PO.BCS01.12 · 生物信息与计算
CEDAR中的癌症表位预测工具与分析流程
Cancer epitope prediction tools & analysis pipelines in CEDAR
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
识别具有免疫原性的癌症表位,包括患者特异性新表位和共有的肿瘤相关抗原(TAA),是开发有效癌症免疫疗法的核心挑战。为加速其发现,癌症表位数据库与分析资源(CEDAR)作为一个面向免疫肿瘤学的综合资源,从文献中整理表位数据并开发定制的计算工具。在此基础上,我们推出了模块化的新一代IEDB工具(NGT)平台(nextgen-tools.iedb.org/),该平台整合了大量以癌症为重点的计算工具。
NGT平台允许用户构建、保存和共享定制化、可重现、端到端的肿瘤抗原发现计算流程。该架构通过应用基于预测和计算得出的相关免疫特征(如抗原表达、抗原呈递、自身相似性和免疫原性)的多重、顺序筛选标准,实现对候选表位的系统性优先排序。
关键工具包括:突变肽生成器(MPG),将基因组变异(如SNV、indel)翻译为候选新表位序列;肽表达注释(PepX),整合来自TCGA和GTEx等资源的公共RNA-Seq数据,以定量肿瘤组织中编码抗原的转录本丰度;患者特异性呈递指标(PHBR),一种评估突变被患者特异性MHC I类等位基因呈递可能性的指标;ICERFIRE(通过肽变异比较,PVC),一种稳健的免疫原性模型,用于预测新表位的T细胞识别潜力;PEPMatch,一种过滤掉与自身肽高度相似的候选新表位的工具,此类相似性可能提示潜在的耐受或自身免疫风险;以及Cluster,将高度相似的肽序列进行分组,以减少冗余并聚焦于最具代表性的候选者以供实验验证。
NGT平台上的CEDAR计算工具及整合的流程架构为癌症免疫学家提供了灵活、易用且先进的资源。这一综合框架加速了将基因组和转录组测序数据转化为临床可操作的候选表位。在此,我们展示了如何将这些整合工具应用于患者层面的分析,实现肿瘤表位的个性化识别与优先排序,以指导癌症疫苗设计和免疫疗法开发。
查看英文原文 English abstract
The identification of immunogenic cancer epitopes, including patient-specific neoepitopes and shared tumor-associated antigens (TAAs), is a central challenge for the development of effective cancer immunotherapies. To accelerate their discovery, the Cancer Epitope Database and Analysis Resource (CEDAR), a comprehensive resource for immuno-oncology, curates epitope data from the literature and develops tailored computational tools. Building on this foundation, we introduce the modular Next-Generation IEDB Tools (NGT) platform (nextgen-tools.iedb.org/) that integrates a wide array of cancer-focused computational tools.
The NGT platform allows users to construct, save, and share customized, reproducible, end-to-end computational pipelines for tumor antigen discovery. This architecture enables systematic prioritization of epitope candidates by applying multiple, sequential filtering criteria based on predicted and calculated relevant immune features, such as antigen expression, antigen presentation, self-similarity, and immunogenicity.
Key tools include the Mutated Peptide Generator (MPG), which translates genomic variants (e.g., SNVs, indels) into candidate neoepitope sequences; Peptide Expression Annotation (PepX), which integrates public RNA-Seq data from resources like TCGA and GTEx to quantify antigen-encoding transcript abundance in tumor tissue; the Patient-Specific Presentation Metric (PHBR), a metric that estimates the likelihood of a mutation being presented by a patient's specific MHC Class I alleles; ICERFIRE (via Peptide Variant Comparison, PVC), a robust immunogenicity model that predicts the T-cell recognition potential of neoepitopes; PEPMatch, a tool to filter out candidate neoepitopes that are highly similar to self-peptides, which can indicate potential tolerance or autoimmunity risks; and Cluster, which groups highly similar peptide sequences to reduce redundancy and focus on the most representative candidates for experimental validation.
The CEDAR computational tools and integrated pipeline architecture on the NGT platform provide cancer immunologists with a flexible, user-friendly, and state-of-the-art resource. This comprehensive framework accelerates the translation of genomic and transcriptomic sequencing data into clinically actionable epitope candidates. Here, we present how these integrated tools can be applied to patient-level analyses, enabling personalized identification and prioritization of tumor epitopes to guide cancer vaccine design and immunotherapy development.
利益披露 Disclosure
I. Carri, None..
J. Greenbaum, None..
Z. Yan, None..
K. Kim, None..
H. Kim, None..
A. L. R. Premlal, None..
D. Marrama, None..
N. Blazeska, None..
M. Nielsen, None..
A. Sette, None.
B. Peters,
Amgen Other, Speaker, consultant.
Sanofi Other, Speaker, consultant.