Advances in network-based metabolic pathway analysis and gene expression data integration

Rezola, Alberto; Pey, Jon; Tobalina, Luis; Rubio, Ángel; Beasley, John E.; Planes, Francisco J.

doi:10.1093/bib/bbu009

Cited by 28 publications

(24 citation statements)

References 89 publications

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“…These optimization methods typically enumerate EFMs in an increasing number of reactions and have been proved effective for a number of applications (Rezola et al, 2013(Rezola et al, , 2014. However, they allow us to add only one biological constraint in the search procedure, e.g.…”

Section: Introductionmentioning

confidence: 99%

Direct calculation of elementary flux modes satisfying several biological constraints in genome-scale metabolic networks

Pey

Planes

2014

Bioinformatics

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Motivation: The concept of Elementary Flux Mode (EFM) has been widely used for the past 20 years. However, its application to genomescale metabolic networks (GSMNs) is still under development because of methodological limitations. Therefore, novel approaches are demanded to extend the application of EFMs. A novel family of methods based on optimization is emerging that provides us with a subset of EFMs. Because the calculation of the whole set of EFMs goes beyond our capacity, performing a selective search is a proper strategy. Results: Here, we present a novel mathematical approach calculating EFMs fulfilling additional linear constraints. We validated our approach based on two metabolic networks in which all the EFMs can be obtained. Finally, we analyzed the performance of our methodology in the GSMN of the yeast Saccharomyces cerevisiae by calculating EFMs producing ethanol with a given minimum carbon yield. Overall, this new approach opens new avenues for the calculation of EFMs in GSMNs. Availability and implementation: Matlab code is provided in the supplementary online materials Contact: fplanes@ceit.es.

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Section: Introductionmentioning

confidence: 99%

Direct calculation of elementary flux modes satisfying several biological constraints in genome-scale metabolic networks

Pey

Planes

2014

Bioinformatics

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“…It is particularly interesting the role that they play in particular disease research, where is needed to extract a specific piece of information from the full network. Pathways and Elementary Flux Modes (EFMs) are types of sub-network whose analysis have been remarked by plenty of works [10, 11]. The main drawbacks of using EFMs are the high computational cost to enumerate them and, when obtaining a subset of all the possible EFMs in a GSMN, the uncertainty in having enough biological relevance.…”

Section: Methodsmentioning

confidence: 99%

Improving the EFMs quality by augmenting their representativeness in LP methods

et al. 2018

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BackgroundAlthough cellular metabolism has been widely studied, its fully comprehension is still a challenge. A main tool for this study is the analysis of meaningful pieces of knowledge called modes and, in particular, specially interesting classes of modes such as pathways and Elementary Flux Modes (EFMs). Its study often has to deal with issues such as the appearance of infeasibilities or the difficulty of finding representative enough sets of modes that are free of repetitions. Mode extraction methods usually incorporate strategies devoted to mitigate this phenomena but they still get a high ratio of repetitions in the set of solutions.ResultsThis paper presents a proposal to improve the representativeness of the full set of metabolic reactions in the set of computed modes by penalizing the eventual high frequency of occurrence of some reactions during the extraction. This strategy can be applied to any linear programming based extraction existent method.ConclusionsOur strategy enhances the quality of a set of extracted EFMs favouring the presence of every reaction in it and improving the efficiency by mitigating the occurrence of repeated solutions. The new proposed strategy can complement other EFMs extraction methods based on linear programming. The obtained solutions are more likely to be diverse using less computing effort and improving the efficiency of the extraction.

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“…Obviously the creation and use of these omics-based tools require very specific expertise, one that it is and likely will continue to be out of reach of basic and clinical IBD investigators interested in using omics-derived information for clinical purposes. Fortunately, new generations of mathematically oriented scientists with a focus on human biology have emerged and are quickly expanding their ranks, and they will be ones ‘doing the math' for disease omics goals [22]. Several systems networks already exist that can do so.…”

Section: Omics and The Future Of Ibdmentioning

confidence: 99%

Integrating Omics: The Future of IBD?

Fiocchi¹

2014

Dig Dis

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The complexity of IBD is well recognized as are the putative four major components of its pathogenesis, i.e. environment, genetic makeup, gut microbiota and mucosal immune response. Each of these components is extremely complex on its own, and at present should be more appropriately defined by the terms ‘exposome', ‘genome', ‘microbiome' and ‘immunome', respectively, based on the ‘ome' suffix that refers to a totality of some sort. None of these ‘omes' is apparently capable of causing IBD by itself; it is instead the intricate and reciprocal interaction among them, through the so-called ‘IBD interactome', that results in the emergence of IBD, or more appropriately the ‘IBD integrome'. To deal with and understand such overwhelming biological complexity, new approaches and tools are needed, and these are represented by ‘omics', defined as the study of related sets of biological molecules in a comprehensive fashion, such as genomics, transcriptomics, proteomics, metabolomics, and so on. Numerous bioinformatics-based tools are available to explore and take advantage of the massive amount of information that can be generated by the analysis of the various omes and their interactions, aiming at identifying the molecular interactome underlying any particular status of health and disease. These novel approaches are fully applicable to IBD and allow us to achieve the ultimate goal of developing and applying personalized medicine and far more effective therapies to individual patients with Crohn's disease and ulcerative colitis. For the practicing gastroenterologist, an omics-based delivery of healthcare may be intimidating, but it must be accepted and implemented if he or she is to provide the best possible care to IBD patients.

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Advances in network-based metabolic pathway analysis and gene expression data integration

Cited by 28 publications

References 89 publications

Direct calculation of elementary flux modes satisfying several biological constraints in genome-scale metabolic networks

Direct calculation of elementary flux modes satisfying several biological constraints in genome-scale metabolic networks

Improving the EFMs quality by augmenting their representativeness in LP methods

Integrating Omics: The Future of IBD?

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