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Prenet:基于 ATAC-SEQ 数据的预测网络。

Prenet: Predictive network from ATAC-SEQ data.

机构信息

Embryology Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.

School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.

出版信息

J Bioinform Comput Biol. 2020 Feb;18(1):2040003. doi: 10.1142/S021972002040003X.

Abstract

Assays for transposase-accessible chromatin sequencing (ATAC-seq) provides an innovative approach to study chromatin status in multiple cell types. Moreover, it is also possible to efficiently extract differentially accessible chromatin (DACs) regions by using state-of-the-art algorithms (e.g. DESeq2) to predict gene activity in specific samples. Furthermore, it has recently been shown that small dips in sequencing peaks can be attributed to the binding of transcription factors. These dips, also known as footprints, can be used to identify trans-regulating interactions leading to gene expression. Current protocols used to identify footprints (e.g. pyDNAse and HINT-ATAC) have shown limitations resulting in the discovery of many false positive footprints. We generated a novel approach to identify genuine footprints within any given ATAC-seq dataset. Herein, we developed a new pipeline embedding DACs together with footprints resulting in the generation of a dictive gene regulatory work (PreNet) simply from ATAC-seq data. We further demonstrated that PreNet can be used to unveil meaningful molecular regulatory pathways in a given cell type.

摘要

转座酶可及染色质测序(ATAC-seq)分析为研究多种细胞类型中的染色质状态提供了一种创新的方法。此外,通过使用最先进的算法(例如 DESeq2),还可以有效地提取差异可及染色质(DAC)区域,以预测特定样本中的基因活性。此外,最近的研究表明,测序峰的小凹陷可能归因于转录因子的结合。这些凹陷也称为足迹,可以用来识别导致基因表达的转录调控相互作用。目前用于识别足迹的方法(例如 pyDNAse 和 HINT-ATAC)已经显示出局限性,导致发现了许多假阳性足迹。我们提出了一种新的方法来识别给定的 ATAC-seq 数据集中的真实足迹。在这里,我们开发了一种新的管道,将 DACs 与足迹嵌入在一起,从而在没有任何额外实验的情况下,仅从 ATAC-seq 数据生成预测性基因调控工作(PreNet)。我们进一步证明,PreNet 可以用于揭示给定细胞类型中的有意义的分子调控途径。

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