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Vita, R.

Publications and source records attributed to Vita, R..

8 recordsLinked to original sources

Revised Adaptive Immune Receptor Data in the Immune Epitope Database

The Immune Epitope Database (IEDB, iedb.org) is a freely available resource that catalogs experimentally defined immune epitopes and - if available - the immune receptors that recognize them. Currently, the IEDB records [~]185, 000 T cell receptors and [~]5, 000 B cell receptors/antibodies with experimentally verified epitope specificity. Because these receptor data were manually curated from [~]3, 300 references spanning decades, nomenclature inconsistencies present challenges for computational analyses and user queries. To support integrated analysis of the entire dataset, we revised the IEDB receptor data standardization and validation pipeline to flag and correct inaccuracies. Anomalous receptors from over 800 studies were flagged for re-curation. The updated receptor dataset shows greater conformity through consistent gene nomenclature formatting and harmonized CDR sequence delimitation. Taking advantage of the increased receptor data consistency, the IEDB web interface was expanded to include receptor search features directly on the homepage, support V/J gene and species options in the refined receptor search, and allow direct data export in the Adaptive Immune Receptor Repertoire (AIRR) format. We anticipate that the improved receptor data quality will simplify bioinformatics analyses, and facilitate integration of IEDB data into cross-repository data resources, such as the AIRR Knowledge Commons.

bioinformatics↗

Curation at Scale with EPITOME: Extraction Pipeline for Immunological Texts and Open-Source Multimodal Enquiry

The Immune Epitope Database (IEDB, iedb.org) has manually curated epitope data from over 26,000 publications across two decades. With PubMed adding [~]5,000 articles daily, traditional curation methods face scalability challenges. Given the multimodality of data contained in scientific papers, we have sought to build an open-source vision language model (VLM)-based tool that human curators can use to speed up and automate biological data curation. Here we present a multimodal document ingestion and Question-Answering (QnA) pipeline that ties traditional Optical Character Recognition (OCR) and text matching with Vision-Language Model (VLM) capabilities. The system, which we call EPITOME, implements three-stage processing: regex-based epitope and MHC molecule identification, visual element extraction from PDFs, and contextual indexing that links peptide sequences, MHC molecules, and assays to their locations across text, tables, and figures. This indexing is used to supply context for further VLM QnA. Our preliminary results from EPITOME demonstrate promising zero-shot performance of open-source VLMs that suggest promise for accelerating biocuration through a curator-in-the-loop process, with our evaluation identifying strategic points where curator-in-the-loop intervention can enhance overall system accuracy.

bioinformatics↗

VO: The Vaccine Ontology

With the widespread use of vaccines in research and clinical settings, there is an urgent need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO models ontologically vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as RxNorm, CVX, FDA, and USDA. Various VO use cases exist. VO facilitates vaccine standardization in resources such as the VIOLIN vaccine database, ImmPort, and the Vaccine Adjuvant Compendium (VAC). Semantic queries can be made to query VO. VO has been shown to enhance experimental and clinical vaccine data analysis and vaccine literature mining. Overall, VO standardizes vaccine modeling and representation and greatly supports vaccine AI research in the Semantic Web era.

bioinformatics↗

Towards the prediction of non-peptidic epitopes

In-silico methods for the prediction of epitopes can support and improve workflows for vaccine design, antibody production, and disease therapy. So far, the scope of B cell and T cell epitope prediction has been directed exclusively towards peptidic antigens. Nevertheless, various non-peptidic molecular classes can be recognized by immune cells. These compounds have not been systematically studied yet, and prediction approaches are lacking. The ability to predict the epitope activity of non-peptidic compounds could have vast implications; for example, for immunogenic risk assessment of the vast number of drugs and other xenobiotics. Here we present the first general attempt to predict the epitope activity of non-peptidic compounds using the Immune Epitope Database (IEDB) as a source for positive samples. The molecules stored in the Chemical Entities of Biological Interest (ChEBI) database were chosen as background samples. The molecules were clustered into eight homogeneous molecular groups, and classifiers were built for each cluster with the aim of separating the epitopes from the background. Different molecular feature encoding schemes and machine learning models were compared against each other. For those models where a high performance could be achieved based on simple decision rules, the molecular features were then further investigated. Additionally, the findings were used to build a web server that allows for the immunogenic investigation of non-peptidic molecules (http://tools-staging.iedb.org/np_epitope_predictor). The prediction quality was tested with samples from independent evaluation datasets, and the implemented method received noteworthy Receiver Operating Characteristic-Area Under Curve (ROC-AUC) values, ranging from 0.69-0.96 depending on the molecule cluster.

