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ACCUSA - Accurate SNP calling on draft genomes manuscript accepted
Next generation sequencing technologies facilitate genome-wide analysis of several biological processes. We are interested in whole-genome genotyping. To our knowledge, none of the existing SNP callers consider the quality of the reference genome, which is not necessary for high quality assemblies of well-studied model organisms. However, most genome projects will remain in draft status with little to no genome assembly improvement due to time and financial constraints. Here we present a simple yet elegant solution ('ACCUSA'), which considers both, the read qualities as well as the reference genome's quality using a Bayesian framework. We demonstrate that ACCUSA is as good as current SNP calling software in detecting true SNPs. More important, ACCUSA does not call spurious SNPs, which originate from a poor reference sequence.
ACCUSA2: Multi-purpose SNV calling enhanced by probabilistic integration of quality scores - online
ACCUSA2: Multi-purpose SNV calling enhanced by probabilistic integration of quality scores Michael Piechotta; Christoph Dieterich Bioinformatics 2013; doi: 10.1093/bioinformatics/btt268
Active turnover modulates mature microRNA activity in Caenorhabditis elegans
MicroRNAs (miRNAs) constitute a large class of regulatory RNAs that repress target messenger RNAs to control various biological processes1. Accordingly, miRNA biogenesis is highly regulated, controlled at both transcriptional and post-transcriptional levels2, and overexpression and underexpression of miRNAs are linked to various human diseases, particularly cancers1, 3. As RNA concentrations are generally a function of biogenesis and turnover, active miRNA degradation might also modulate miRNA accumulation, and the plant 3'right arrow5' exonuclease SDN1 has been implicated in miRNA turnover4. Here we report that degradation of mature miRNAs in the nematode Caenorhabditis elegans, mediated by the 5'right arrow3' exoribonuclease XRN-2, affects functional miRNA homeostasis in vivo. We recapitulate XRN-2-dependent miRNA turnover in larval lysates, where processing of precursor-miRNA (pre-miRNA) by Dicer, unannealing of the miRNA duplex and loading of the mature miRNA into the Argonaute protein of the miRNA-induced silencing complex (miRISC) are coupled processes that precede degradation of the mature miRNA. Although Argonaute:miRNA complexes are highly resistant to salt, larval lysate promotes efficient release of the miRNA, exposing it to degradation by XRN-2. Release and degradation can both be blocked by the addition of miRNA target RNA. Our results therefore suggest the presence of an additional layer of regulation of animal miRNA activity that might be important for rapid changes of miRNA expression profiles during developmental transitions and for the maintenance of steady-state concentrations of miRNAs. This pathway might represent a potential target for therapeutic intervention on miRNA expression.
Andreas Kuntzagk says GoodBye
After 11.5 years at MDC Andreas Kuntzagk leaves.
Chromosome conformation capture primer design
Our paper "Rapid design of optimal primers for chromosome conformation capture assays" by Fröhler and Dieterich was accepted for publication in BMC Genomics.
Cluster relocation
Upcoming relocation of the compute cluster and all servers starting june 15th 2012.
Conserved miRNAs are candidate post-transcriptional regulators of developmental arrest in free-living and parasitic nematodes
Our article on miRNA evolution in free-living and parasitic nematodes appeared online.
CYNTENATOR manuscript accepted
CYNTENATOR: Progressive gene order alignment of 17 vertebrate genomes
De novo assembly and validation of planaria transcriptome by massive parallel sequencing and shotgun proteomics
Adamidi C, Wang Y, Gruen D, Mastrobuoni G, You X, Tolle D, Dodt M, Mackowiak SD, Gogol-Doering A, Oenal P, Rybak A, Ross E, Alvarado AS, Kempa S, Dieterich C, Rajewsky N, Chen W. Max-Delbrück-Center for Molecular Medicine, Berlin Institute for Medical Systems Biology, Robert Rössle Straße 10, Berlin 13125, Germany;
Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.
Dauers differ more than expected. A transcriptome study of C. elegans and P. pacificus has all the details: http://www.ncbi.nlm.nih.gov/pubmed/22712530
doRiNA: a database of RNA interactions in post-transcriptional regulation
The doRiNA database was published online in NAR on 15 Nov 2012 and will be part of the database issue 2012
doRiNA is featured on systembiologie.de
The BIMSB database of post-transcriptional regulatory elements is featured in volume 05 of the German magazine "systembiologie.de" (http://www.systembiologie.de/en/magazine.html). The doRiNA database can be accessed via http://dorina.mdc-berlin.de
FLEXBAR is accepted for publication
FLEXBAR—Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms is accepted for publication in the special issue "Next Generation Sequencing Approaches in Biology" of MDPI Biology.
Helicos BioSciences Announces the First Ever Single-Molecule View of Whole Human Genome
Study Performed at Stanford University Published in Nature Biotechnology.
Our Review is published - Computational biology of RNA interactions
The biodiversity of the RNA world has been underestimated for decades. RNA molecules are key building blocks, sensors, and regulators of modern cells. The biological function of RNA molecules cannot be separated from their ability to bind to and interact with a wide space of chemical species, including small molecules, nucleic acids, and proteins. Computational chemists, physicists, and biologists have developed a rich tool set for modeling and predicting RNA interactions. These interactions are to some extent determined by the binding conformation of the RNA molecule. RNA binding conformations are approximated with often acceptable accuracy by sequence and secondary structure motifs. Secondary structure ensembles of a given RNA molecule can be efficiently computed in many relevant situations by employing a standard energy model for base pair interactions and dynamic programming techniques. The case of bi-molecular RNA-RNA interactions can be seen as an extension of this approach. However, unbiased transcriptome-wide scans for local RNA-RNA interactions are computationally challenging yet become efficient if the binding motif/mode is known and other external information can be used to confine the search space. Computational methods are less developed for proteins and small molecules, which bind to RNA with very high specificity. Binding descriptors of proteins are usually determined by in vitro high-throughput assays (e.g., microarrays or sequencing). Intriguingly, recent experimental advances, which are mostly based on light-induced cross-linking of binding partners, render in vivo binding patterns accessible yet require new computational methods for careful data interpretation. The grand challenge is to model the in vivo situation where a complex interplay of RNA binders competes for the same target RNA molecule. Evidently, bioinformaticians are just catching up with the impressive pace of these developments. WIREs RNA 2013, 4:107-120. doi: 10.1002/wrna.1147
Pristionchus pacificus daf-16/FOXO is Essential for Dauer Formation but Dispensable for Mouth Form Dimorphism
Akira Ogawa, Gilberto Bento, Gabi Bartelmes, Christoph Dieterich, and Ralf J Sommer
Proteogenomics of Pristionchus pacificus manuscript accepted
the manuscript will appear in Genome Research
The mRNA-Bound Proteome and Its Global Occupancy Profile on Protein-Coding Transcripts
Our work on transcriptome-wide RNA-protein binding was published http://www.ncbi.nlm.nih.gov/pubmed/22681889
