Minimotif Miner (MnM) consists of a minimotif database and a web-based application that enables prediction of motif-based functions in user-supplied protein queries. We have revised MnM by expanding the database more than 10-fold to approximately 5000 motifs and standardized the motif function definitions. The web-application user interface has been redeveloped with new features including improved navigation, screencast-driven help, support for alias names and expanded SNP analysis. A sample analysis of prion shows how MnM 2 can be used. Weblink: http://mnm.engr.uconn.edu, weblink for version 1 is http://sms.engr.uconn.edu.
BackgroundOne of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of related data elements. With these two purposes in mind, the authors provide a proposed syntax for minimotif semantics primarily useful for functional annotation.ResultsHerein, we present a structured syntax of minimotifs and their functional annotation. A syntax-based model of minimotif function with established minimotif sequence definitions was implemented using a relational database management system (RDBMS). To assess the usefulness of our standardized semantics, a series of database queries and stored procedures were used to classify SH3 domain binding minimotifs into 10 groups spanning 700 unique binding sequences.ConclusionOur derived minimotif syntax is currently being used to normalize minimotif covalent chemistry and functional definitions within the MnM database. Analysis of SH3 binding minimotif data spanning many different studies within our database reveals unique attributes and frequencies which can be used to classify different types of binding minimotifs. Implementation of the syntax in the relational database enables the application of many different analysis protocols of minimotif data and is an important tool that will help to better understand specificity of minimotif-driven molecular interactions with proteins.
Protein-protein interactions are important to understanding cell functions; however our theoretical understanding is limited. There is a general discontinuity between the well-accepted physical and chemical forces that drive protein-protein interactions and the large collections of identified protein-protein interactions in various databases. Minimotifs are short functional peptide sequences that provide a basis to bridge this gap in knowledge. However, there is no systematic way to study minimotifs in the context of protein-protein interactions or vice versa. Here we have engineered a set of algorithms that can be used to identify minimotifs in known protein-protein interactions and implemented this for use by scientists in Minimotif Miner. By globally testing these algorithms on verified data and on 100 individual proteins as test cases, we demonstrate the utility of these new computation tools. This tool also can be used to reduce false positive predictions in the discovery of novel minimotifs. The statistical significance of these algorithms is demonstrated by an ROC analysis (p = 0.001).
␥-Type small, acid-soluble spore proteins (SASP) are the most abundant proteins in spores of at least some members of the bacterial order Bacillales, yet they remain an enigma from both functional and phylogenetic perspectives. Current work has shown that the ␥-type SASP or their coding genes (sspE genes) are present in most spore-forming members of Bacillales, including at least some members of the Paenibacillus genus, although they are apparently absent from Clostridiales species. We have applied a new method of searching for sspE genes, which now appear to also be absent from a clade of Bacillales species that includes Alicyclobacillus acidocaldarius and Bacillus tusciae. In addition, no ␥-type SASP were found in A. acidocaldarius spores, although several of the DNA-binding ␣/-type SASP were present. These findings have elucidated the phylogenetic origin of the sspE gene, and this may help in determining the precise function of ␥-type SASP.Bacterial spores of species of the Firmicutes phylum contain a number of small, acid-soluble proteins (SASP) that comprise 10 to 15% of the protein in the spore's central region or core (30, 32). The following two types of major SASP have been identified in spores: (i) ␣/-type SASP that are products of a multi-ssp gene family and have extremely similar sequences both within and across species and (ii) ␥-type SASP that are almost always encoded by a single sspE gene; this is the most abundant protein found in spores of a number of species and comprises 5 to 8% of total spore protein (18-20, 29-32, 39). In contrast to the highly conserved sequences of ␣/-type SASP, sequences of ␥-type SASP are not well conserved across species, and this has allowed the use of sspE and SASP-␥ sequences to distinguish closely related Bacillus strains and species (17).In Bacillus subtilis, genes encoding both ␣/-type and ␥-type SASP are transcribed in parallel late in spore development when the various SASP are synthesized, and the transcription of ssp genes is mediated by the RNA polymerase sigma factor, G (22). The SASP are degraded soon after spores complete the germination process and begin outgrowth, and one function of these proteins is to serve as a reservoir of amino acids (aa) for protein synthesis early in outgrowth (12,30,32). The latter is an important function, since spores become deficient in a number of amino acid biosynthetic enzymes during spore formation and synthesize these enzymes only during spore outgrowth. In addition to serving as a reservoir of amino acids, the ␣/-type SASP have an additional function, as these proteins saturate spore DNA and protect it from many types of damage and are thus very important for long-term spore survival (30-32). However, other than serving as an amino acid reservoir, no additional function has been demonstrated for ␥-type SASP (12, 30, 32).In the current work, we have examined genome sequence information for spore-forming Firmicutes and have confirmed that (i) spore-forming Clostridiales species appear to lack sspE genes; (ii) most bu...
