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SILVI,一种用于 T 细胞表位选择的开源管道。

SILVI, an open-source pipeline for T-cell epitope selection.

机构信息

UMR INTERTRYP, IRD, CIRAD, University of Montpellier (I-MUSE), Montpellier, France.

UMR CBGP, INRAE, CIRAD, IRD, Montpellier SupAgro, University of Montpellier (I-MUSE), Montpellier, France.

出版信息

PLoS One. 2022 Sep 7;17(9):e0273494. doi: 10.1371/journal.pone.0273494. eCollection 2022.

Abstract

High-throughput screening of available genomic data and identification of potential antigenic candidates have promoted the development of epitope-based vaccines and therapeutics. Several immunoinformatic tools are available to predict potential epitopes and other immunogenicity-related features, yet it is still challenging and time-consuming to compare and integrate results from different algorithms. We developed the R script SILVI (short for: from in silico to in vivo), to assist in the selection of the potentially most immunogenic T-cell epitopes from Human Leukocyte Antigen (HLA)-binding prediction data. SILVI merges and compares data from available HLA-binding prediction servers, and integrates additional relevant information of predicted epitopes, namely BLASTp alignments with host proteins and physical-chemical properties. The two default criteria applied by SILVI and additional filtering allow the fast selection of the most conserved, promiscuous, strong binding T-cell epitopes. Users may adapt the script at their discretion as it is written in open-source R language. To demonstrate the workflow and present selection options, SILVI was used to integrate HLA-binding prediction results of three example proteins, from viral, bacterial and parasitic microorganisms, containing validated epitopes included in the Immune Epitope Database (IEDB), plus the Human Papillomavirus (HPV) proteome. Applying different filters on predicted IC50, hydrophobicity and mismatches with host proteins allows to significantly reduce the epitope lists with favourable sensitivity and specificity to select immunogenic epitopes. We contemplate SILVI will assist T-cell epitope selections and can be continuously refined in a community-driven manner, helping the improvement and design of peptide-based vaccines or immunotherapies. SILVI development version is available at: github.com/JoanaPissarra/SILVI2020 and https://doi.org/10.5281/zenodo.6865909.

摘要

高通量筛选现有基因组数据和鉴定潜在的抗原候选物促进了基于表位的疫苗和治疗方法的发展。有几种免疫信息学工具可用于预测潜在的表位和其他免疫原性相关特征,但比较和整合来自不同算法的结果仍然具有挑战性和耗时。我们开发了 R 脚本 SILVI(来自 in silico 到 in vivo 的缩写),以帮助从 HLA 结合预测数据中选择潜在最具免疫原性的 T 细胞表位。SILVI 合并和比较了来自现有 HLA 结合预测服务器的数据,并整合了预测表位的其他相关信息,即与宿主蛋白的 BLASTp 比对和理化性质。SILVI 应用的两个默认标准和额外的过滤条件允许快速选择最保守、最混杂、结合最强的 T 细胞表位。用户可以根据自己的判断调整脚本,因为它是用开源 R 语言编写的。为了演示工作流程并展示选择选项,SILVI 用于整合来自病毒、细菌和寄生虫微生物的三个示例蛋白的 HLA 结合预测结果,其中包含包含在免疫表位数据库 (IEDB) 中的验证表位,以及人乳头瘤病毒 (HPV) 蛋白质组。对预测的 IC50、疏水性和与宿主蛋白的错配应用不同的过滤器,可显著减少表位列表,从而提高选择免疫原性表位的敏感性和特异性。我们认为 SILVI 将有助于 T 细胞表位的选择,并可以以社区驱动的方式不断改进,有助于肽基疫苗或免疫疗法的改进和设计。SILVI 开发版本可在以下网址获得:github.com/JoanaPissarra/SILVI2020 和 https://doi.org/10.5281/zenodo.6865909。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe36/9451077/1d32cbdf3f66/pone.0273494.g001.jpg

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