A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in MATLAB.

EURASIP journal on bioinformatics & systems biology Pub Date : 2016-08-08 eCollection Date: 2016-12-01 DOI:10.1186/s13637-016-0044-y
Shriprakash Sinha
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Abstract

Simulation study in systems biology involving computational experiments dealing with Wnt signaling pathways abound in literature but often lack a pedagogical perspective that might ease the understanding of beginner students and researchers in transition, who intend to work on the modeling of the pathway. This paucity might happen due to restrictive business policies which enforce an unwanted embargo on the sharing of important scientific knowledge. A tutorial introduction to computational modeling of Wnt signaling pathway in a human colorectal cancer dataset using static Bayesian network models is provided. The walkthrough might aid biologists/informaticians in understanding the design of computational experiments that is interleaved with exposition of the Matlab code and causal models from Bayesian network toolbox. The manuscript elucidates the coding contents of the advance article by Sinha (Integr. Biol. 6:1034-1048, 2014) and takes the reader in a step-by-step process of how (a) the collection and the transformation of the available biological information from literature is done, (b) the integration of the heterogeneous data and prior biological knowledge in the network is achieved, (c) the simulation study is designed, (d) the hypothesis regarding a biological phenomena is transformed into computational framework, and (e) results and inferences drawn using d-connectivity/separability are reported. The manuscript finally ends with a programming assignment to help the readers get hands-on experience of a perturbation project. Description of Matlab files is made available under GNU GPL v3 license at the Google code project on https://code.google.com/p/static-bn-for-wnt-signaling-pathway and https: //sites.google.com/site/shriprakashsinha/shriprakashsinha/projects/static-bn-for-wnt-signaling-pathway. Latest updates can be found in the latter website.

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在 MATLAB 中使用静态因果模型对 Wnt 信号通路进行计算建模和模拟的教学演练。
涉及 Wnt 信号通路计算实验的系统生物学模拟研究在文献中比比皆是,但往往缺乏教学视角,这可能会让打算从事通路建模工作的初学者和转型期研究人员更容易理解。这种匮乏可能是由于限制性商业政策造成的,这些政策对重要科学知识的共享实施了不必要的封锁。本文提供了使用静态贝叶斯网络模型对人类结直肠癌数据集中的 Wnt 信号通路进行计算建模的教程介绍。在介绍 Matlab 代码和贝叶斯网络工具箱中的因果模型的同时,还介绍了计算实验的设计。手稿阐明了辛哈(Sinha)预先发表的文章(Integr. Biol.6:1034-1048,2014)的先期文章的编码内容,并带领读者逐步了解如何(a)从文献中收集和转换可用的生物信息,(b)在网络中实现异构数据和先验生物知识的整合,(c)设计模拟研究,(d)将有关生物现象的假设转化为计算框架,以及(e)报告使用 d-connectivity/separability 得出的结果和推论。手稿最后附有编程作业,帮助读者获得扰动项目的实践经验。在 GNU GPL v3 许可下,Matlab 文件的说明可从 https://code.google.com/p/static-bn-for-wnt-signaling-pathway 和 https: //sites.google.com/site/shriprakashsinha/shriprakashsinha/projects/static-bn-for-wnt-signaling-pathway上的谷歌代码项目获取。最新更新可在后一个网站上找到。
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