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Bjoern Peters

Publications and source records attributed to Bjoern Peters.

27 records · Page 2Linked to original sources

Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method.

BACKGROUND: Many processes in molecular biology involve the recognition of short sequences of nucleic-or amino acids, such as the binding of immunogenic peptides to major histocompatibility complex (MHC) molecules. From experimental data, a model of the sequence specificity of these processes can be constructed, such as a sequence motif, a scoring matrix or an artificial neural network. The purpose of these models is two-fold. First, they can provide a summary of experimental results, allowing for a deeper understanding of the mechanisms involved in sequence recognition. Second, such models can be used to predict the experimental outcome for yet untested sequences. In the past we reported the development of a method to generate such models called the Stabilized Matrix Method (SMM). This method has been successfully applied to predicting peptide binding to MHC molecules, peptide transport by the transporter associated with antigen presentation (TAP) and proteasomal cleavage of protein sequences. RESULTS: Herein we report the implementation of the SMM algorithm as a publicly available software package. Specific features determining the type of problems the method is most appropriate for are discussed. Advantageous features of the package are: (1) the output generated is easy to interpret, (2) input and output are both quantitative, (3) specific computational strategies to handle experimental noise are built in, (4) the algorithm is designed to effectively handle bounded experimental data, (5) experimental data from randomized peptide libraries and conventional peptides can easily be combined, and (6) it is possible to incorporate pair interactions between positions of a sequence. CONCLUSION: Making the SMM method publicly available enables bioinformaticians and experimental biologists to easily access it, to compare its performance to other prediction methods, and to extend it to other applications.

Algorithms↗

The design and implementation of the immune epitope database and analysis resource.

Epitopes are defined as parts of antigens interacting with receptors of the immune system. Knowledge about their intrinsic structure and how they affect the immune response is required to continue development of techniques that detect, monitor, and fight diseases. Their scientific importance is reflected in the vast amount of epitope-related information gathered, ranging from interactions between epitopes and major histocompatibility complex molecules determined by X-ray crystallography to clinical studies analyzing correlates of protection for epitope based vaccines. Our goal is to provide a central resource capable of capturing this information, allowing users to access and connect realms of knowledge that are currently separated and difficult to access. Here, we portray a new initiative, "The Immune Epitope Database and Analysis Resource." We describe how we plan to capture, structure, and store this information, what query interfaces we will make available to the public, and what additional predictive and analytical tools we will provide.

Animals↗

Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications.

Prediction of which peptides can bind major histocompatibility complex (MHC) molecules is commonly used to assist in the identification of T cell epitopes. However, because of the large numbers of different MHC molecules of interest, each associated with different predictive tools, tool generation and evaluation can be a very resource intensive task. A methodology commonly used to predict MHC binding affinity is the matrix or linear coefficients method. Herein, we described Average Relative Binding (ARB) matrix methods that directly predict IC(50) values allowing combination of searches involving different peptide sizes and alleles into a single global prediction. A computer program was developed to automate the generation and evaluation of ARB predictive tools. Using an in-house MHC binding database, we generated a total of 85 and 13 MHC class I and class II matrices, respectively. Results from the automated evaluation of tool efficiency are presented. We anticipate that this automation framework will be generally applicable to the generation and evaluation of large numbers of MHC predictive methods and tools, and will be of value to centralize and rationalize the process of evaluation of MHC predictions. MHC binding predictions based on ARB matrices were made available at http://epitope.liai.org:8080/matrix web server.

Animals↗

Rare case of pulmonary arteriovenous fistula simulating residual defect after transcatheter closure of patent foramen ovale for recurrent paradoxical embolism.

We report on a patient suffering from recurrent cerebrovascular events despite previous transcatheter closure of persistent foramen ovale (PFO) with a Helex occluder. There was evidence of persistent left-to-right atrial shunt shown by transesophageal contrast echocardiography and the patient was admitted to our institution for interventional closure of the supposed residual defect. However, the PFO was completely closed by the device and left pulmonary artery injections showed a pulmonary arteriovenous fistula in the left lower lobe. This rare malformation may well explain the recurrent paradoxical embolism. Transcatheter fistula closure with coils was performed successfully. This case underlines that the existence of an isolated pulmonary arteriovenous fistula as a right-to-left shunt in patients with cryptogenic stroke should not be overlooked, even if a PFO is present and pulmonary arteriovenous fistula is not suggested by the initial physical findings or chest X-ray.

Adult↗

A roadmap for the immunomics of category A-C pathogens.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), recently awarded 14 contracts to fund the Large-Scale Antibody and T Cell Epitope Discovery Program. This initiative is designed to identify immune epitopes from selected infectious agents utilizing complementary methods for epitope discovery. NIAID will make information on each newly identified epitope freely available to scientists worldwide through the Immune Epitope Database and Analysis Resource (IEDB), currently under development. On October 12-14, 2004, representatives of NIAID met in San Diego, California, with a group of investigators from various research institutions to discuss progress and plans for the large-scale epitope discovery projects and for the establishment of the IEDB. It is anticipated that these initiatives will establish detailed maps of immune reactions toward several important complex pathogens, which in turn will foster development of new diagnostic, immune-based therapeutic, and vaccine programs. Herein is an account of the meeting and its results.

Animals↗

Transcatheter therapy of long extreme subatretic aortic coarctations with covered stents.

We report our experience with the transcatheter treatment of long extreme subatretic coarctations in four adult patients by the implantation of covered stents. The minimal narrowing of the stenosis was 0.014'' to 2 mm; the hypoplastic distance measured between 21 and 42 mm. Polytetrafluoroethylene-covered stents 39-50 mm long were implanted and 6 months later redilated. Residual pressure gradients ranged from 0 to 10 mm Hg. One stent fracture required the implantation of a second stent after 6 months. The follow-up period ranges from 18 to 4 months and has been uneventful so far. Covered stents seem to have the potential to extend the limits of interventional therapy to extreme forms of aortic coarctations.

Adolescent↗

Preliminary experience with a new 18 mm Amplatzer PFO occluder for small persistent foramen ovale.

We report our initial experience with a new 18 mm Amplatzer PFO device for the closure of small PFO. Patients were selected by a semiquantitative sizing procedure using the circle of a diagnostic pigtail catheter instead of a sizing balloon. In all eight patients, the device was easy to implant without problems. Due to its size, it has the potential to minimize the risk of inadvertent atrial erosion or perforation after deployment and thus will enhance the safety of interventional PFO closure.

Adult↗

Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools.

A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington, DC to discuss the current state of the B-cell epitope prediction field. Many of the currently available tools were surveyed and a set of recommendations was devised to facilitate improvements in the currently existing tools and to expedite future tool development. An underlying theme of the recommendations put forth by the panel is increased collaboration among research groups. By developing common datasets, standardized data formats, and the means with which to consolidate information, we hope to greatly enhance the development of B-cell epitope prediction tools.

Animals↗