Dataset Information

Repairing Boolean logical models from time-series data using Answer Set Programming.

ABSTRACT:

Background

Boolean models of biological signalling-regulatory networks are increasingly used to formally describe and understand complex biological processes. These models may become inconsistent as new data become available and need to be repaired. In the past, the focus has been shed on the inference of (classes of) models given an interaction network and time-series data sets. However, repair of existing models against new data is still in its infancy, where the process is still manually performed and therefore slow and prone to errors.

Results

In this work, we propose a method with an associated tool to suggest repairs over inconsistent Boolean models, based on a set of atomic repair operations. Answer Set Programming is used to encode the minimal repair problem as a combinatorial optimization problem. In particular, given an inconsistent model, the tool provides the minimal repairs that render the model capable of generating dynamics coherent with a (set of) time-series data set(s), considering either a synchronous or an asynchronous updating scheme.

Conclusions

The method was validated using known biological models from different species, as well as synthetic models obtained from randomly generated networks. We discuss the method's limitations regarding each of the updating schemes and the considered minimization algorithm.

SUBMITTER: Lemos A

PROVIDER: S-EPMC6434824 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Repairing Boolean logical models from time-series data using Answer Set Programming.

Lemos Alexandre A Lynce Inês I Monteiro Pedro T PT

Algorithms for molecular biology : AMB 20190325

<h4>Background</h4>Boolean models of biological signalling-regulatory networks are increasingly used to formally describe and understand complex biological processes. These models may become inconsistent as new data become available and need to be repaired. In the past, the focus has been shed on the inference of (classes of) models given an interaction network and time-series data sets. However, repair of existing models against new data is still in its infancy, where the process is still manua ...[more]

PMID: 30962813

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Project description:BackgroundThe impact of a perturbation, over-expression, or repression of a key node on an organism, can be modelled based on a regulatory and/or metabolic network. Integration of these two networks could improve our global understanding of biological mechanisms triggered by a perturbation. This study focuses on improving the modelling of the regulatory network to facilitate a possible integration with the metabolic network. Previously proposed methods that study this problem fail to deal with a real-size regulatory network, computing predictions sensitive to perturbation and quantifying the predicted species behaviour more finely.ResultsTo address previously mentioned limitations, we develop a new method based on Answer Set Programming, MajS. It takes a regulatory network and a discrete partial set of observations as input. MajS tests the consistency between the input data, proposes minimal repairs on the network to establish consistency, and finally computes weighted and signed predictions over the network species. We tested MajS by comparing the HIF-1 signalling pathway with two gene-expression datasets. Our results show that MajS can predict 100% of unobserved species. When comparing MajS with two similar (discrete and quantitative) tools, we observed that compared with the discrete tool, MajS proposes a better coverage of the unobserved species, is more sensitive to system perturbations, and proposes predictions closer to real data. Compared to the quantitative tool, MajS provides more refined discrete predictions that agree with the dynamic proposed by the quantitative tool.ConclusionsMajS is a new method to test the consistency between a regulatory network and a dataset that provides computational predictions on unobserved network species. It provides fine-grained discrete predictions by outputting the weight of the predicted sign as a piece of additional information. MajS' output, thanks to its weight, could easily be integrated with metabolic network modelling.

Dataset Information

Repairing Boolean logical models from time-series data using Answer Set Programming.

Background

Results

Conclusions

Publications

Repairing Boolean logical models from time-series data using Answer Set Programming.

Similar Datasets

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