Currently, emerging technologies in nucleic acidssequencing, mass spectrometry and imaging revolutionize biology. For the first time, a holisticquantification of biological systems at the level of genomes, transcripts, proteins andmetabolites is in reach. Bioinformatics supports this technology-driven transition of biologyinto a truly quantitative science.We use existing and develop novel methods for high-throughput data acquisition, processing,model building and inference. Computational studies are backed up by experimental workwithin our group and within active collaborations.Computational approaches to study eukaryoticgene regulationThe expression of a gene is directly regulated by interactionsof proteins and nucleic acids or by RNA-RNAinteractions. We work on statistical methods for regulatorymotif (e.g. binding site) and module (e.g. promoterelements) prediction. Lately, we explore the use ofsupervised sequence segmentation approaches to pinpointenhancer regions (HM-SVMs). The evolution ofbinding sites is another important aspect, we payattention to. Long-ranging interactions between differentgenomic loci are still enigmatic, yet are of tremendousimportance to gene regulation. We support thisimportant endeavor by an experimental design algorithmfor the chromatin conformation capture (3C)technique.Pristionchus – a model system in ecologyPristionchus pacificus has been established as a satellitesystem to Caenorhabditis elegans over the last years. P.pacificus is an omnivorous nematode and lives in anecromenic association with scarab beetles, which isthought to constitute an evolutionary intermediatebetween free living nematodes and true parasites. Tocomplement our biological knowledge, we sequencedthe P. pacificus genome and found it to be enriched forgene families involved in stress response and metabolismof xenobiotics. Additionally, there are severalinstances of lateral gene transfer. For example, cellulasegene predictions were confirmed by experiment andshown to be integrated into the host biology by activityassays. Another set of predicted protein-coding genesdid not show any similarity to the known protein universeand is currently being confirmed by transcriptomesequencing and mass spectrometry approaches.Genome evolution – content, order and variationPhylogenetic profiling of gene content may guide us instudying species adaptation to certain environments.Similarly, gene order is constrained by several partlyunknown factors. We invented algorithms for identifyinggene order conservation without assigning orthologya priori. We are able to look deep into the history ofgenome structure evolution since these approaches donot rely on a given whole-genome alignment. We arelikewise interested in reconstructing the order of theseevents (in collaboration with Jian Ma, UCSC). Sequencevariation (SNPs and Indels) is another layer of genome198 Berlin Institute of Medical Systems Biology