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DDGni:使用缺口局部比对从高时间数据推断动态延迟基因网络。

DDGni: dynamic delay gene-network inference from high-temporal data using gapped local alignment.

机构信息

Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, Department of Biology, Hong Kong Baptist University, Kowloon, Department of Computer Science, Faculty of Engineering and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Bioinformatics. 2014 Feb 1;30(3):377-83. doi: 10.1093/bioinformatics/btt692. Epub 2013 Nov 27.

Abstract

MOTIVATION

Inferring gene-regulatory networks is very crucial in decoding various complex mechanisms in biological systems. Synthesis of a fully functional transcriptional factor/protein from DNA involves series of reactions, leading to a delay in gene regulation. The complexity increases with the dynamic delay induced by other small molecules involved in gene regulation, and noisy cellular environment. The dynamic delay in gene regulation is quite evident in high-temporal live cell lineage-imaging data. Although a number of gene-network-inference methods are proposed, most of them ignore the associated dynamic time delay.

RESULTS

Here, we propose DDGni (dynamic delay gene-network inference), a novel gene-network-inference algorithm based on the gapped local alignment of gene-expression profiles. The local alignment can detect short-term gene regulations, that are usually overlooked by traditional correlation and mutual Information based methods. DDGni uses 'gaps' to handle the dynamic delay and non-uniform sampling frequency in high-temporal data, like live cell imaging data. Our algorithm is evaluated on synthetic and yeast cell cycle data, and Caenorhabditis elegans live cell imaging data against other prominent methods. The area under the curve of our method is significantly higher when compared to other methods on all three datasets.

AVAILABILITY

The program, datasets and supplementary files are available at http://www.jjwanglab.org/DDGni/.

摘要

动机

推断基因调控网络对于解码生物系统中的各种复杂机制非常关键。从 DNA 中合成一个完全功能的转录因子/蛋白质涉及一系列反应,导致基因调控的延迟。随着参与基因调控的其他小分子和嘈杂的细胞环境引起的动态延迟的增加,复杂性也会增加。基因调控中的动态延迟在高时间分辨活细胞谱系成像数据中非常明显。尽管已经提出了许多基因网络推断方法,但它们大多数都忽略了相关的动态时间延迟。

结果

在这里,我们提出了 DDGni(动态延迟基因网络推断),这是一种基于基因表达谱的缺口局部比对的新型基因网络推断算法。局部比对可以检测到短期的基因调控,这通常被传统的基于相关性和互信息的方法所忽略。DDGni 使用“缺口”来处理高时间数据(如活细胞成像数据)中的动态延迟和非均匀采样频率。我们的算法在合成数据和酵母细胞周期数据以及秀丽隐杆线虫活细胞成像数据上与其他突出方法进行了评估。与其他方法相比,我们的方法在所有三个数据集上的曲线下面积都显著更高。

可用性

程序、数据集和补充文件可在 http://www.jjwanglab.org/DDGni/ 获得。

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