Comprehensive analysis of pseudogenes in prokaryotes: widespread gene decay and failure of putative horizontally transferred genes

Background  

Pseudogenes often manifest themselves as disabled copies of known genes. In prokaryotes, it was generally believed (with a few well-known exceptions) that they were rare.     

MolMovDB: analysis and visualization of conformational change and structural flexibility

The Database of Macromolecular Movements (http://MolMovDB.org) is a collection of data and software pertaining to flexibility in protein and RNA structures. The database is organized into two parts. Firstly, a collection of 'morphs' of solved structures representing different states of a molecule provides quantitative data for flexibility and a number of graphical representations. Secondly, a classification of known motions according to type of conformational change (e.g. 'hinged domain' or 'allosteric') incorporates textual annotation and information from the literature relating to the motion, linking together many of the morphs. A variety of subsets of the morphs are being developed for use in statistical analyses. In particular, for each subset it is possible to derive distributions of various motional quantities (e.g. maximum rotation) that can be used to place a specific motion in context as being typical or atypical for a given population. Over the past year, the database has been greatly expanded and enhanced to incorporate new structures and to improve the quality of data. The 'morph server', which enables users of the database to add new morphs either from their own research or the PDB, has also been enhanced to handle nucleic acid structures and multi-chain complexes.     

Strategies for structural proteomics of prokaryotes: Quantifying the advantages of studying orthologous proteins and of using both NMR and X-ray crystallography approaches

Only about half of non-membrane-bound proteins encoded by either bacterial or archaeal genomes are soluble when expressed in Escherichia coli (Yee et al., Proc Natl Acad Sci USA 2002;99:1825-1830; Christendat et al., Prog Biophys Mol Biol 200;73:339-345). This property limits genome-scale functional and structural proteomics studies, which depend on having a recombinant, soluble version of each protein. An emerging strategy to increase the probability of deriving a soluble derivative of a protein is to study different sequence homologues of the same protein, including representatives from thermophilic organisms, based on the assumption that the stability of these proteins will facilitate structural analysis. To estimate the relative merits of this strategy, we compared the recombinant expression, solubility, and suitability for structural analysis by NMR and/or X-ray crystallography for 68 pairs of homologous proteins from E. coli and Thermotoga maritima. A sample suitable for structural studies was obtained for 62 of the 68 pairs of homologs under standardized growth and purification procedures. Fourteen (eight E. coli and six T. maritima proteins) samples generated NMR spectra of a quality suitable for structure determination and 30 (14 E. coli and 16 T. maritima proteins) samples formed crystals. Only three (one E. coli and two T. maritima proteins) samples both crystallized and had excellent NMR properties. The conclusions from this work are: (1) The inclusion of even a single ortholog of a target protein increases the number of samples for structural studies almost twofold; (2) there was no clear advantage to the use of thermophilic proteins to generate samples for structural studies; and (3) for the small proteins analyzed here, the use of both NMR and crystallography approaches almost doubled the number of samples for structural studies.     

Recordings,behaviour and models related to corticothalamic feedback

In this paper, we review recent work on aspects of corticothalamic interactions in the auditory and in the visual systems. There are gross similarities in the arrangements of these systems, but considerable contrasts in the processing computations and in the effects of corticothalamic feedback.     

The dominance of the population by a selected few: power-law behaviour applies to a wide variety of genomic properties

Background  

The sequencing of genomes provides us with an inventory of the 'molecular parts' in nature, such as protein families and folds, and their functions in living organisms. Through the analysis of such inventories, it has been shown that different genomes have very different usage of parts; for example, the common folds in the worm are very different from those in Escherichia coli.     

Integration of genomic datasets to predict protein complexes in yeast

The ultimate goal of functional genomics is to define the function of all the genes in the genome of an organism. A large body of information of the biological roles of genes has been accumulated and aggregated in the past decades of research, both from traditional experiments detailing the role of individual genes and proteins, and from newer experimental strategies that aim to characterize gene function on a genomic scale.It is clear that the goal of functional genomics can only be achieved by integrating information and data sources from the variety of these different experiments. Integration of different data is thus an important challenge for bioinformatics.The integration of different data sources often helps to uncover non-obvious relationships between genes, but there are also two further benefits. First, it is likely that whenever information from multiple independent sources agrees, it should be more valid and reliable. Secondly, by looking at the union of multiple sources, one can cover larger parts of the genome. This is obvious for integrating results from multiple single gene or protein experiments, but also necessary for many of the results from genome-wide experiments since they are often confined to certain (although sizable) subsets of the genome.In this paper, we explore an example of such a data integration procedure. We focus on the prediction of membership in protein complexes for individual genes. For this, we recruit six different data sources that include expression profiles, interaction data, essentiality and localization information. Each of these data sources individually contains some weakly predictive information with respect to protein complexes, but we show how this prediction can be improved by combining all of them. Supplementary information is available at http://bioinfo.mbb.yale.edu/integrate/interactions/.Abbreviations: TP: true possitive; TN: true negative; FP: false positive; FN: false negative; Y2H: yeast two-hybrid.     

Calculations of protein volumes: sensitivity analysis and parameter database

MOTIVATION: The precise sizes of protein atoms in terms of occupied packing volume are of great importance. We have previously presented standard volumes for protein residues based on calculations with Voronoi-like polyhedra. To understand the applicability and limitations of our set, we investigated, in detail, the sensitivity of the volume calculations to a number of factors: (i) the van der Waals radii set, (ii) the criteria for including buried atoms in the calculations or atom selection, (iii) the method of positioning the dividing plane in polyhedra construction, and (iv) the set of structures used in the averaging. RESULTS: We find that different radii sets have only moderate affects to the distribution and mean of volumes. Atom selection and dividing plane methods cause larger changes in protein atoms volumes. More significantly, we show how the variation in volumes appears to be clearly related to the quality of the structures analyzed, with higher quality structures giving consistently smaller average volumes with less variance.