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一种结合多种方法和数据集用于基因调控网络推断的计算框架。

A computational framework for gene regulatory network inference that combines multiple methods and datasets.

作者信息

Gupta Rita, Stincone Anna, Antczak Philipp, Durant Sarah, Bicknell Roy, Bikfalvi Andreas, Falciani Francesco

机构信息

School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

出版信息

BMC Syst Biol. 2011 Apr 13;5:52. doi: 10.1186/1752-0509-5-52.

Abstract

BACKGROUND

Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective.

RESULTS

This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies.

CONCLUSIONS

The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.

摘要

背景

系统生物学中的逆向工程需要从观测数据推断基因调控网络。这些数据通常包括野生型和突变细胞在给定刺激下的基因表达测量值。研究表明,在网络推断过程中使用多种类型的实验时,准确性更高。因此,开发一种在单一计算框架中嵌入多种信息源的通用且有效的方法是一个有价值的目标。

结果

本文提出了一种新的网络推断方法,该方法使用多目标优化(MOO)来整合多种推断方法和实验。我们通过结合基于常微分方程(ODE)和相关性的网络推断程序以及时间进程和基因失活实验,说明了该方法的潜力。在此我们表明,我们的方法对于广泛的数据集和方法整合策略都是有效的。

结论

我们在本文中提出的方法具有灵活性,可用于受益于在推断过程中整合多种信息源和建模程序的任何场景。此外,将该方法应用于代表细菌和脊椎动物系统的两个案例研究,已显示出在识别重要生物过程的关键调节因子方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c692/3098160/c1dff451a239/1752-0509-5-52-1.jpg

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