GDPC: connecting researchers with multiple integrated data sources

The goal of this project is to simplify access to genomic diversity and phenotype data, thereby encouraging reuse of this data. The Genomic Diversity and Phenotype Connection (GDPC) accomplishes this by retrieving data from one or more data sources and by allowing researchers to analyze integrated data in a standard format. GDPC is written in JAVA and provides (1) data sources available as web services that transfer XML formatted data via the SOAP protocol; (2) a JAVA API for programmatic access to data sources; and (3) a front-end application that allows users to manage data sources, retrieve data based on filters, sort/group data based on property values and save/open the data as XML files. AVAILABILITY: The source code, compiled code, documentation and GDPC Browser are freely available at: www.maizegenetics.net/gdpc/index.html the current release of GDPC is version 1.0, with updated releases planned for the future. Comments are welcome.     

BetaSearch: a new method for querying beta-residue motifs

ABSTRACT: BACKGROUND: Searching for structural motifs across known protein structures can be useful for identifying unrelated proteins with similar function and characterising secondary structures such as beta-sheets. This is infeasible using conventional sequence alignment because linear protein sequences do not contain spatial information. beta-residue motifs are beta-sheet substructures that can be represented as graphs and queried using existing graph indexing methods, however, these approaches are designed for general graphs that do not incorporate the inherent structural constraints of beta-sheets and require computationally-expensive filtering and verification procedures. 3D substructure search methods, on the other hand, allow beta-residue motifs to be queried in a three-dimensional context but at significant computational costs. RESULTS: We developed a new method for querying beta-residue motifs, called BetaSearch, which leverages the natural planar constraints of beta-sheets by indexing them as 2D matrices, thus avoiding much of the computational complexities involved with structural and graph querying. BetaSearch demonstrates faster filtering, verification, and overall query time than existing graph indexing approaches whilst producing comparable index sizes. Compared to 3D substructure search methods, BetaSearch achieves 33 and 240 times speedups over index-based and pairwise alignment-based approaches, respectively. Furthermore, we have presented case-studies to demonstrate its capability of motif matching in sequentially dissimilar proteins and described a method for using BetaSearch to predict beta-strand pairing. CONCLUSIONS: We have demonstrated that BetaSearch is a fast method for querying substructure motifs. The improvements in speed over existing approaches make it useful for efficiently performing high-volume exploratory querying of possible protein substructural motifs or conformations. BetaSearch was used to identify a nearly identical beta-residue motif between an entirely synthetic (Top7) and a naturally-occurring protein (Charcot-Leyden crystal protein), as well as identifying structural similarities between biotin-binding domains of avidin, streptavidin and the lipocalin gamma subunit of human C8. AVAILABILITY: The web-interface, source code, and datasets for BetaSearch can be accessed from http://www.csse.unimelb.edu.au/~hohkhkh1/betasearch.     

Compartmental models with multiple sources of stochastic variability: The one-compartment models with clustering

Previous compartmental models have introduced variability either at the particle or at the replicate level. This paper integrates both types of variability through the concept of clustering. The paper develops two different, general clustered models, each with time-dependent hazard rates for the clusters and for the particles within the clusters, and each with random initial number and sizes of clusters. The coefficient of variation of the total number of particles,CV[X(t)], for either model is shown to be bounded below, under very broad conditions, by the coefficient of variation of the initial number of clusters,CV[c(0)]. This high relative variability of the clustered models makes them potentially very useful in kinetic modeling. In many applications, binding and clustering are common phenomena, and two applications of the models to such phenomena are breifly outlined.     

QPath: a method for querying pathways in a protein-protein interaction network

Background  

Sequence comparison is one of the most prominent tools in biological research, and is instrumental in studying gene function and evolution. The rapid development of high-throughput technologies for measuring protein interactions calls for extending this fundamental operation to the level of pathways in protein networks.     

