CisPi – a transcriptomic score for disclosing cis-acting disease-associated lincRNAs

Long intergenic noncoding RNAs (lincRNAs) have risen to prominence in cancer biology as new biomarkers of disease.那些转录自活性顺式调控元件(增强子)的LincRNa提供了顺式作用调控的机制性见解;然而,在没有增强剂标志的情况下,computational prediction of cis-acting transcription of lincRNAs remains challenging.在这里,芝加哥大学研究人员介绍了一种新的转录组学方法:顺式调控的lincrna基因关联度量法,称为“cispi”。cispi量化了lincrnas和局部基因表达之间关于它们对干扰反应的相互信息,如疾病风险依赖。To predict risk-dependent lincRNAs in neuroblastoma,an aggressive pediatric cancer,研究人员提出了这个评分方案,通过一个新的并排分析管道来测量lincrnas,它代表RNA序列库中的少数读取。

Altered expression of lincRNAs that stratifies tumor risk is an informative readout of oncogenic enhancer activity.The CisPi metric therefore provides a powerful computational model to identify enhancer-templated RNAs (eRNAs),eRNA-like lincRNAs,或调节局部基因表达的活性增强剂。第一,风险依赖性lincrnas显示活性增强剂,过度表达的神经母细胞瘤易感位点,and uncovered novel clinical biomarkers.Second,优先处理的lincrnas具有显著的预后意义。Third,the predicted target genes further inherited the prognostic significance of these lincRNAs.总而言之,仅RNA序列就足以用我们的方法鉴定疾病相关的lincrna。允许更广泛的应用到增强器标志不可用或显示有限敏感性的环境中。

CisPi metric not only prioritized the phenotype-associated lincRNAs
但预测了lincrnas的靶基因

RNA序列

a1)密度图显示了68个样本中5种lincrna基因对的斯皮尔曼系数。Vertical dashed lines are the significance cutoff at r = 0.6 where signatures dispatch from random controls (dotted lines).Risk-dependent adjacent pairs showing the highest proportion of positive correlation.(a2)Hexbin图显示了已识别的LincRNas(x轴)和基因(y轴)的一致风险依赖性。(c)两类cispi分数的稀疏散点图,one modeling the adjacent targeting (y-axis) and another modeling all potential targets within a TAD (x-axis).橙色对角线表示y=x,标准偏差用两条虚线表示。带注释的lincrna被标记为最近的“目标”基因的名称。水平虚线表示优先顺序的10%截止值(cispi<−10或>40)。(b)人类基因组中34个优先的lincrnas的circos图,观察到14小时上调的基因(红色)和10小时下调的基因(蓝色)毗邻或在TAD。(c) Ingenuity Pathway Analysis (IPA,网址:www.ingenuity.com)在这24个预测的靶基因上(p<0.001),表现出丰富的疾病和功能(图1)以及上游调节分子(图2)。

可利用性– The source code is available on request.The prioritized lincRNAs and their target genes are in theSupplementary Material.

Wang Z,Cunningham JM,Yang XH。(2018) cispi:揭示顺式作用疾病相关基因的转录组学评分. 生物信息学34(17):i664-i670。[ 文章]

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