As the amount of biomedical information available in the literature continues to increase, databa... more As the amount of biomedical information available in the literature continues to increase, databases that aggregate this information continue to grow in importance and scope. The population of databases can occur either through fully automated text mining approaches or through manual curation by human subject experts. We here report our experiences in populating the National Institute of Allergy and Infectious Diseases sponsored Immune Epitope Database and Analysis Resource (IEDB, http://iedb.org), which was created in 2003, and as of 2012 captures the epitope information from approximately 99% of all papers published to date that describe immune epitopes (with the exception of cancer and HIV data). This was achieved using a hybrid model based on automated document categorization and extensive human expert involvement. This task required automated scanning of over 22 million PubMed abstracts followed by classification and curation of over 13 000 references, including over 7000 infec...
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute... more 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 d...
The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and a... more The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and analyzing complex immune epitope related data http://www.immuneepitope.org. To identify and extract relevant data from the scientific literature in an efficient and accurate manner, novel processes were developed for manual and semi-automated annotation. Formalized curation strategies enable the processing of a large volume of context-dependent data, which are now available to the scientific community in an accessible and transparent format. The experiences described herein are applicable to other databases housing complex biological data and requiring a high level of curation expertise.
The immune system has evolved to become highly specialized in recognizing and responding to patho... more The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic feature...
Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T ly... more Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T lymphocytes is an essential part of immune surveillance. Each MHC allele has a characteristic peptide binding preference, which can be captured in prediction algorithms, allowing for the rapid scan of entire pathogen proteomes for peptide likely to bind MHC. Here we make public a large set of 48,828 quantitative peptide-binding affinity measurements relating to 48 different mouse, human, macaque, and chimpanzee MHC class I alleles. We use this data to establish a set of benchmark predictions with one neural network method and two matrix-based prediction methods extensively utilized in our groups. In general, the neural network outperforms the matrix-based predictions mainly due to its ability to generalize even on a small amount of data. We also retrieved predictions from tools publicly available on the internet. While differences in the data used to generate these predictions hamper direct comparisons, we do conclude that tools based on combinatorial peptide libraries perform remarkably well. The transparent prediction evaluation on this dataset provides tool developers with a benchmark for comparison of newly developed prediction methods. In addition, to generate and evaluate our own prediction methods, we have established an easily extensible web-based prediction framework that allows automated side-by-side comparisons of prediction methods implemented by experts. This is an advance over the current practice of tool developers having to generate reference predictions themselves, which can lead to underestimating the performance of prediction methods they are not as familiar with as their own. The overall goal of this effort is to provide a transparent prediction evaluation allowing bioinformaticians to identify promising features of prediction methods and providing guidance to immunologists regarding the reliability of prediction tools. Citation: Peters B, Bui HH, Frankild S, Nielsen M, Lundegaard C, et al. (2006) A community resource benchmarking predictions of peptide binding to MHC-I molecules. PLoS Comput Biol 2(6): e65.
The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of information on the 3D st... more The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of information on the 3D structure of biological macromolecules. The PDB's mandate is to disseminate this information in the most usable form and as widely as possible. The current query and distribution system is described and an alpha version of the future re-engineered system introduced.
Epitopes are defined as parts of antigens interacting with receptors of the immune system. Knowle... more 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.
been initiated to support the large-scale identification of immune epitopes derived from NIAID ca... more been initiated to support the large-scale identification of immune epitopes derived from NIAID category A-C pa-La Jolla Institute for Allergy and Immunology 10355 Science Center Drive thogens (Large-Scale Antibody and T cell Epitope Discovery Program). The same programmatic area has San Diego, California 92121 sponsored the creation of a national database, the Immune Epitope Database and Analysis Resource (IEDB), to house existing epitope data as well as data resulting The National Institute of Allergy and Infectious Disfrom these novel discovery efforts. It is anticipated that eases (NIAID), part of the National Institutes of Health these data will be made freely available to the scientific (NIH), recently awarded 14 contracts to fund the community. The IEDB will also house a general analysis Large-Scale Antibody and T Cell Epitope Discovery resource, which will host bioinformatics tools devel-Program. This initiative is designed to identify immune oped to assist in epitope prediction and data analysis, epitopes from selected infectious agents utilizing comand facilitate vaccine development (http://www.niaid. plementary methods for epitope discovery. NIAID will nih.gov/contract/archive/rfp0331.pdf and http://www. make information on each newly identified epitope niaid.nih.gov/contract/archive/RFP0343-0.pdf). A diafreely available to scientists worldwide through the gram illustrating the major components of the IEDB and
Background: Epitopes can be defined as the molecular structures bound by specific receptors, whic... more Background: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens (http://www2.niaid.nih.gov/Biodefense/bandc_priority.htm) and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued.
