Cancer neoantigen Next-generation sequencing Immune checkpoint blockade Biomarker Immunotherapy
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摘要

Abstract Background Cancer neoantigens are expressed only in cancer cells and presented on the tumor cell surface in complex with major histocompatibility complex (MHC) class I proteins for recognition by cytotoxic T cells. Accurate and rapid identification of neoantigens play a pivotal role in cancer immunotherapy. Although several in silico tools for neoantigen prediction have been presented, limitations of these tools exist. Results We developed pTuneos, a computational pipeline for prioritizing tumor neoantigens from next-generation sequencing data. We tested the performance of pTuneos on the melanoma cancer vaccine cohort data and tumor-infiltrating lymphocyte (TIL)-recognized neopeptide data. pTuneos is able to predict the MHC presentation and T cell recognition ability of the candidate neoantigens, and the actual immunogenicity of single-nucleotide variant (SNV)-based neopeptides considering their natural processing and presentation, surpassing the existing tools with a comprehensive and quantitative benchmark of their neoantigen prioritization performance and running time. pTuneos was further tested on The Cancer Genome Atlas (TCGA) cohort data as well as the melanoma and non-small cell lung cancer (NSCLC) cohort data undergoing checkpoint blockade immunotherapy. The overall neoantigen immunogenicity score proposed by pTuneos is demonstrated to be a powerful and pan-cancer marker for survival prediction compared to traditional well-established biomarkers. Conclusions In summary, pTuneos provides the state-of-the-art one-stop and user-friendly solution for prioritizing SNV-based candidate neoepitopes, which could help to advance research on next-generation cancer immunotherapies and personalized cancer vaccines. pTuneos is available at https://github.com/bm2-lab/pTuneos, with a Docker version for quick deployment at https://cloud.docker.com/u/bm2lab/repository/docker/bm2lab/ptuneos.

译文

背景癌症新抗原仅在癌细胞中表达,并与主要组织相容性复合体 (MHC) I 类蛋白在肿瘤细胞表面呈现,用于细胞毒性 T 细胞的识别。新抗原的准确和快速鉴定在癌症免疫治疗中起着关键作用。尽管已经提出了几种用于新抗原预测的电子工具,但这些工具存在局限性。结果我们开发了 pTuneos,这是一个计算管道,用于从下一代测序数据中优先排列肿瘤新抗原。我们在黑素瘤癌症疫苗队列数据和肿瘤浸润淋巴细胞 (TIL) 识别的新肽数据上测试了 pTuneos 的性能。PTuneos 能够预测候选新抗原的 MHC 呈递和 T 细胞识别能力,以及基于单核苷酸变体 (SNV) 的新肽的实际免疫原性,考虑到它们的自然加工和呈递, 通过全面和定量的新抗原优先化性能和运行时间基准,超越现有工具。PTuneos 在癌症基因组图谱 (TCGA) 队列数据以及接受检查点阻断免疫治疗的黑素瘤和非小细胞肺癌队列数据上进行了进一步测试。与传统的成熟生物标志物相比,pTuneos 提出的总体新抗原免疫原性评分被证明是一种强大的泛癌症标志物,用于生存预测。结论总之,pTuneos 为优先考虑基于 SNV 的候选新表位提供了最先进的一站式和用户友好的解决方案, 这有助于推进下一代癌症免疫疗法和个性化癌症疫苗的研究。PTuneos 可在 https://github.com/bm2-lab/pTuneos ,使用 Docker 版本以便在 https://cloud.docker.com/u/bm2lab/repository/docker/bm2lab/ptuneos 。

Next generation sequencing

肾内泌尿 基础研究 诊断方式
概述  :  

NGS测序技术,是指不基于sanger的高通量DNA测序技术。可以同时对数以百万计或数十亿计的DNA链进行测序,从而大大提高通量。相对于传统的一代测序(sanger测序)来说,二代测序的优点是通量高,缺点是读长短,目前主流的Illumina公司的测序平台常用的读长模式是150PE或者100PE。   原理 二代测序从最开始发展时先后出现了罗氏454平台、Illumina HiSeq系列平台以及ABI公司的Solid平台,

Next   英 /nekst/   美/nɛkst/

释    义   adj. 紧接在后的;贴近的;其次的

               adv. 然后;下次;其次

               n. 下一个人或事件

               prep. 靠近;居于…之后

               det. 下次;紧接在后的;另一个

例    句   What do you think I should do next?  你认为我下一步该怎么办呢?

 

Generation   英 /dʒenə'reɪʃ(ə)n/   美/'dʒɛnə'reʃən/

释    义   n. 一代;产生;一代人;生殖

同根词   generative adj. 生殖的;生产的;有生殖力的;有生产力的

               generational adj. 一代的;生育的

               generator n. 发电机;发生器;生产者

               generate vt. 使形成;发生;生殖

例    句   I weep for our generation!  我为我们这一代哀悼!

 

Sequencing   英 /'siːkwənsɪŋ/   美/'sikwənsɪŋ/

释    义   n. [计] 排序;[计] 定序;排列程序

               v. [计] 定序(sequence的ing形式);使按顺序排列

例    句   In this paper, comparison of the sequencing comparison, hoping to find a suitable algorithm.  本文主要对比各排序进行对比,希望能找出一种合适的算法。

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