Main Strategies for the Identification of Neoantigens.
Main Strategies for the Identification of Neoantigens.
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DOI：
10.3390/cancers12102879
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发表时间：
2020-10-07
期刊：
影响因子：
5.2
通讯作者：
Kosorukov VS
中科院分区：
文献类型：
--
作者：
Gopanenko AV;Kosobokova EN;Kosorukov VS
本文综述了目前用于发现新抗原的方法--肿瘤特异性肽，这些肽是由于突变过程而出现的，并将肿瘤与正常组织区分开来。专注于基于基因组学的方法和计算管道，我们涵盖了从NGS衍生数据开始选择适当候选肽所需的所有步骤。此外，其他方法，如质谱法为基础的和基于结构的方法进行了讨论，突出其优点和缺点。该综述还提供了可用的复杂生物信息学管道的描述，确保自动化数据处理，从而产生新抗原列表。我们提出了可能的理想管道，可以在新抗原识别过程中实施。我们讨论了不同方法产生的结果的整合，以提高新抗原选择的准确性。肿瘤的遗传不稳定性导致许多肿瘤特异性体细胞突变的出现，这些突变可能导致产生由MHC分子呈递在细胞表面上的突变肽。这类肽通常称为新抗原。它们在细胞表面的存在特异性地将肿瘤与健康组织区分开来。这一特征使得新抗原成为免疫治疗的有希望的靶点。高通量基因组学和蛋白质组学的快速发展使得在临床实践中实施这些技术成为可能。特别是，它们为新抗原的研究提供了有用的工具。解决这个问题最有价值的基因组方法是全外显子组测序与RNA-seq相结合。高通量质谱法是直接鉴定MHC结合肽的另一种选择，其能够揭示整个MHC结合肽组。最后，基于结构的预测可以显著提高对影响肽免疫原性的理化和结构特征的理解。结合这些工具的流水线的开发可以提高肽选择过程的准确性并减少所需的时间。在这里，我们提出了一个审查的主要现有的方法来调查新抗原，并建议一个可能的理想管道，考虑到所有的现代趋势的背景下，新抗原的发现。
This review provides an overview of currently available approaches applied for neoantigens discovery—tumor-specific peptides that appeared due to the mutation process and distinguish tumors from normal tissues. Focusing on genomics-based approaches and computational pipelines, we cover all steps required for selecting appropriate candidate peptides starting from NGS-derived data. Moreover, additional approaches such as mass-spectrometry-based and structure-based methods are discussed highlighting their advantages and disadvantages. This review also provides a description of available complex bioinformatics pipelines ensuring automated data processing resulting in a list of neoantigens. We propose the possible ideal pipeline that could be implemented in the neoantigens identification process. We discuss the integration of results generated by different approaches to improve the accuracy of neoantigens selection. Genetic instability of tumors leads to the appearance of numerous tumor-specific somatic mutations that could potentially result in the production of mutated peptides that are presented on the cell surface by the MHC molecules. Peptides of this kind are commonly called neoantigens. Their presence on the cell surface specifically distinguishes tumors from healthy tissues. This feature makes neoantigens a promising target for immunotherapy. The rapid evolution of high-throughput genomics and proteomics makes it possible to implement these techniques in clinical practice. In particular, they provide useful tools for the investigation of neoantigens. The most valuable genomic approach to this problem is whole-exome sequencing coupled with RNA-seq. High-throughput mass-spectrometry is another option for direct identification of MHC-bound peptides, which is capable of revealing the entire MHC-bound peptidome. Finally, structure-based predictions could significantly improve the understanding of physicochemical and structural features that affect the immunogenicity of peptides. The development of pipelines combining such tools could improve the accuracy of the peptide selection process and decrease the required time. Here we present a review of the main existing approaches to investigating the neoantigens and suggest a possible ideal pipeline that takes into account all modern trends in the context of neoantigen discovery.
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影响因子：
7.3
作者：
Bjerregaard AM;Nielsen M;Jurtz V;Barra CM;Hadrup SR;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
MHC I类的性质提出了增强免疫原性的肽。
影响因子：
4.3
作者：
Calis JJ;Maybeno M;Greenbaum JA;Weiskopf D;De Silva AD;Sette A;Keşmir C;Peters B
通讯作者：
Peters B
影响因子：
32.4
作者：
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通讯作者：
Wu CJ
影响因子：
2.9
作者：
Bui, HH;Schiewe, AJ;Haworth, IS
通讯作者：
Haworth, IS
影响因子：
2.4
作者：
Choo SY
通讯作者：
Choo SY