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- Editiertes Buch
- KonferenzbeitragIdentifying microRNAs and their targets(German conference on bioinformatics – GCB 2007, 2007) Rajewsky, NikolausI will summarize what can be learned from predicting and analyzing microRNA targets. As an example, I will discuss the function of miR-150 in the immune system. Finally, I will present a new algorithm for the identification of microRNAs from deep sequencing data.
- KonferenzbeitragInferring genomic footprints of adaptation from SNP data(German conference on bioinformatics – GCB 2007, 2007) Stephan, WolfgangAn important goal of population genetics is to determine the forces that have shaped the pattern of genetic variation in natural populations. For inferring the adaptive history of populations, we developed likelihood methods using the coalescent approach. We applied these techniques to Drosophila melanogaster, an originally African species that colonized temperate regions around the world after the last ice age. Our analyses suggest that the ancestral African population expanded its size about 60,000 years ago. The non-African populations split off from the African lineage about 16,000 years ago, thereby suffering severe population size bottlenecks. These demographic changes were accompanied by the fixation of numerous beneficial mutations, as revealed by signatures of positive directional selection in the genome (“selective sweeps”). The estimated rate of adaptive substitution is very high (in the order of one per genome per 100 generations). In several of the genomic regions exhibiting selective sweeps, we found genes with significant expression differences between African and non- African lines, suggesting that regulatory elements were the targets of selection and facilitated adaptation of fruit flies to temperate climates.
- KonferenzbeitragControl of translation: comparative genomics and mechanistic aspects(German conference on bioinformatics – GCB 2007, 2007) Pilpel, Yitzhak; Man, OrnaA major challenge in comparative genomics is to understand how phenotypic differences between species are encoded in their genomes. Phenotypic divergence may result from differential transcription of orthologous genes, yet less is known about the involvement of differential translation regulation in species phenotypic divergence. In order to assess translation effects on divergence, we analyzed approximately 2,800 orthologous genes in nine yeast genomes. For each gene in each species, we predicted translation efficiency, using a measure of the adaptation of its codons to the organism's tRNA pool. Mining this data set, we found hundreds of genes and gene modules with correlated patterns of translational efficiency across the species. One signal encompassed entire modules that are either needed for oxidative respiration or fermentation and are efficiently translated in aerobic or anaerobic species, respectively. In addition, the efficiency of translation of the mRNA splicing machinery strongly correlates with the number of introns in the various genomes. Altogether, we found extensive selection on synonymous codon usage that modulates translation according to gene function and organism phenotype. We conclude that, like factors such as transcription regulation, translation efficiency affects and is affected by the process of species divergence.
- KonferenzbeitragThe Third Rebuttal of the Random Breakage Theory(German conference on bioinformatics – GCB 2007, 2007) Pevzner, Pavel A.Rearrangements are genomic "earthquakes" that change the chromosomal architectures. The fundamental question in molecular evolution is whether there exist "chromosomal faults" where rearrangements are happening over and over again. In 1984 Nadeau and Taylor proposed the Random Breakage Model (RBM) of chromosome evolution that recently caused a controversy. RBM postulates that rearrangements are "random", and thus there is no rearrangement hot-spots in mammalian genomes. It became the de facto theory of chromosome evolution (due to its prophetic prediction power) but in 2003 was refuted by Pevzner and Tesler who gave a non-constructive argument against RBM using a combinatorial theorem. They further proposed the Fragile Breakage Model that postulates that mammalian genomes represent a mosaic of fragile and solid regions. However, the rebuttal of RBM caused a controversy and shortly after Pevzner-Tesler work was published, Sankoff and Trinh, 2004 gave a rebuttal of the rebuttal of RBM. Recently, Peng et al., 2006 re-examined the Sankoff-Trinh’s arguments and demonstrated that they fell victims to their inaccurate synteny block generation algorithm. Sankoff, 2006 recently acknowledged the flaw in Sankoff and Trinh, 2004 but argued that a larger set of rearrangement operations (e.g., transpositions) may explain the "fragile regions" phenomenon and that the "block deletion" argument in Sankoff and Trinh, 2004 is still valid. In this talk we give a rebuttal of the rebuttal (Sankoff, 2006) of the rebuttal (Peng et al., 2006) of the rebuttal (Sankoff and Trinh, 2004) of the rebuttal (Pevzner and Tesler, 2003) of RBM. We further describe the evidence from recent biological studies pointing to the specific fragile regions in the human genome.
- KonferenzbeitragIntegrative analysis of transcriptome and metabolome data(German conference on bioinformatics – GCB 2007, 2007) Willmitzer, Lothar; Caldana, Camila; Fernie, Alisdair; Giavalisco, Patrick; Hannah, Matthew; Redestig, Hennig; Steinhauser, DirkBiological systems have to react to environmental and/or developmental changes by adjusting their biochemical/cellular machinery on numerous levels. In many cases small molecules play a crucial role as signal molecules transmitting changes in state to receptor molecules which subsequently translate this into changes on various levels of the realization of genomic information. We here start out from the hypothesis that in most biological systems there are many more small molecules which also serve a signalling function than generally acknowledged. This hypothesis is based on three simple arguments, which present limitations in classical approaches to detect signalling molecules: - In order to identify a signalling molecule one has to be able to monitor the response of the system under study towards this signal, - In order to identify a signalling molecule one has to be able to detect and quantify this molecule, - A third important point to consider is the fact that in many cases test for signalling molecules were performed by externally applying the putative signal molecule to the system. It is obvious that further problem linked to uptake and mobility of the compound arise during this approach. We therefore set out to design an experiment where we tried to largely overcome these three limitations. As to the response of the system we decided to use the transcriptional response as a read- out. As to the second and third limitation, we decided to rather monitor endogenous changes of small molecules. To this end we applied metabolomics techniques for analysing the state of a system which at least in an ideal world should allow the quantification and identification of all small molecules present in the biological system. We here present a first set of data resulting from a large experiment where the response of a plant system (leaves of Arabidopsis thaliana) as a function of numerous environmental conditions applied has been followed in parallel on both analytic levels described above, i.e. RNA expression and metabolite profiles.
- Editiertes Buch
- KonferenzbeitragAre we overestimating the number of cell-cycling genes? The impact of background models for time series data(German conference on bioinformatics – GCB 2007, 2007) Futschik, Matthias E.; Herzel, HanspeterPeriodic processes play fundamental roles in organisms. Prominent examples are the cell cycle and the circadian clock. Microarray array technology has enabled us to screen complete sets of transcripts for possible association with such fundamental periodic processes on a system-wide level. Frequently, quite a large number of genes has been detected as periodically expressed. However, the small overlap of identified genes between different studies has shaded considerable doubts about the reliability of the detected periodic expression. In this study, we show that a major reason for the lacking agreement is the use of an inadequate background model for the determination of significance. We demonstrate that the choice of background model has considerable impact on the statistical significance of periodic expression. For illustration, we reanalyzed two microarray studies of the yeast cell cycle. Our evaluation strongly indicates that the results of previous analyses might have been overoptimistic and that the use of more suitable background model promises to give more realistic results.
- Editiertes BuchSoftware Engineering 2014(2014)