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Biomedical subjects

A Zemla

Publications and source records attributed to A Zemla.

12 recordsLinked to original sources
PubMed2006

MvirDB--a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications.

Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.

Bacterial Proteins↗
PubMed2005

AS2TS system for protein structure modeling and analysis.

We present a set of programs and a website designed to facilitate protein structure comparison and protein structure modeling efforts. Our protein structure analysis and comparison services use the LGA (local-global alignment) program to search for regions of local similarity and to evaluate the level of structural similarity between compared protein structures. To facilitate the homology-based protein structure modeling process, our AL2TS service translates given sequence-structure alignment data into the standard Protein Data Bank (PDB) atom records (coordinates). For a given sequence of amino acids, the AS2TS (amino acid sequence to tertiary structure) system calculates (e.g. using PSI-BLAST PDB analysis) a list of the closest proteins from the PDB, and then a set of draft 3D models is automatically created. Web services are available at http://as2ts.llnl.gov/.

Capsid Proteins↗
PubMed2004

Bovine enterovirus 2: complete genomic sequence and molecular modelling of a reference strain and a wild-type isolate from endemically infected US cattle.

Bovine enteroviruses are members of the family Picornaviridae, genus Enterovirus. Whilst little is known about their pathogenic potential, they are apparently endemic in some cattle and cattle environments. Only one of the two current serotypes has been sequenced completely. In this report, the entire genome sequences of bovine enterovirus 2 (BEV-2) strain PS87 and a recent isolate from an endemically infected herd in Maryland, USA (Wye3A) are presented. The recent isolate clearly segregated phylogenetically with sequences representing the BEV-2 serotype, as did other isolates from the endemic herd. The Wye3A isolate shared 82 % nucleotide sequence identity with the PS87 strain and 68 % identity with a BEV-1 strain (VG5-27). Comparison of BEV-2 and BEV-1 deduced protein sequences revealed 72-73 % identity and showed that most differences were single amino acid changes or single deletions, with the exception of the VP1 protein, where both BEV-2 sequences were 7 aa shorter than that of BEV-1. Homology modelling of the capsid proteins of BEV-2 against protein database entries for picornaviruses indicated six significant differences among bovine enteroviruses and other members of the family Picornaviridae. Five of these were on the 'rim' of the proposed enterovirus receptor-binding site or 'canyon' (VP1) and one was near the base of the canyon (VP3). Two of these regions varied enough to distinguish BEV-2 from BEV-1 strains. This is the first report and analysis of full-length sequences for BEV-2. Continued analysis of these wild-type strains should yield useful information for genotyping enteroviruses and modelling enterovirus capsid structure.

Animals↗
PubMed2001

A study of quality measures for protein threading models.

BACKGROUND: Prediction of protein structures is one of the fundamental challenges in biology today. To fully understand how well different prediction methods perform, it is necessary to use measures that evaluate their performance. Every two years, starting in 1994, the CASP (Critical Assessment of protein Structure Prediction) process has been organized to evaluate the ability of different predictors to blindly predict the structure of proteins. To capture different features of the models, several measures have been developed during the CASP processes. However, these measures have not been examined in detail before. In an attempt to develop fully automatic measures that can be used in CASP, as well as in other type of benchmarking experiments, we have compared twenty-one measures. These measures include the measures used in CASP3 and CASP2 as well as have measures introduced later. We have studied their ability to distinguish between the better and worse models submitted to CASP3 and the correlation between them. RESULTS: Using a small set of 1340 models for 23 different targets we show that most methods correlate with each other. Most pairs of measures show a correlation coefficient of about 0.5. The correlation is slightly higher for measures of similar types. We found that a significant problem when developing automatic measures is how to deal with proteins of different length. Also the comparisons between different measures is complicated as many measures are dependent on the size of the target. We show that the manual assessment can be reproduced to about 70% using automatic measures. Alignment independent measures, detects slightly more of the models with the correct fold, while alignment dependent measures agree better when selecting the best models for each target. Finally we show that using automatic measures would, to a large extent, reproduce the assessors ranking of the predictors at CASP3. CONCLUSIONS: We show that given a sufficient number of targets the manual and automatic measures would have given almost identical results at CASP3. If the intent is to reproduce the type of scoring done by the manual assessor in in CASP3, the best approach might be to use a combination of alignment independent and alignment dependent measures, as used in several recent studies.

Computational Biology↗
PubMed2001

Processing and evaluation of predictions in CASP4.

The Livermore Prediction Center conducted the target collection and prediction submission processes for Critical Assessment of Protein Structure Prediction (CASP4) and Critical Assessment of Fully Automated Structure Prediction Methods (CAFASP2). We have also evaluated all the submitted predictions using criteria and methods developed during the course of three previous CASP experiments and preparation for CASP4. We present an overview of the implemented system. Particular attention is paid to newly developed evaluation techniques and data presentation schemes. With the rapid increase in CASP participation and in the number of submitted predictions, special emphasis is placed on methods allowing reliable pre-classification of submissions and on techniques useful in automated evaluation of predictions. We also present an overview of our website, including target structures, predictions, and their evaluations ( http://predictioncenter.llnl.gov).

