scholarly journals A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in Matlab

2014 ◽  
Author(s):  
Shriprakash Sinha

AbstractA 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 bio-logists/informaticians in understanding the design of computational experiments that is interleaved with exposition of the Matlab code and causal models from Bayesian Network toolbox. This is done in order to ease the understanding of beginner students and researchers in transition to computational signaling biology, who intend to work in the field of modeling of signaling pathways. The manuscript expounds the computational flow of the contents in advance article1 via code development and takes the reader in a step by step process of how • the collection and the transformation of the available biological information from literature is done, • the integration of the heterogeneous data and prior biological knowledge in the network is achieved, • conditional probability tables for nodes in biologically inspired tables are estimated, • the simulation study is designed, • the hypothesis regarding a biological phenomena is transformed into computational framework, and • 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. Matlab code with dataset is made available under GNU GPL v3 license at google code project on https://code.google.com/p/static-bn-for-wnt-signaling-pathwayInsight, Innovation and IntegrationSimulation study 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 modeling of the pathway. This paucity might happen due to restrictive policies which enforce an unwanted embargo on the sharing of important scientific knowledge. The manuscript elucidates embedding of prior biological knowledge, integration of heterogeneous information, transformation of biological hypothesis into computational framework and design of experiments in a simple manner interleaved with aspects of Bayesian Network toolbox and Matlab code so as to help readers get a feel of a project related to modeling of the pathway.

2015 ◽  
Author(s):  
shriprakash sinha

AbstractEver since the accidental discovery of Wingless [Sharma R.P., Drosophila information service, 1973, 50, p 134], research in the field of Wnt signaling pathway has taken significant strides in wet lab experiments and various cancer clinical trials, augmented by recent developments in advanced computational modeling of the pathway. Information rich gene expression profiles reveal various aspects of the signaling pathway and help in studying different issues simultaneously. Hitherto, not many computational studies exist which incorporate the simultaneous study of these issues. This manuscript • explores the strength of contributing factors in the signaling pathway, • analyzes the existing causal relations among the inter/extracellular factors effecting the pathway based on prior biological knowledge and • investigates the deviations in fold changes in the recently found prevalence of psychophysical laws working in the pathway. To achieve this goal, local and global sensitivity analysis is conducted on the (non)linear responses between the factors obtained from static and time series expression profiles using the density (Hilbert-Schmidt Information Criterion) and variance (Sobol) based sensitivity indices. The results show the advantage of using density based indices over variance based indices mainly due to the former’s employment of distance measures & the kernel trick via Reproducing kernel Hilbert space (RKHS) that capture nonlinear relations among various intra/extracellular factors of the pathway in a higher dimensional space. In time series data, using these indices it is now possible to observe where in time, which factors get influenced & contribute to the pathway, as changes in concentration of the other factors are made. This synergy of prior biological knowledge, sensitivity analysis & representations in higher dimensional spaces can facilitate in time based administration of target therapeutic drugs & reveal hidden biological information within colorectal cancer samples. Code has been made available at Google drive onhttps://drive.google.com/folderview?id=0B7Kkv8wlhPU-Q2NBZGt1ZERrSVE&usp=sharing


2010 ◽  
Vol 34 (8) ◽  
pp. S41-S41
Author(s):  
Yang Bi ◽  
Yun He ◽  
Tingyu Li ◽  
Tao Feng ◽  
Tongchuan He

2006 ◽  
Vol 175 (4S) ◽  
pp. 136-136
Author(s):  
Ralph Buttyan ◽  
Xuezhen Yang ◽  
Min-Wei Chen ◽  
Debra L. Bemis ◽  
Mitchell C. Benson ◽  
...  

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
A Tretyn ◽  
KD Schlüter ◽  
W Janssen ◽  
HA Ghofrani ◽  
F Grimminger ◽  
...  

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