From Large Scale Rearrangements to Mode Coupling Phenomenology

We consider the equilibrium dynamics of Ising spin models with multi-spin interactions on sparse random graphs (Bethe lattices). Such models undergo a mean field glass transition upon increasing the graph connectivity or lowering the temperature. Focusing on the low temperature limit, we identify the large scale rearrangements responsible for the dynamical slowing-down near the transition. We are able to characterize exactly the dynamics near criticality by analyzing the statistical properties of such rearrangements. Our approach can be generalized to a large variety of glassy models on sparse random graphs, ranging from satisfiability to kinetically constrained models.Comment: 4 pages, 4 figures, minor corrections, accepted versio

NOXclass: prediction of protein-protein interaction types

BACKGROUND: Structural models determined by X-ray crystallography play a central role in understanding protein-protein interactions at the molecular level. Interpretation of these models requires the distinction between non-specific crystal packing contacts and biologically relevant interactions. This has been investigated previously and classification approaches have been proposed. However, less attention has been devoted to distinguishing different types of biological interactions. These interactions are classified as obligate and non-obligate according to the effect of the complex formation on the stability of the protomers. So far no automatic classification methods for distinguishing obligate, non-obligate and crystal packing interactions have been made available. RESULTS: Six interface properties have been investigated on a dataset of 243 protein interactions. The six properties have been combined using a support vector machine algorithm, resulting in NOXclass, a classifier for distinguishing obligate, non-obligate and crystal packing interactions. We achieve an accuracy of 91.8% for the classification of these three types of interactions using a leave-one-out cross-validation procedure. CONCLUSION: NOXclass allows the interpretation and analysis of protein quaternary structures. In particular, it generates testable hypotheses regarding the nature of protein-protein interactions, when experimental results are not available. We expect this server will benefit the users of protein structural models, as well as protein crystallographers and NMR spectroscopists. A web server based on the method and the datasets used in this study are available at

An algebra for feature-oriented software development

Feature-Oriented Software Development (FOSD) provides a multitude of formalisms, methods, languages, and tools for building variable, customizable, and extensible software. Along different lines of research different ideas of what a feature is have been developed. Although the existing approaches have similar goals, their representations and formalizations have not been integrated so far into a common framework. We present a feature algebra as a foundation of FOSD. The algebra captures the key ideas and provides a common ground for current and future research in this field, in which also alternative options can be explored

A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse

GOTax: investigating biological processes and biochemical activities along the taxonomic tree

GOTax, a novel web-based platform that integrates protein annotation with protein family classification and taxonomy, allows for an extensive assessment of functional similarity between proteins and for comparing and analyzing the distribution of protein families and protein functions over different taxonomic groups

J Mol Biol

Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by a trinucleotide expansion in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2 (ATX2), whose cellular function is unknown. However, ATX2 interacts with A2BP1, a protein containing an RNA-recognition motif, and the existence of an interaction motif for the C-terminal domain of the poly(A)-binding protein (PABC) as well as an Lsm (Like Sm) domain in ATX2 suggest that ATX2 like its yeast homolog Pbp1 might be involved in RNA metabolism. Here, we show that, similar to Pbp1, ATX2 suppresses the petite (pet−) phenotype of Δmrs2 yeast strains lacking mitochondrial group II introns. This finding points to a close functional relationship between the two homologs. To gain insight into potential functions of ATX2, we also generated a comprehensive protein interaction network for Pbp1 from publicly available databases, which implicates Pbp1 in diverse RNA-processing pathways. The functional relationship of ATX2 and Pbp1 is further corroborated by the experimental confirmation of the predicted interaction of ATX2 with the cytoplasmic poly(A)-binding protein 1 (PABP) using yeast-2-hybrid analysis as well as co-immunoprecipitation experiments. Immunofluorescence studies revealed that ATX2 and PABP co-localize in mammalian cells, remarkably, even under conditions in which PABP accumulates in distinct cytoplasmic foci representing sites of mRNA triage

Applications of semantic similarity measures

There has been much interest in uncovering protein-protein interactions and their underlying domain-domain interactions. Many experimental techniques have been developed, for example yeast-two-hybrid screening and tandem affinity purification. Since it is time consuming and expensive to perform exhaustive experimental screens, in silico methods are used for predicting interactions. However, all experimental and computational methods have considerable false positive and false negative rates. Therefore, it is necessary to validate experimentally determined and predicted interactions. One possibility for the validation of interactions is the comparison of the functions of the proteins or domains. Gene Ontology (GO) is widely accepted as a standard vocabulary for functional terms, and is used for annotating proteins and protein families with biological processes and their molecular functions. This annotation can be used for a functional comparison of interacting proteins or domains using semantic similarity measures. Another application of semantic similarity measures is the prioritization of disease genes. It is know that functionally similar proteins are often involved in the same or similar diseases. Therefore, functional similarity is used for predicting disease associations of proteins. In the first part of my talk, I will introduce some semantic and functional similarity measures that can be used for comparison of GO terms and proteins or protein families. Then, I will show their application for determining a confidence threshold for domain-domain interaction predictions. Additionally, I will present FunSimMat (http://www.funsimmat.de/), a comprehensive resource of functional similarity values available on the web. In the last part, I will introduce the problem of comparing diseases, and a first attempt to apply functional similarity measures based on GO to this problem

P35. Intratumoral patterns of clonal evolution in meningiomas

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