The Bioinformatics / Systems Biology group (BSB) studies the dynamics of entire biological systems, both at evolutionary time scales and also at time scales down to a few minutes. The BSB group works principally, in close collaborations with laboratory scientists, on the computational aspects of studying such systems, in fields ranging from genetics to genomics to proteomics. The focus in the collaborative studies is on the downstream statistical analysis and comparative modelling in order to extract the maximum information from a given experiment.
Recent technological developments have dramatically increased the cost-effectiveness and speed of measurements in molecular biology, to the extent that many biological endeavours are now “data-driven”. For example, massively parallel next-generation nucleotide sequencing can now be used to characterize polymorphisms, population structures, and entire transcriptomes. Even in routine experiments such as chromatin immunoprecipitation, sequencing is beginning to replace microarray technology. This increased availability of sequence information is opening up entirely new avenues for the study of gene function and gene evolution, potentially revealing the origins of molecular and functional diversity, and the principles of microbial ecology. Researchers are now beginning to move sequencing technology out of the laboratories and into the environment, sampling anything from the organisms found on deep-sea hydrothermal vents to the dental plaque on human teeth. Similarly, proteomics technology is now also rapidly gaining momentum, becoming the technology of choice for system-wide quantifications of proteins and their modifications. For the first time, this allows researchers to model (and measure) entire pathways or functional subsystems in the cell.
Projects and Services
Phylogenetic assignment of partial genome sequences
The sequencing of complex environmental microbial communities often produces numerous sequence fragments that cannot easily be traced to their cellular origin. To assign partial sequences from these unknown species to their correct taxonomic classification, the BSB group develops algorithms and maintains essential reference information. Because of data limitations, emphasis is placed on providing error estimates and validation so that researchers can judge the relevance and the limits of the assignments. From published environmental sequence datasets, and from sequences obtained through collaborations, a global repository of taxonomically classified environmental communities is created and maintained.
Evolution of habitats and communities
In addition to a taxonomic assessment, environmental sequence data also need to be classified in functional terms and correlated to community ecology. For this, the BSB group develops procedures and databases that provide a consistent functional annotation of the sequences, and assigns the open reading frames into hierarchical pathways and functional classes.
By comparing independent environmental samples with one another, and by correlating their functional annotations to taxonomic assignments, the research aim is to exhaustively map functional capabilities onto the phylogenetic tree of life. This should reveal where and when certain phenotypes first developed, how they have been transferred between individual lineages, and what environments are the most promising to isolate a certain class of genes.
The STRING database: genomes and interaction networks for systems biology
Genome sequences provide essential background information for the interpretation of modern molecular biology data, for example for high-throughput techniques such as proteomics or transcriptomics. The STRING database (“Search Tool for the Retrieval of Interacting Genes”) provides this background information to researchers. STRING is a regularly updated collection of completely sequenced genomes, augmented with comprehensive data on pathways and interactomes. The resource collects functional and structural annotations for the proteins encoded in each genome, and provides consistently assembled and scored network information on all known interactions between them. Networks can be easily navigated, exported in a variety of formats, and extended with additional functional genomics data depending on the desired application. The BSB group has been developing and maintaining STRING in collaboration with researchers at EMBL since 2003.
Websites for Further Information
Bioinformatics / Systems Biology Group: http://www.imls.uzh.ch/research/vonmering.html
STRING database: http://www.string-db.org/