Dataset Information

Immunolyser: A web-based computational pipeline for analysing and mining immunopeptidomic data.

ABSTRACT: Immunopeptidomics has made tremendous contributions to our understanding of antigen processing and presentation, by identifying and quantifying antigenic peptides presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. Large and complex immunopeptidomics datasets can now be routinely generated using Liquid Chromatography-Mass Spectrometry techniques. The analysis of this data - often consisting of multiple replicates/conditions - rarely follows a standard data processing pipeline, hindering the reproducibility and depth of analysis of immunopeptidomic data. Here, we present Immunolyser, an automated pipeline designed to facilitate computational analysis of immunopeptidomic data with a minimal initial setup. Immunolyser brings together routine analyses, including peptide length distribution, peptide motif analysis, sequence clustering, peptide-MHC binding affinity prediction, and source protein analysis. Immunolyser provides a user-friendly and interactive interface via its webserver and is freely available for academic purposes at https://immunolyser.erc.monash.edu/. The open-access source code can be downloaded at our GitHub repository: https://github.com/prmunday/Immunolyser. We anticipate that Immunolyser will serve as a prominent computational pipeline to facilitate effortless and reproducible analysis of immunopeptidomic data.

SUBMITTER: Munday PR

PROVIDER: S-EPMC9988424 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Immunolyser: A web-based computational pipeline for analysing and mining immunopeptidomic data.

Munday Prithvi Raj PR Fehring Joshua J Revote Jerico J Pandey Kirti K Shahbazy Mohammad M Scull Katherine E KE Ramarathinam Sri H SH Faridi Pouya P Croft Nathan P NP Braun Asolina A Li Chen C Purcell Anthony W AW

Computational and structural biotechnology journal 20230218

Immunopeptidomics has made tremendous contributions to our understanding of antigen processing and presentation, by identifying and quantifying antigenic peptides presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. Large and complex immunopeptidomics datasets can now be routinely generated using Liquid Chromatography-Mass Spectrometry techniques. The analysis of this data - often consisting of multiple replicates/conditions - rarely follows a standard data processi ...[more]

PMID: 36890882

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Project description:Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate >8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software. The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. The generated list of candidates (26 in total) was further tested in a functional characterization assay using interferon-γ enzyme-linked immunospot (ELISpot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, nontreated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach.

Project description:BackgroundMedical postgraduates' demand for data capabilities is growing, as biomedical research becomes more data driven, integrative, and computational. In the context of the application of big data in health and medicine, the integration of data mining skills into postgraduate medical education becomes important.ObjectiveThis study aimed to demonstrate the design and implementation of a medical data mining course for medical postgraduates with diverse backgrounds in a medical school.MethodsWe developed a medical data mining course called "Practical Techniques of Medical Data Mining" for postgraduate medical education and taught the course online at Peking Union Medical College (PUMC). To identify the background knowledge, programming skills, and expectations of targeted learners, we conducted a web-based questionnaire survey. After determining the instructional methods to be used in the course, three technical platforms-Rain Classroom, Tencent Meeting, and WeChat-were chosen for online teaching. A medical data mining platform called Medical Data Mining - R Programming Hub (MedHub) was developed for self-learning, which could support the development and comprehensive testing of data mining algorithms. Finally, we carried out a postcourse survey and a case study to demonstrate that our online course could accommodate a diverse group of medical students with a wide range of academic backgrounds and programming experience.ResultsIn total, 200 postgraduates from 30 disciplines participated in the precourse survey. Based on the analysis of students' characteristics and expectations, we designed an optimized course structured into nine logical teaching units (one 4-hour unit per week for 9 weeks). The course covered basic knowledge of R programming, machine learning models, clinical data mining, and omics data mining, among other topics, as well as diversified health care analysis scenarios. Finally, this 9-week course was successfully implemented in an online format from May to July in the spring semester of 2020 at PUMC. A total of 6 faculty members and 317 students participated in the course. Postcourse survey data showed that our course was considered to be very practical (83/83, 100% indicated "very positive" or "positive"), and MedHub received the best feedback, both in function (80/83, 96% chose "satisfied") and teaching effect (80/83, 96% chose "satisfied"). The case study showed that our course was able to fill the gap between student expectations and learning outcomes.ConclusionsWe developed content for a data mining course, with online instructional methods to accommodate the diversified characteristics of students. Our optimized course could improve the data mining skills of medical students with a wide range of academic backgrounds and programming experience.

Dataset Information

Immunolyser: A web-based computational pipeline for analysing and mining immunopeptidomic data.

Publications

Immunolyser: A web-based computational pipeline for analysing and mining immunopeptidomic data.

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