TAMBIS: transparent access to multiple bioinformatics information sources

SUMMARY: TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) is an application that allows biologists to ask rich and complex questions over a range of bioinformatics resources. It is based on a model of the knowledge of the concepts and their relationships in molecular biology and bioinformatics. AVAILABILITY: TAMBIS is available as an applet from http://img.cs.man.ac.uk/tambis SUPPLEMENTARY: A full manual, tutorial and videos can be found at http://img.cs.man.ac.uk/tambis. CONTACT: tambis@cs.man.ac.uk     

Marine reserve spillover: Modelling from multiple data sources

The functional form of spillover, measured as a gradient of abundance of fish, may provide insight about processes that control the spatial distribution of fish inside and outside the MPA. In this study, we aimed to infer on spillover mechanism of Diplodus spp. (family Sparidae) from a Mediterranean MPA (Carry-le-Rouet, France) from visual censuses and artisanal fisheries data. From the existing literature, three potential functional forms of spillover such as a linear gradient, an exponential gradient and a logistic gradient are defined. Each functional form is included in a spatial generalized linear mixed model allowing accounting for spatial autocorrelation of data. We select between the different forms of gradients by using a Bayesian model selection procedure. In a first step, the functional form of the spillover for visual census and artisanal fishing data is assessed separately. For both sets of data, our model selection favoured the negative exponential model, evidencing a decrease of the spatial abundance of fish vanishing around 1000 m from the MPA border. We combined both datasets in a joint model by including an observability parameter. This parameter captures how the different sources of data quantify the underlying spatial distribution of the harvested species. This enabled us to demonstrate that the different sampling methods do not affect the estimation of the underlying spatial distribution of Diplodus spp. inside and outside the MPA. We show that data from different sources can be pooled through spatial generalized linear mixed model. Our findings allow to better understand the underlying mechanisms that control spillover of fish from MPA.     

Cyclone: java-based querying and computing with Pathway/Genome databases

Cyclone aims at facilitating the use of BioCyc, a collection of Pathway/Genome Databases (PGDBs). Cyclone provides a fully extensible Java Object API to analyze and visualize these data. Cyclone can read and write PGDBs, and can write its own data in the CycloneML format. This format is automatically generated from the BioCyc ontology by Cyclone itself, ensuring continued compatibility. Cyclone objects can also be stored in a relational database CycloneDB. Queries can be written in SQL, and in an intuitive and concise object-oriented query language, Hibernate Query Language (HQL). In addition, Cyclone interfaces easily with Java software including the Eclipse IDE for HQL edition, the Jung API for graph algorithms or Cytoscape for graph visualization. AVAILABILITY: Cyclone is freely available under an open source license at: http://sourceforge.net/projects/nemo-cyclone. SUPPLEMENTARY INFORMATION: For download and installation instructions, tutorials, use cases and examples, see http://nemo-cyclone.sourceforge.net.     

Concordance of species richness patterns among multiple freshwater taxa: a regional perspective

Geographical gradients in species richness and the degree to which different taxa show congruent patterns remain unknown for many taxonomic groups. Here, I examined broad-scale species richness patterns in five groups of freshwater organisms; macrophytes, dragonflies, stoneflies, aquatic beetles and fishes. The analyses were based on provincial distribution records in Denmark, Norway, Sweden and Finland. In general, variation in species richness across provinces was concordant among the groups, but stoneflies showed weaker negative relationships with the other taxonomic groups. Species richness in most groups decreased with increasing latitude and altitude, and a considerable part of the variation was explained by mean July temperature. However, stoneflies showed a reversed pattern, with species richness correlating positively, albeit more weakly, with mean provincial altitude. Nevertheless, combined species richness of all five taxa showed a strong relationship with mean July temperature, accounting for 74% of variation in provincial species richness alone. Such temperature-controlled patterns suggest that regional freshwater biodiversity will strongly respond to climate change, with repercussions for local community organization in freshwater ecosystems in Fennoscandia.     

SPARQLGraph: a web-based platform for graphically querying biological Semantic Web databases

Background

Semantic Web has established itself as a framework for using and sharing data across applications and database boundaries. Here, we present a web-based platform for querying biological Semantic Web databases in a graphical way.

Results

SPARQLGraph offers an intuitive drag & drop query builder, which converts the visual graph into a query and executes it on a public endpoint. The tool integrates several publicly available Semantic Web databases, including the databases of the just recently released EBI RDF platform. Furthermore, it provides several predefined template queries for answering biological questions. Users can easily create and save new query graphs, which can also be shared with other researchers.

