P115 - GCB 2007 - German Conference on Bioinformatics 2007
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- KonferenzbeitragRevealing comprehensive genotype–phenotype associations through logic relationships(German conference on bioinformatics – GCB 2007, 2007) Antonov, Alexey V.; Mewes, Hans W.A novel approach which employs principles of higher order logic analyses was developed to systematically correlate phylogenetic data with phenotype profiles by identification of phenotype specific patterns of presence of multiple proteins. For example, for most genomes expressing trait A, the presence of protein C presumes the presence of protein B, while for other genomes (not expressing the trait) the presence of protein C presumes the absence of protein B. We demonstrate that the phenotype specific patterns reflect fundamental structural changes in the genotype of microorganisms in relation to conditions provided by presence/absence of a trait. We discover many previously unidentified genotype–phenotype associations on the level of fundamental biochemical processes.
- 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.
- KonferenzbeitragFinding relevant biotransformation routes in weighted metabolic networks using atom mapping rules(German conference on bioinformatics – GCB 2007, 2007) Blum, Torsten; Kohlbacher, OliverComputational analysis of pathways in metabolic networks has numerous applications in systems biology. While graph theory-based approaches have been pre- sented that find biotransformation routes from one metabolite to another in these net- works, most of these approaches suffer from finding too many routes, most of which are biologically infeasible or meaningless. We present a novel approach for finding relevant routes based on atom mapping rules (describing which educt atoms are mapped onto which product atoms in a chemical reaction). This leads to a reformulation of the problem as a lightest path search in a degree-weighted metabolic network. A key component of the approach is a new method of computing optimal atom mapping rules.
- KonferenzbeitragQVADIS: A package to compute proton transfer pathways in proteins(German conference on bioinformatics – GCB 2007, 2007) Kunz, Kerstin; Helms, VolkhardProton transfer reactions play an important role in many areas of biology. We reimplemented a method introduced by Taraphder et al. to characterize putative proton transfer pathways in proteins along hydrogen bonded networks and could re- trace their results on cytochrome P450cam. By combining this method with our established Q-HOP approach to compute proton transfer probabilities we present here to our best knowledge for the first time a general program package to characterize proton transfer pathways in biomolecules accounting for both side chain flexibility and transfer kinetics.
- KonferenzbeitragRNAplex: a fast and flexible RNA-RNA interaction search tool(German conference on bioinformatics – GCB 2007, 2007) Tafer, Hakim; Hofacker, Ivo L.Regulatory RNAs often unfold their action via RNA-RNA interaction. Transcriptional gene silencing by means of siRNAs and miRNA as well as snoRNA directed RNA editing rely on this mechanism. ncRNA regulation in bacteria is mainly based upon RNA duplex formation. Finding putative target sites for newly discovered ncR-NAs is a lengthy task as tools for cofolding RNA molecules like RNAcofold and RNAup have a run time proportional to O((n + m)3) which makes them unpractical for whole genome search. We present a new program, RNAplex, especially designed to quickly find possible hybridization sites for a query RNA in large RNA databases. In contrast to earlier approaches, RNAplex uses a slightly different energy model which reduces the computational time by a factor 65 compared to RNAhybrid without loss of sensitivity.
- KonferenzbeitragA general paradigm for fast, adaptive clustering of biological sequences(German conference on bioinformatics – GCB 2007, 2007) Reinert, Knut; Bauer, Markus; Döring, Andreas; Klau, Gunnar W.; Halpern, Aaron L.There are numerous methods that compute clusterings of biological sequences based on pairwise distances. This necessitates the computation of O(n2) sequence comparisons. Users usually want to apply the most sensitive distance measure which normally is the most expensive in terms of runtime. This poses a problem if the number of sequences is large or the computation of the measure is slow. In this paper we present a general heuristic to speed up distance based clustering methods considerably while compromising little on the accuracy of the results. The speedup comes from using fast comparison methods to perform an initial ‘top-down’ split into relatively homogeneous clusters, while the slower measures are used for smaller groups. Then profiles are computed for the final groups and the resulting profiles are used in a bottom-up phase to compute the final clustering. The algorithm is general in the sense that any sequence comparison method can be employed (e.g. for DNA, RNA or amino acids). We test our algorithm using a prototypical imple- mentation for agglomerative RNA clustering and show its effectiveness.
- KonferenzbeitragHigh-Precision Function Prediction using Conserved Interactions(German conference on bioinformatics – GCB 2007, 2007) Jaeger, S.; Leser, U.The recent availability of large data sets of protein- protein-interactions (PPIs) from various species offers new opportunities for functional genomics and proteomics. We describe a method for exploiting conserved and connected subgraphs (CCSs) in the PPI networks of multiple species for the prediction of protein function. Structural conservation is combined with functional conservation using a GeneOntology-based scoring scheme. We applied our method to the PPI networks of five species, i.e., E. coli, D. melanogaster, M. musculus, H. sapiens and S. cerevisiae. We detected surprisingly large CCSs for groups of thee species but not beyond. A manual analysis of the biological coherence of exemplary subgraphs strongly supports a close relationship between structural and functional conservation. Based on this observation, we devised an algorithm for function prediction based on CCS. Using our method, for instance, we predict new functional annotations for human based on mouse proteins with a precision of 70%.
- 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.
- KonferenzbeitragProtein structure comparison based on fold evolution(German conference on bioinformatics – GCB 2007, 2007) Kurbatova, Natalja; Mančinska, Laura; Vīksna, JurisThe paper presents a protein structure comparison algorithm that is capable to identify specific fold mutations between two proteins. The search for such mutations is based on structure evolution models suggesting that, similarly as sequences, protein folds (at least partially) evolve by a stepwise process, where each step comprises comparatively simple changes affecting few secondary structure elements. The particular fold mutations considered in this study are based on the work by Grishin [Gr01]. The algorithm uses structure representation by 3D graphs and is a modification of a method used in SSM structure alignment tool [KH04a]. Experiments demonstrate that our method is able automatically identify 85% of examples of fold mutations given by Grishin. Also a number of tests involving all-against-all comparisons of CATH struc- tural domains have been performed in order to measure comparative frequencies of different types of fold mutations and some statistical estimations have been obtained.
- KonferenzbeitragA Study on the Empirical Support for Prior Distributions on Phylogenetic Tree Topologies(German conference on bioinformatics – GCB 2007, 2007) Himmelmann, Lin M.; Metzler, DirkThere are several models for the evolutionary process forming a species tree. We examine the Birth-and-Death model (BDM), the Proportional-to-Distinguishable Arrangements (PDA) model, the Kirkpatrick and Slatkin (KS) model, the Beta-Splitting (BS) model and a model where birth rates evolve according to a Geometric Brownian Motion Process (GBM). For testing and calibrating the models, we evaluate tree topologies from TreeBASE and a large tree provided by the Tree of Life project. In a simulation we compare the distribution of tree topologies generated by the models with tree topologies of observed trees. For describing the distribution of topologies we use the tree imbalance statistics B1, Colless’C and Shao and Sokal’s N, and calculate the maximum-likelihood estimate of β from the BS model. Further we explore the splitting pattern of the generated trees. From the observed trees we show that trees generated by the BDM are too balanced and trees generated by the PDA model are too imbalanced. The BS model with β = −1, the KS model with ratio 1 : 2 and an adjusted GBM model represent better fitted models for reproducing the imbalance in observed tree topologies.