Automation↗
PubMed2001

Comparison of performance in successive CASP experiments.

As the number of completed CASP (Critical Assessment of Protein Structure Prediction) experiments grows, so does the need for stable, standard methods for comparing performance in successive experiments. It is critical to develop methods for determining the areas in which there is progress and in which areas are static. We have added an analysis of the CASP4 results to that previously published for CASPs 1, 2, and 3. We again use a unified difficulty scale to permit comparison of performance as a function of target difficulty in the different CASPs. The scale is used to compare performance in aligning target sequences to a structural template. There was a clear improvement in alignment quality between CASP1 (1994) and CASP2 (1996). No change is apparent between CASP2 and CASP3 (1998). There is a small barely detectable improvement between CASP3 and the latest experiment (CASP4, 2000). Alignment remains the major source of error in all models based on less than about 30% sequence identity. Comparison of performance in the new fold modeling regime is complicated by issues in devising an objective target difficulty scale. We have found limited numerical support for significant progress between CASP3 and CASP4 in this area. More subjectively, most observers are convinced that there has been substantial progress. Progress is dominated by a single group.

Models, Molecular↗
PubMed1999

A modified definition of Sov, a segment-based measure for protein secondary structure prediction assessment.

We present a measure for the evaluation of secondary structure prediction methods that is based on secondary structure segments rather than individual residues. The algorithm is an extension of the segment overlap measure Sov, originally defined by Rost et al. (J Mol Biol 1994;235:13-26). The new definition of Sov corrects the normalization procedure and improves Sov's ability to discriminate between similar and dissimilar segment distributions. The method has been comprehensively tested during the second Critical Assessment of Techniques for Protein Structure Prediction (CASP2). Here, we describe the underlying concepts, modifications to the original definition, and their significance.

Algorithms↗
PubMed1999

Processing and analysis of CASP3 protein structure predictions.

Livermore Prediction Center provides basic infrastructure for the CASP (Critical Assessment of Structure Prediction) experiments, including prediction processing and verification servers, a system of prediction evaluation tools, and interactive numerical and graphical displays. Here we outline the essentials of our approach, with discussion of the superposition procedures, definitions of basic measures, and descriptions of new methods developed to analyze predictions. Our primary focus is on the evaluation of three-dimensional models and secondary structure predictions. To put the results of the three prediction experiments held to date on the same footing, the latest CASP3 evaluation criteria were retrospectively applied to both CASP1 and CASP2 predictions. Finally, we give an overview of our website (http:/(/)PredictionCenter.llnl.gov), which makes the target structures, predictions, and the evaluation system accessible to the community.

Amino Acid Sequence↗
PubMed1999

Some measures of comparative performance in the three CASPs.

Performance in the three Critical Assessment of protein Structure Prediction (CASP) experiments has been compared in the areas of alignment accuracy for models based on homology and three-dimensional accuracy for models produced by using ab initio prediction methods. The homologous models span the comparative modeling and fold-recognition regimes. Each CASP target is assigned a relative difficulty based on the extent of sequence identity and the degree of structural overlap with the best available template. There is a clear improvement in alignment accuracy between CASP1 and CASPs 2 and 3 over much of the difficulty scale but no apparent improvement between CASP2 and CASP3. Encouragingly, the best ab initio models of small targets are clearly more accurate in CASP3 than in CASPs 1 and 2.

Algorithms↗
PubMed1997

Numerical criteria for the evaluation of ab initio predictions of protein structure.

As part of the CASP2 protein structure prediction experiment, a set of numerical criteria were defined for the evaluation of "ab initio" predictions. The evaluation package comprises a series of electronic submission formats, a submission validator, evaluation software, and a series of scripts to summarize the results for the CASP2 meeting and for presentation via the World Wide Web (WWW). The evaluation package is accessible for use on new predictions via WWW so that results can be compared to those submitted to CASP2. With further input from the community, the evaluation criteria are expected to evolve into a comprehensive set of measures capturing the overall quality of a prediction as well as critical detail essential for further development of prediction methods. We discuss present measures, limitations of the current criteria, and possible improvements.

Amino Acid Sequence↗
PubMed1997

Criteria for evaluating protein structures derived from comparative modeling.

Following the first experiment for the Critical Assessment of methods for protein Structure Prediction (CASP1), numerical criteria were devised to analyze the performance of prediction methods. We report here the criteria for comparative modeling, and how effective they were in CASP2. These criteria are intended to evolve into a set of numerical measures that provide a comprehensive assessment of the quality of a structure produced by comparative modeling, and provide a means of investigating which modeling methods are most effective, so as to establish where future effort may be most productively applied.

Evaluation Studies as Topic↗