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首页> 外文期刊>BMC Medical Genomics >Directional association test reveals high-quality putative cancer driver biomarkers including noncoding RNAs
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Directional association test reveals high-quality putative cancer driver biomarkers including noncoding RNAs

机译：定向协会测试揭示了高质量推定的癌症驾驶员生物标志物，包括非编码RNA

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Most statistical methods used to identify cancer driver genes are either biased due to choice of assumed parametric models or insensitive to directional relationships important for causal inference. To overcome modeling biases and directional insensitivity, a recent statistical functional chi-squared test (FunChisq) detects directional association via model-free functional dependency. FunChisq examines patterns pointing from independent to dependent variables arising from linear, non-linear, or many-to-one functional relationships. Meanwhile, the Functional Annotation of Mammalian Genome 5 (FANTOM5) project surveyed gene expression at over 200,000 transcription start sites (TSSs) in nearly all human tissue types, primary cell types, and cancer cell lines. The data cover TSSs originated from both coding and noncoding genes. For the vast uncharacterized human TSSs that may exhibit complex patterns in cancer versus normal tissues, the model-free property of FunChisq provides us an unprecedented opportunity to assess the evidence for a gene’s directional effect on human cancer. We first evaluated FunChisq and six other methods using 719 curated cancer genes on the FANTOM5 data. FunChisq performed best in detecting known cancer driver genes from non-cancer genes. We also show the capacity of FunChisq to reveal non-monotonic patterns of functional association, to which typical differential analysis methods such as t-test are insensitive. Further applying FunChisq to screen unannotated TSSs in FANTOM5, we predicted 1108 putative cancer driver noncoding RNAs, stronger than 90% of curated cancer driver genes. Next, we compared leukemia samples against other samples in FANTOM5 and FunChisq predicted 332/79 potential biomarkers for lymphoid/myeloid leukemia, stronger than the TSSs of all 87/100 known driver genes in lymphoid/myeloid leukemia. This study demonstrated the advantage of FunChisq in revealing directional association, especially in detecting non-monotonic patterns. Here, we also provide the most comprehensive catalog of high-quality biomarkers that may play a causative role in human cancers, including putative cancer driver noncoding RNAs and lymphoid/myeloid leukemia specific biomarkers.
机译：用于识别癌症驾驶员基因的大多数统计方法由于选择假定的参数模型或对因因果推断而言重要的定向关系不敏感而偏差。为了克服建模偏差和定向不注心，最近的统计功能Chi平方测试（FunchisQ）通过无模型功能依赖性检测方向关联。 Funchisq检查从独立到从线性，非线性或多对一一函数关系引起的依赖变量指向的模式。同时，在几乎所有人类组织类型，原代细胞类型和癌细胞系中，哺乳动物基因组5（Fantom5）项目的功能注释调查了基因表达在超过20万个转录开始部位（TSSS）。数据覆盖TSS来自编码和非编码基因。对于可能在癌症与正常组织中表现出复杂模式的巨大无特征的人TSS，Funchisq的无模型性质为我们提供了一个前所未有的机会，以评估基因对人类癌症的定向影响的证据。我们首先在Fantom5数据上使用719种疗法癌症基因评估Funchisq和其他六种其他方法。 Funchisq最好在检测来自非癌症基因的已知癌症驾驶员基因。我们还显示了Funchisq的能力，揭示了功能关联的非单调模式，典型的差分分析方法如T检验不敏感。进一步应用Funchisq在Fantom5中筛选Unarnotated TSSS，我们预测1108个推定的癌症驾驶员非编码RNA，强于90％的愈合癌驾驶员基因。接下来，我们将白血病样品与Fantom5和Funchisq预测的332/79潜在的332/79潜在的生物标志物进行了比较了淋巴/髓性白血病的其他样品，比淋巴/髓鞘白血病所有87/100名司机基因的TSSS更强。本研究阐述了Funchisq在揭示方向关联中的优势，尤其在检测非单调模式方面。在这里，我们还提供了最全面的高质量生物标志物目录，可能在人类癌症中发挥致病作用，包括推定的癌症驾驶员不编码的RNA和淋巴/髓性白血病特异性生物标志物。

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