We recently reported that CCT chaperonin subunits are upregulated in a cardiac-specific manner under time-restricted feeding (TRF) (Gill et al. Science 2015, 347:1265–9), suggesting that TRiC/CCT has a heart-specific function. To understand the CCT chaperonin function in cardiomyocytes, we performed its cardiac-specific knock-down in the Drosophila melanogaster model. This resulted in disorganization of cardiac actin- and myosin-containing myofibrils and severe physiological dysfunction, including restricted heart diameters, elevated cardiac dysrhythmia and compromised cardiac performance. We also noted that cardiac-specific knock-down of CCT chaperonin significantly shortens lifespans. Additionally, disruption of circadian rhythm yields further deterioration of cardiac function of hypomorphic CCT mutants. Our analysis reveals that both the orchestration of protein folding and circadian rhythms mediated by CCT chaperonin are critical for maintaining heart contractility.
NMR spectroscopists are hindered by the lack of standardization for spectral data among the file formats for various NMR data processing tools. This lack of standardization is cumbersome as researchers must perform their own file conversion in order to switch between processing tools and also restricts the combination of tools employed if no conversion option is available. The CONNJUR Spectrum Translator introduces a new, extensible architecture for spectrum translation and introduces two key algorithmic improvements. This first is translation of NMR spectral data (time and frequency domain) to a single in-memory data model to allow addition of new file formats with two converter modules, a reader and a writer, instead of writing a separate converter to each existing format. Secondly, the use of layout descriptors allows a single fid data translation engine to be used for all formats. For the end user, sophisticated metadata readers allow conversion of the majority of files with minimum user configuration. The open source code is freely available at http://connjur.sourceforge.net for inspection and extension.Electronic supplementary materialThe online version of this article (doi:10.1007/s10858-011-9497-1) contains supplementary material, which is available to authorized users.
Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid and convenient than current approaches using isolated repositories. Several new hypotheses for integrase were created as an example, and we experimentally confirmed a predicted CK2 phosphorylation site. Weblink: [http://hivtoolbox.bio-toolkit.com]
CONNJUR Workflow Builder (WB) is an open-source software integration environment that leverages existing spectral reconstruction tools to create a synergistic, coherent platform for converting biomolecular NMR data from the time domain to the frequency domain. WB provides data integration of primary data and metadata using a relational database, and includes a library of pre-built workflows for processing time domain data. WB simplifies maximum entropy reconstruction, facilitating the processing of non-uniformly sampled time domain data. As will be shown in the paper, the unique features of WB provide it with novel abilities to enhance the quality, accuracy, and fidelity of the spectral reconstruction process. WB also provides features which promote collaboration, education, parameterization, and non-uniform data sets along with processing integrated with the Rowland NMR Toolkit (RNMRTK) and NMRPipe software packages. WB is available free of charge in perpetuity, dual-licensed under the MIT and GPL open source licenses.
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