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首页> 外文会议>IEEE International Conference on Bioinformatics and Biomedicine >A novel scoring estimator to screening for oncogenic chimeric transcripts in cancer transcriptome sequencing
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A novel scoring estimator to screening for oncogenic chimeric transcripts in cancer transcriptome sequencing

机译：一种在癌症转录组测序中筛选致癌嵌合转录本的新型评分估算器

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Based on various genomic information of chimeric transcript, recent studies used machine-learning methods to predict the oncogenic potentials for chimeric transcripts, however these works ignored transcriptional signature of those chimeric transcripts. Based on clonal evolution theory, we hypothesized that a chimeric transcript is more likely to be an oncogenic `driver' mutation, if the neoplastic cells harboring this chimeric mutation has larger clonal size than other neoplastic cells in a particular tumor. Here we proposed a novel method, called iFCR (internal Fusion Clone Ratio), to estimate the ratio of subclone carrying chimeric transcripts to the rest of neoplastic cells in transcriptome sequencing data. To evaluate our hypothesis, we applied iFCR method on two public cancer transcriptome sequencing datasets, one for breast cancer cell line and the other for prostate tumors with adjacent normal tissues. Our results demonstrated that the chimeric transcripts in tumor samples appear to have higher iFCR value than normal tissues, the most frequent prostate cancer fusion mutation, TMPRSS2- ERG, has remarkably higher iFCR value in all three independent patients. Our work providing a novel point of view for screening oncogenesis chimeric transcripts in cancer research.
机译：基于嵌合体转录物的各种基因组信息，最近的研究使用机器学习方法来预测嵌合体转录物的致癌潜力，但是这些工作忽略了那些嵌合体转录物的转录特征。基于克隆进化理论，我们假设，如果一个特定肿瘤中携带这种嵌合突变的肿瘤细胞比其他肿瘤细胞具有更大的克隆大小，那么一个嵌合转录本更可能是致癌的“驱动”突变。在这里，我们提出了一种称为iFCR（内部融合克隆比率）的新方法，用于估计转录组测序数据中携带嵌合转录物的亚克隆与其余赘生性细胞的比率。为了评估我们的假设，我们将iFCR方法应用于两个公共癌症转录组测序数据集，一个用于乳腺癌细胞系，另一个用于与正常组织相邻的前列腺肿瘤。我们的结果表明，肿瘤样品中的嵌合转录物似乎比正常组织具有更高的iFCR值，最常见的前列腺癌融合突变TMPRSS2-ERG在所有三名独立患者中均具有显着更高的iFCR值。我们的工作为筛选癌症研究中的肿瘤发生嵌合转录本提供了一种新颖的观点。

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