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A novel neoantigen discovery approach based on chromatin high order conformation

机译:一种基于染色质高阶确认的新型新稻草发现方法

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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.
机译:高通量测序技术对DNA和RNA产生了可靠和超快速的测序。对于癌症患者的肿瘤细胞,当结合DNA和RNA测序的结果时,可以识别刺激T细胞免疫应答的潜在新抗原。然而,当体细胞突变丰富时,计算挑战,以根据其激活T细胞免疫反应的能力有效地优先考虑所识别的新稻草候选。已经提出了许多优先级或预测方法来解决这个问题,但是它们都不是从3D基因组的角度考虑新稻草原的原​​始DNA基因座。基于我们以前的发现,我们建议探讨新抗原在3D基因组中具有不同免疫原性能力的分布,并提出将这一重要信息采用新洲人预测。我们回顾了在3D基因组的背景下的免疫阳性和免疫阴性新抗原的DNA起源,发现免疫阳性新抗原和免疫阴性Neoantigens的DNA基因座具有非常不同的分布图。具体地,与背景3D基因组相比,免疫阳性新尼久叶茎的DNA基因座倾向于定位在3D基因组中的特定区域。因此,我们将这些信息用作新尼人的预测,并证明了这种方法的有效性。我们认为,3D基因组信息将有助于提高新洲征收优先级和发现的精度,并最终在癌症免疫疗法中受益精密和个性化药物。

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