Options
Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstruction
Date Issued
2018-11-01
Date Available
2019-08-26T13:57:22Z
Abstract
Modular Response Analysis (MRA) is a method to reconstruct signalling networks from steady-state perturbation data which has frequently been used in different settings. Since these data are usually noisy due to multi-step measurement procedures and biological variability, it is important to investigate the effect of this noise onto network reconstruction. Here we present a systematic study to investigate propagation of noise from concentration measurements to network structures. Therefore, we design an in silico study of the MAPK and the p53 signalling pathways with realistic noise settings. We make use of statistical concepts and measures to evaluate accuracy and precision of individual inferred interactions and resulting network structures. Our results allow to derive clear recommendations to optimize the performance of MRA based network reconstruction: First, large perturbations are favorable in terms of accuracy even for models with non-linear steady-state response curves. Second, a single control measurement for different perturbation experiments seems to be sufficient for network reconstruction, and third, we recommend to execute the MRA workflow with the mean of different replicates for concentration measurements rather than using computationally more involved regression strategies.
Sponsorship
European Commission Horizon 2020
Other Sponsorship
German Research Foundation via the Cluster of Excellence in Simulation Technology
Type of Material
Journal Article
Publisher
Springer Nature
Journal
Scientific Reports
Volume
8
Issue
Article number 16217
Copyright (Published Version)
2018 The Authors
Language
English
Status of Item
Peer reviewed
ISSN
2045-2322
This item is made available under a Creative Commons License
File(s)
Name
Impact of measurement noise, experimental design, and estimation methods on Modular Response Analysis based network reconstr.pdf
Size
3.61 MB
Format
Owning collection
Scopus© citations
9
Acquisition Date
Apr 18, 2024
Apr 18, 2024
Views
751
Acquisition Date
Apr 18, 2024
Apr 18, 2024
Downloads
392
Last Week
3
3
Last Month
7
7
Acquisition Date
Apr 18, 2024
Apr 18, 2024