Dataset Information

Model selection in the reconstruction of regulatory networks from time-series data.

ABSTRACT:

Background

A widely used approach to reconstruct regulatory networks from time-series data is based on the first-order, linear ordinary differential equations. This approach is justified if it is applied to system relaxations after weak perturbations. However, weak perturbations may not be informative enough to reveal network structures. Other approaches are based on specific models of gene regulation and therefore are of limited applicability.

Findings

We have developed a generalized approach for the reconstruction of regulatory networks from time-series data. This approach uses elements of control theory and the state-space formalism to approximate interactions between two observable nodes (e.g. measured genes). This leads to a reconstruction model formulated in terms of integral equations with flexible kernel functions. We propose a library of kernel functions that can be used for the first insights into network structures.

Conclusion

We have found that the appropriate kernel function significantly increases the accuracy of network reconstruction. The best kernel can be selected using prior information on a few nodes' interactions. We have shown that it may be already possible to select models ensuring reasonable performance even with as small as two known interactions. The developed approaches have been tested with simulated and experimental data.

SUBMITTER: Novikov E

PROVIDER: S-EPMC2688516 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Model selection in the reconstruction of regulatory networks from time-series data.

Novikov Eugene E Barillot Emmanuel E

BMC research notes 20090505

<h4>Background</h4>A widely used approach to reconstruct regulatory networks from time-series data is based on the first-order, linear ordinary differential equations. This approach is justified if it is applied to system relaxations after weak perturbations. However, weak perturbations may not be informative enough to reveal network structures. Other approaches are based on specific models of gene regulation and therefore are of limited applicability.<h4>Findings</h4>We have developed a general ...[more]

PMID: 19416509

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Project description:In this paper, we introduce a novel model selection approach to time series forecasting. For linear stationary processes, such as AR processes, the direction of time is independent of the model parameters. By combining theoretical principles of time-reversibility in time series with conventional modeling approaches such as information criteria, we construct a criterion that employs the backwards prediction (backcast) as a proxy for the forecast. Hereby, we aim to adopt a theoretically grounded, data-driven approach to model selection. The novel criterion is named the backwards validated information criterion (BVIC). The BVIC identifies suitable models by trading off a measure of goodness-of-fit and a models ability to predict backwards. We test the performance of the BVIC by conducting experiments on synthetic and real data. In each experiment, the BVIC is examined in contrast to conventionally employed criteria. Our experimental results suggest that the BVIC has comparable performance as conventional information criteria. Specifically, in most of the experiments performed, we did not find statistically significant differences between the forecast error of the BVIC under certain parameterizations and that of the different information criteria. Nonetheless, it is worth emphasizing that the BVIC guarantees are established by design where the model order penalization term depends on strong mathematical properties of time-reversible time series forecasting properties and a finite data assessment. In particular, the penalization term is replaced by a weighted trade-off between functional dimensions pertaining to forecasting.That said, we observed that the BVIC recovered more accurately the real order of the underlying process than the other criteria, which rely on a static penalization of the model order. Lastly, leveraging the latter property we perform the assessment of the order model (or, memory) of time series pertaining to epileptic seizures recorded using electrocorticographic data. Our results provide converging evidence that the order of the model increases during the epileptic events.

Project description:BackgroundOne of the most challenging tasks in the post-genomic era is to reconstruct the transcriptional regulatory networks. The goal is to reveal, for each gene that responds to a certain biological event, which transcription factors affect its expression, and how a set of transcription factors coordinate to accomplish temporal and spatial specific regulations.ResultsHere we propose a supervised machine learning approach to address these questions. We focus our study on the gene transcriptional regulation of the cell cycle in the budding yeast, thanks to the large amount of data available and relatively well-understood biology, although the main ideas of our method can be applied to other data as well. Our method starts with building an ensemble of decision trees for each microarray data to capture the association between the expression levels of yeast genes and the binding of transcription factors to gene promoter regions, as determined by chromatin immunoprecipitation microarray (ChIP-chip) experiment. Cross-validation experiments show that the method is more accurate and reliable than the naive decision tree algorithm and several other ensemble learning methods. From the decision tree ensembles, we extract logical rules that explain how a set of transcription factors act in concert to regulate the expression of their targets. We further compute a profile for each rule to show its regulation strengths at different time points. We also propose a spline interpolation method to integrate the rule profiles learned from several time series expression data sets that measure the same biological process. We then combine these rule profiles to build a transcriptional regulatory network for the yeast cell cycle. Compared to the results in the literature, our method correctly identifies all major known yeast cell cycle transcription factors, and assigns them into appropriate cell cycle phases. Our method also identifies many interesting synergetic relationships among these transcription factors, most of which are well known, while many of the rest can also be supported by other evidences.ConclusionThe high accuracy of our method indicates that our method is valid and robust. As more gene expression and transcription factor binding data become available, we believe that our method is useful for reconstructing large-scale transcriptional regulatory networks in other species as well.

Dataset Information

Model selection in the reconstruction of regulatory networks from time-series data.

Background

Findings

Conclusion

Publications

Model selection in the reconstruction of regulatory networks from time-series data.

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