Conclusions

This new graphical way of creating queries for biological Semantic Web databases considerably facilitates usability as it removes the requirement of knowing specific query languages and database structures. The system is freely available at http://sparqlgraph.i-med.ac.at.     

GSearcher: agile attribute querying for biological networks

SUMMARY: GSearcher provides a highly interactive user experience in navigating attribute data associated with large and complex biological networks. The user may either perform a quick search using keywords, phrases or regular expressions, or build a complex query with a group of filters for efficient and flexible exploration of large datasets. AVAILABILITY: http://brainarray.mbni.med.umich.edu/gsearcher/.     

Bayesian models for pooling microarray studies with multiple sources of replications

Background  

Biologists often conduct multiple but different cDNA microarray studies that all target the same biological system or pathway. Within each study, replicate slides within repeated identical experiments are often produced. Pooling information across studies can help more accurately identify true target genes. Here, we introduce a method to integrate multiple independent studies efficiently.     

Identification of multiple sources of charge heterogeneity in a recombinant antibody

Seven forms of a therapeutic recombinant antibody that binds to the her2/neu gene product were resolved by cation-exchange chromatography. Structural differences were assigned by peptide mapping and HIC after papain digestion. Deamidation of light chain asparagine 30 to aspartate in one or both light chains is responsible for two acidic forms. A low potency form is due to isomerization of heavy chain aspartate 102; the Asp102 succinimide is also present in a basic peak fraction. Forms with both Asn30 deamidation and Asp102 isomerization modifications were isolated. Deamidation of heavy chain Asn55 to isoaspartate was also detected. Isoelectric focusing in a polyacrylamide gel was used to verify the assignments. All modifications were found in complementarity determining regions.     

Glatiramer acetate treatment of multiple sclerosis: an immunological perspective

Glatiramer acetate (GA) has been used as an immunomodulatory agent for the treatment of relapsing-remitting multiple sclerosis (MS) in the United States since 1996. It is currently one of two first-line agents for use in the treatment of relapsing-remitting MS. GA was the first agent to be used in the treatment of MS that was developed using the animal model of MS called experimental autoimmune encephalomyelitis. In this commentary, we examine the development of GA as a treatment for MS and discuss its mechanism of action as suggested by recent studies using modern immunologic methods.     

JIGSAW: integration of multiple sources of evidence for gene prediction

MOTIVATION: Computational gene finding systems play an important role in finding new human genes, although no systems are yet accurate enough to predict all or even most protein-coding regions perfectly. Ab initio programs can be augmented by evidence such as expression data or protein sequence homology, which improves their performance. The amount of such evidence continues to grow, but computational methods continue to have difficulty predicting genes when the evidence is conflicting or incomplete. Genome annotation pipelines collect a variety of types of evidence about gene structure and synthesize the results, which can then be refined further through manual, expert curation of gene models. RESULTS: JIGSAW is a new gene finding system designed to automate the process of predicting gene structure from multiple sources of evidence, with results that often match the performance of human curators. JIGSAW computes the relative weight of different lines of evidence using statistics generated from a training set, and then combines the evidence using dynamic programming. Our results show that JIGSAW's performance is superior to ab initio gene finding methods and to other pipelines such as Ensembl. Even without evidence from alignment to known genes, JIGSAW can substantially improve gene prediction accuracy as compared with existing methods. AVAILABILITY: JIGSAW is available as an open source software package at http://cbcb.umd.edu/software/jigsaw.     

DiffTool: building,visualizing and querying protein clusters

DiffTool is a resource to build and visualize protein clusters computed from a sequence database. The package provides a clustering tool to construct protein families according to sequence similarities and a web interface to query the corresponding clusters. A subtractive genome analysis tool selects protein families specific for a genome or a group of genomes. For each protein cluster, DiffTool includes access to sequences, coloured multiple alignments and phylogenetic trees. AVAILABILITY: A cluster database built from yeast and complete prokaryotic genomes is queryable at http://bioweb.pasteur.fr/seqanal/difftool. All the Perl sources are freely available to non-profit organizations upon request.