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Methods Mol Biol ; 1883: 283-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30547405


Inferring gene regulatory networks from expression data is a very challenging problem that has raised the interest of the scientific community. Different algorithms have been proposed to try to solve this issue, but it has been shown that different methods have some particular biases and strengths, and none of them is the best across all types of data and datasets. As a result, the idea of aggregating various network inferences through a consensus mechanism naturally arises. In this chapter, a common framework to standardize already proposed consensus methods is presented, and based on this framework different proposals are introduced and analyzed in two different scenarios: Homogeneous and Heterogeneous. The first scenario reflects situations where the networks to be aggregated are rather similar because they are obtained with inference algorithms working on the same data, whereas the second scenario deals with very diverse networks because various sources of data are used to generate the individual networks. A procedure for combining multiple network inference algorithms is analyzed in a systematic way. The results show that there is a very significant difference between these two scenarios, and that the best way to combine networks in the Heterogeneous scenario is not the most commonly used. We show in particular that aggregation in the Heterogeneous scenario can be very beneficial if the individual networks are combined with our new proposed method ScaleLSum.

Redes Reguladoras de Genes , Modelos Genéticos , Biologia de Sistemas/métodos , Aprendizado de Máquina não Supervisionado , Conjuntos de Dados como Assunto , Biologia de Sistemas/instrumentação
BioData Min ; 10: 15, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28484519


BACKGROUND: Reverse engineering of gene regulatory networks (GRNs) from gene expression data is a classical challenge in systems biology. Thanks to high-throughput technologies, a massive amount of gene-expression data has been accumulated in the public repositories. Modelling GRNs from multiple experiments (also called integrative analysis) has; therefore, naturally become a standard procedure in modern computational biology. Indeed, such analysis is usually more robust than the traditional approaches, which suffer from experimental biases and the low number of samples by analysing individual datasets. To date, there are mainly two strategies for the problem of interest: the first one ("data merging") merges all datasets together and then infers a GRN whereas the other ("networks ensemble") infers GRNs from every dataset separately and then aggregates them using some ensemble rules (such as ranksum or weightsum). Unfortunately, a thorough comparison of these two approaches is lacking. RESULTS: In this work, we are going to present another meta-analysis approach for inferring GRNs from multiple studies. Our proposed meta-analysis approach, adapted to methods based on pairwise measures such as correlation or mutual information, consists of two steps: aggregating matrices of the pairwise measures from every dataset followed by extracting the network from the meta-matrix. Afterwards, we evaluate the performance of the two commonly used approaches mentioned above and our presented approach with a systematic set of experiments based on in silico benchmarks. CONCLUSIONS: We proposed a first systematic evaluation of different strategies for reverse engineering GRNs from multiple datasets. Experiment results strongly suggest that assembling matrices of pairwise dependencies is a better strategy for network inference than the two commonly used ones.