High-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate the immune response of the T cell. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Based on our previous discoveries, we propose to investigate the distribution of neoantigens with different immunogenicity abilities in 3D genome and propose to adopt this important information into neoantigen prediction. We retrospect the DNA origins of the immuno-positive and immuno-negative neoantigens in the context of 3D genome and discovered that DNA loci of the immuno-positive neoantigens and immuno-negative neoantigens have very different distribution pattern. Specifically, comparing to the background 3D genome, DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We thus used this information into neoantigen prediction and demonstrated the effectiveness of this approach. We believe that the 3D genome information will help to increase the precision of neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

中文翻译：

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一种基于染色质高阶构象的新型新抗原发现方法。

高通量测序技术已经为DNA和RNA带来了可靠且超快速的测序。对于癌症患者的肿瘤细胞，将DNA和RNA测序结果结合在一起，就可以鉴定出刺激T细胞免疫反应的潜在新抗原。但是，当体细胞突变丰富时，根据其激活T细胞免疫反应的能力来有效地对已鉴定的新抗原候选者进行优先排序在计算上存在挑战。已经提出了许多优先化或预测方法来解决这个问题，但是从3D基因组的角度来看，它们都没有考虑新抗原的原始DNA位点。根据我们以前的发现，我们建议研究具有不同免疫原性能力的新抗原在3D基因组中的分布，并建议将此重要信息应用于新抗原预测中。我们回顾了3D基因组中免疫阳性和免疫阴性新抗原的DNA起源，并发现免疫阳性新抗原和免疫阴性新抗原的DNA位点具有非常不同的分布模式。具体而言，与背景3D基因组相比，免疫阳性新抗原的DNA基因座倾向于位于3D基因组中的特定区域。因此，我们将该信息用于新抗原预测，并证明了该方法的有效性。