bioinformatics↗

OBO Foundry in 2021: Operationalizing Open Data Principles to Evaluate Ontologies

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies (OBO) Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontologys compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR.

bioinformatics↗

A curated collection of human vaccination response signatures

Recent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications identifying "immune signatures". Unfortunately, these are often described within text, figures, or tables in a format not amenable to computational processing, thus severely hampering our ability to fully exploit this information. Here we present a data model to represent immune signatures, along with the Human Immunology Project Consortium (HIPC) Dashboard (www.hipc-dashboard.org), a web-enabled application to facilitate signature access and querying. The data model captures the biological response components (e.g., genes, proteins, cell types or metabolites) and metadata describing the context under which the signature was identified using standardized terms from established resources (e.g., HGNC, Protein Ontology, Cell Ontology). We have manually curated a collection of >600 immune signatures from >60 published studies profiling human vaccination responses for the current release. The system will aid in building a broader understanding of the human immune response to stimuli by enabling researchers to easily access and interrogate published immune signatures.

bioinformatics↗

TCRMatch: Predicting T-cell receptor specificity based on sequence similarity to previously characterized receptors

The adaptive immune system in vertebrates has evolved to recognize non-self-antigens, such as proteins expressed by infectious agents and mutated cancer cells. T cells play an important role in antigen recognition by expressing a diverse repertoire of antigen-specific receptors, which bind epitopes to mount targeted immune responses. Recent advances in high-throughput sequencing have enabled the routine generation of T-cell receptor (TCR) repertoire data. Identifying the specific epitopes targeted by different TCRs in these data would be valuable. To accomplish that, we took advantage of the ever-increasing number of TCRs with known epitope specificity curated in the Immune Epitope Database (IEDB) since 2004. We compared six metrics of sequence similarity to determine their power to predict if two TCRs have the same epitope specificity. We found that a comprehensive k-mer matching approach produced the best results, which we have implemented into TCRMatch, an openly accessible tool (http://tools.iedb.org/tcrmatch/) that takes TCR {beta}-chain CDR3 sequences as an input, identifies TCRs with a match in the IEDB, and reports the specificity of each match. We anticipate that this tool will provide new insights into T cell responses captured in receptor repertoire and single cell sequencing experiments and will facilitate the development of new strategies for monitoring and treatment of infectious, allergic, and autoimmune diseases, as well as cancer.

immunology↗

NetTCR: sequence-based prediction of TCR binding to peptide-MHC complexes using convolutional neural networks

Predicting epitopes recognized by cytotoxic T cells has been a long standing challenge within the field of immuno- and bioinformatics. While reliable predictions of peptide binding are available for most Major Histocompatibility Complex class I (MHCI) alleles, prediction models of T cell receptor (TCR) interactions with MHC class I-peptide complexes remain poor due to the limited amount of available training data. Recent next generation sequencing projects have however generated a considerable amount of data relating TCR sequences with their cognate HLA-peptide complex target. Here, we utilize such data to train a sequence-based predictor of the interaction between TCRs and peptides presented by the most common human MHCI allele, HLA-A*02:01. Our model is based on convolutional neural networks, which are especially designed to meet the challenges posed by the large length variations of TCRs. We show that such a sequence-based model allows for the identification of TCRs binding a given cognate peptide-MHC target out of a large pool of non-binding TCRs.

bioinformatics↗