As the amount of biomedical information available in the literature continues to increase, databa... more As the amount of biomedical information available in the literature continues to increase, databases that aggregate this information continue to grow in importance and scope. The population of databases can occur either through fully automated text mining approaches or through manual curation by human subject experts. We here report our experiences in populating the National Institute of Allergy and Infectious Diseases sponsored Immune Epitope Database and Analysis Resource (IEDB, http://iedb.org), which was created in 2003, and as of 2012 captures the epitope information from approximately 99% of all papers published to date that describe immune epitopes (with the exception of cancer and HIV data). This was achieved using a hybrid model based on automated document categorization and extensive human expert involvement. This task required automated scanning of over 22 million PubMed abstracts followed by classification and curation of over 13 000 references, including over 7000 infec...
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute... more 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 d...
The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and a... more The Immune Epitope Database and Analysis Resource (IEDB) is dedicated to capturing, housing and analyzing complex immune epitope related data http://www.immuneepitope.org. To identify and extract relevant data from the scientific literature in an efficient and accurate manner, novel processes were developed for manual and semi-automated annotation. Formalized curation strategies enable the processing of a large volume of context-dependent data, which are now available to the scientific community in an accessible and transparent format. The experiences described herein are applicable to other databases housing complex biological data and requiring a high level of curation expertise.
The immune system has evolved to become highly specialized in recognizing and responding to patho... more The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic feature...
Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T ly... more Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T lymphocytes is an essential part of immune surveillance. Each MHC allele has a characteristic peptide binding preference, which can be captured in prediction algorithms, allowing for the rapid scan of entire pathogen proteomes for peptide likely to bind MHC. Here we make public a large set of 48,828 quantitative peptide-binding affinity measurements relating to 48 different mouse, human, macaque, and chimpanzee MHC class I alleles. We use this data to establish a set of benchmark predictions with one neural network method and two matrix-based prediction methods extensively utilized in our groups. In general, the neural network outperforms the matrix-based predictions mainly due to its ability to generalize even on a small amount of data. We also retrieved predictions from tools publicly available on the internet. While differences in the data used to generate these predictions hamper direct comparisons, we do conclude that tools based on combinatorial peptide libraries perform remarkably well. The transparent prediction evaluation on this dataset provides tool developers with a benchmark for comparison of newly developed prediction methods. In addition, to generate and evaluate our own prediction methods, we have established an easily extensible web-based prediction framework that allows automated side-by-side comparisons of prediction methods implemented by experts. This is an advance over the current practice of tool developers having to generate reference predictions themselves, which can lead to underestimating the performance of prediction methods they are not as familiar with as their own. The overall goal of this effort is to provide a transparent prediction evaluation allowing bioinformaticians to identify promising features of prediction methods and providing guidance to immunologists regarding the reliability of prediction tools. Citation: Peters B, Bui HH, Frankild S, Nielsen M, Lundegaard C, et al. (2006) A community resource benchmarking predictions of peptide binding to MHC-I molecules. PLoS Comput Biol 2(6): e65.
The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of information on the 3D st... more The Protein Data Bank (PDB; http://www.pdb.org) is the primary source of information on the 3D structure of biological macromolecules. The PDB's mandate is to disseminate this information in the most usable form and as widely as possible. The current query and distribution system is described and an alpha version of the future re-engineered system introduced.
Epitopes are defined as parts of antigens interacting with receptors of the immune system. Knowle... more 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.
been initiated to support the large-scale identification of immune epitopes derived from NIAID ca... more been initiated to support the large-scale identification of immune epitopes derived from NIAID category A-C pa-La Jolla Institute for Allergy and Immunology 10355 Science Center Drive thogens (Large-Scale Antibody and T cell Epitope Discovery Program). The same programmatic area has San Diego, California 92121 sponsored the creation of a national database, the Immune Epitope Database and Analysis Resource (IEDB), to house existing epitope data as well as data resulting The National Institute of Allergy and Infectious Disfrom these novel discovery efforts. It is anticipated that eases (NIAID), part of the National Institutes of Health these data will be made freely available to the scientific (NIH), recently awarded 14 contracts to fund the community. The IEDB will also house a general analysis Large-Scale Antibody and T Cell Epitope Discovery resource, which will host bioinformatics tools devel-Program. This initiative is designed to identify immune oped to assist in epitope prediction and data analysis, epitopes from selected infectious agents utilizing comand facilitate vaccine development (http://www.niaid. plementary methods for epitope discovery. NIAID will nih.gov/contract/archive/rfp0331.pdf and http://www. make information on each newly identified epitope niaid.nih.gov/contract/archive/RFP0343-0.pdf). A diafreely available to scientists worldwide through the gram illustrating the major components of the IEDB and
Background: Epitopes can be defined as the molecular structures bound by specific receptors, whic... more Background: Epitopes can be defined as the molecular structures bound by specific receptors, which are recognized during immune responses. The Immune Epitope Database and Analysis Resource (IEDB) project will catalog and organize information regarding antibody and T cell epitopes from infectious pathogens, experimental antigens and self-antigens, with a priority on NIAID Category A-C pathogens (http://www2.niaid.nih.gov/Biodefense/bandc_priority.htm) and emerging/re-emerging infectious diseases. Both intrinsic structural and phylogenetic features, as well as information relating to the interactions of the epitopes with the host's immune system will be catalogued.
Uploads
Papers by Ward Fleri