Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Engineering Medicine, School of Biological Science and Medical Engineering, Beihang University, No.37 Xueyuan Road, Haidian District, Beijing, 100083, People's Republic of China.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, People's Republic of China.
BMC Bioinformatics. 2021 Jul 23;22(1):382. doi: 10.1186/s12859-021-04301-6.
Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals.
We first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988, p value < 0.0001). Leave one out cross validation (LOOCV) in TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohort from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle.
The model can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy. Furthermore, the prognostic intrinsic features of the neoantigens inferred from this study can be used for identifying neoantigens with high potentials of immunogenicity.
基于新抗原的个性化免疫疗法在黑色素瘤和肺癌中取得了有希望的结果,但很少有基于新抗原的模型在 IDH 野生型 GBM 中表现良好,并且 IDH 野生型 GBM 中,新抗原固有特征与预后之间的关系仍不清楚。我们提出了一种新的基于新抗原内在特征的深度学习模型(neoDL),将 IDH 野生型 GBM 分为具有不同生存时间的亚组。
我们首先为每个与生存相关的新抗原推导内在特征,然后在 TCGA 数据队列中应用 neoDL(AUC = 0.988,p 值 < 0.0001)。TCGA 的留一法交叉验证(LOOCV)表明,neoDL 成功地将 IDH 野生型 GBM 分为不同的预后亚组,这在来自亚洲人群的独立数据队列中得到了进一步验证。通过 neoDL 鉴定的长期生存 IDH 野生型 GBM 被发现具有 12 个保护性新抗原内在特征的特征,并在发育和细胞周期中富集。
该模型可用于治疗性地识别具有良好预后的 IDH 野生型 GBM,这些患者最有可能受益于基于新抗原的个性化免疫治疗。此外,本研究推断的新抗原预后内在特征可用于鉴定具有高免疫原性潜力的新抗原。