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Inference and validation of predictive gene networks from biomedical literature and gene expression data.

ABSTRACT: Although many methods have been developed for inference of biological networks, the validation of the resulting models has largely remained an unsolved problem. Here we present a framework for quantitative assessment of inferred gene interaction networks using knock-down data from cell line experiments. Using this framework we are able to show that network inference based on integration of prior knowledge derived from the biomedical literature with genomic data significantly improves the quality of inferred networks relative to other approaches. Our results also suggest that cell line experiments can be used to quantitatively assess the quality of networks inferred from tumor samples.

SUBMITTER: Olsen C

PROVIDER: S-EPMC4119824 | biostudies-literature | 2014 May-Jun

REPOSITORIES: biostudies-literature

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Inference and validation of predictive gene networks from biomedical literature and gene expression data.

Olsen Catharina C Fleming Kathleen K Prendergast Niall N Rubio Renee R Emmert-Streib Frank F Bontempi Gianluca G Haibe-Kains Benjamin B Quackenbush John J

Genomics 20140329 5-6

Although many methods have been developed for inference of biological networks, the validation of the resulting models has largely remained an unsolved problem. Here we present a framework for quantitative assessment of inferred gene interaction networks using knock-down data from cell line experiments. Using this framework we are able to show that network inference based on integration of prior knowledge derived from the biomedical literature with genomic data significantly improves the quality ...[more]

PMID: 24691108

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Inference and validation of predictive gene networks from biomedical literature and gene expression data

Project description:Although many methods have been developed for inference of biological networks, the validation of the resulting models has largely remained an unsolved problem. Here we present a framework for quantitative assessment of inferred gene interaction networks using knock-down data from cell line experiments. Using this framework we are able to show that network inference based on integration of prior knowledge derived from the biomedical literature with genomic data significantly improves the quality of inferred networks relative to other approaches. Our results also suggest that cell line experiments can be used to quantitatively assess the quality of networks inferred from tumor samples. Knock-down of eight genes were performed on colorectal cancer cell lines to identify the genes whose expression was significantly affected. These genes were subsequently used to validate the quality of our causal gene interaction network.

2013-12-23 | E-GEOD-53091 | biostudies-arrayexpress

Inference and validation of predictive gene networks from biomedical literature and gene expression data

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Integrating literature-constrained and data-driven inference of signalling networks.

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Inference of differential gene regulatory networks based on gene expression and genetic perturbation data.

Project description:MotivationGene regulatory networks (GRNs) of the same organism can be different under different conditions, although the overall network structure may be similar. Understanding the difference in GRNs under different conditions is important to understand condition-specific gene regulation. When gene expression and other relevant data under two different conditions are available, they can be used by an existing network inference algorithm to estimate two GRNs separately, and then to identify the difference between the two GRNs. However, such an approach does not exploit the similarity in two GRNs, and may sacrifice inference accuracy.ResultsIn this paper, we model GRNs with the structural equation model (SEM) that can integrate gene expression and genetic perturbation data, and develop an algorithm named fused sparse SEM (FSSEM), to jointly infer GRNs under two conditions, and then to identify difference of the two GRNs. Computer simulations demonstrate that the FSSEM algorithm outperforms the approaches that estimate two GRNs separately. Analysis of a dataset of lung cancer and another dataset of gastric cancer with FSSEM inferred differential GRNs in cancer versus normal tissues, whose genes with largest network degrees have been reported to be implicated in tumorigenesis. The FSSEM algorithm provides a valuable tool for joint inference of two GRNs and identification of the differential GRN under two conditions.Availability and implementationThe R package fssemR implementing the FSSEM algorithm is available at https://github.com/Ivis4ml/fssemR.git. It is also available on CRAN.Supplementary informationSupplementary data are available at Bioinformatics online.

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dynGENIE3: dynamical GENIE3 for the inference of gene networks from time series expression data.

Project description:The elucidation of gene regulatory networks is one of the major challenges of systems biology. Measurements about genes that are exploited by network inference methods are typically available either in the form of steady-state expression vectors or time series expression data. In our previous work, we proposed the GENIE3 method that exploits variable importance scores derived from Random forests to identify the regulators of each target gene. This method provided state-of-the-art performance on several benchmark datasets, but it could however not specifically be applied to time series expression data. We propose here an adaptation of the GENIE3 method, called dynamical GENIE3 (dynGENIE3), for handling both time series and steady-state expression data. The proposed method is evaluated extensively on the artificial DREAM4 benchmarks and on three real time series expression datasets. Although dynGENIE3 does not systematically yield the best performance on each and every network, it is competitive with diverse methods from the literature, while preserving the main advantages of GENIE3 in terms of scalability.

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| S-EPMC2909222 | biostudies-literature

Integration of steady-state and temporal gene expression data for the inference of gene regulatory networks.

Project description:We develop a new regression algorithm, cMIKANA, for inference of gene regulatory networks from combinations of steady-state and time-series gene expression data. Using simulated gene expression datasets to assess the accuracy of reconstructing gene regulatory networks, we show that steady-state and time-series data sets can successfully be combined to identify gene regulatory interactions using the new algorithm. Inferring gene networks from combined data sets was found to be advantageous when using noisy measurements collected with either lower sampling rates or a limited number of experimental replicates. We illustrate our method by applying it to a microarray gene expression dataset from human umbilical vein endothelial cells (HUVECs) which combines time series data from treatment with growth factor TNF and steady state data from siRNA knockdown treatments. Our results suggest that the combination of steady-state and time-series datasets may provide better prediction of RNA-to-RNA interactions, and may also reveal biological features that cannot be identified from dynamic or steady state information alone. Finally, we consider the experimental design of genomics experiments for gene regulatory network inference and show that network inference can be improved by incorporating steady-state measurements with time-series data.

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