Identification of strategic molecules for future circular supply chains using large reaction networks

Networks of chemical reactions represent relationships between molecules within chemical supply chains and promise to enhance planning of multi-step synthesis routes from bio-renewable feedstocks.</p

Multi-omic network regression: Methodology, tool and case study

The analysis of biological networks is characterized by the definition of precise linear constraints used to cumulatively reduce the solution space of the computed states of a multi-omic (for instance metabolic, transcriptomic and proteomic) model. In this paper, we attempt, for the first time, to combine metabolic modelling and networked Cox regression, using the metabolic model of the bacterium Helicobacter Pylori. This enables a platform both for quantitative analysis of networked regression, but also testing the findings from network regression (a list of significant vectors and their networked relationships) on in vivo transcriptomic data. Data generated from the model, using flux balance analysis to construct a Pareto front, specifically, a trade-off of Oxygen exchange and growth rate and a trade-off of Carbon Dioxide exchange and growth rate, is analysed and then the model is used to quantify the success of the analysis. It was found that using the analysis, reconstruction of the initial data was considerably more successful than a pure noise alternative. Our methodological approach is quite general and it could be of interest for the wider community of complex networks researchers; it is implemented in a software tool, MoNeRe, which is freely available through the Github platform

A Machine Learning Tool for Interpreting Differences in Cognition Using Brain Features

Predicting variability in cognition traits is an attractive and challenging area of research, where different approaches and datasets have been implemented with mixed results. Some powerful Machine Learning algorithms employed before are difficult to interpret, while other algorithms are easy to interpret but might not be as powerful. To improve understanding of individual cognitive differences in humans, we make use of the most recent developments in Machine Learning in which powerful prediction models can be interpreted with confidence. We used neuroimaging data and a variety of behavioural, cognitive, affective and health measures from 905 people obtained from the Human Connectome Project (HCP). As a main contribution of this paper, we show how one could interpret the neuroanatomical basis of cognition, with recent methods which we believe are not yet fully explored in the field. By reducing neuroimages to a well characterised set of features generated from surface-based morphometry and cortical myelin estimates, we make the interpretation of such models easier as each feature is self-explanatory. The code used in this tool is available in a public repository: https://github.com/tjiagoM/interpreting-cognition-paper-2019

Noise and nonlinearities in high-throughput data

High-throughput data analyses are becoming common in biology, communications, economics and sociology. The vast amounts of data are usually represented in the form of matrices and can be considered as knowledge networks. Spectra-based approaches have proved useful in extracting hidden information within such networks and for estimating missing data, but these methods are based essentially on linear assumptions. The physical models of matching, when applicable, often suggest non-linear mechanisms, that may sometimes be identified as noise. The use of non-linear models in data analysis, however, may require the introduction of many parameters, which lowers the statistical weight of the model. According to the quality of data, a simpler linear analysis may be more convenient than more complex approaches. In this paper, we show how a simple non-parametric Bayesian model may be used to explore the role of non-linearities and noise in synthetic and experimental data sets.Comment: 12 pages, 3 figure

Making life difficult for Clostridium difficile: augmenting the pathogen's metabolic model with transcriptomic and codon usage data for better therapeutic target characterization.

BACKGROUND: Clostridium difficile is a bacterium which can infect various animal species, including humans. Infection with this bacterium is a leading healthcare-associated illness. A better understanding of this organism and the relationship between its genotype and phenotype is essential to the search for an effective treatment. Genome-scale metabolic models contain all known biochemical reactions of a microorganism and can be used to investigate this relationship. RESULTS: We present icdf834, an updated metabolic network of C. difficile that builds on iMLTC806cdf and features 1227 reactions, 834 genes, and 807 metabolites. We used this metabolic network to reconstruct the metabolic landscape of this bacterium. The standard metabolic model cannot account for changes in the bacterial metabolism in response to different environmental conditions. To account for this limitation, we also integrated transcriptomic data, which details the gene expression of the bacterium in a wide array of environments. Importantly, to bridge the gap between gene expression levels and protein abundance, we accounted for the synonymous codon usage bias of the bacterium in the model. To our knowledge, this is the first time codon usage has been quantified and integrated into a metabolic model. The metabolic fluxes were defined as a function of protein abundance. To determine potential therapeutic targets using the model, we conducted gene essentiality and metabolic pathway sensitivity analyses and calculated flux control coefficients. We obtained 92.3% accuracy in predicting gene essentiality when compared to experimental data for C. difficile R20291 (ribotype 027) homologs. We validated our context-specific metabolic models using sensitivity and robustness analyses and compared model predictions with literature on C. difficile. The model predicts interesting facets of the bacterium's metabolism, such as changes in the bacterium's growth in response to different environmental conditions. CONCLUSIONS: After an extensive validation process, we used icdf834 to obtain state-of-the-art predictions of therapeutic targets for C. difficile. We show how context-specific metabolic models augmented with codon usage information can be a beneficial resource for better understanding C. difficile and for identifying novel therapeutic targets. We remark that our approach can be applied to investigate and treat against other pathogens.Publication charges for this article have been funded by EpiHealthNet, FP7-PEOPLE-2012-ITN and EU project H2020 FET Open CIRCLE (Coordinating European Research on Molecular Communications) No. 665564

Stochastic analysis of a miRNA-protein toggle switch

none5Within systems biology there is an increasing interest in the stochastic behavior of genetic and biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous time Markov chain (CTMC). In this paper we consider the stochastic properties of a toggle switch, involving a protein compound (E2Fs and Myc) and a miRNA cluster (miR-17-92), known to control the eukaryotic cell cycle and possibly involved in oncogenesis, recently proposed in the literature within a deterministic framework. Due to the inherent stochasticity of biochemical processes and the small number of molecules involved, the stochastic approach should be more correct in describing the real system: we study the agreement between the two approaches by exploring the system parameter space. We address the problem by proposing a simplified version of the model that allows analytical treatment, and by performing numerical simulations for the full model. We observed optimal agreement between the stochastic and the deterministic description of the circuit in a large range of parameters, but some substantial differences arise in at least two cases: (1) when the deterministic system is in the proximity of a transition from a monostable to a bistable configuration, and (2) when bistability (in the deterministic system) is "masked" in the stochastic system by the distribution tails. The approach provides interesting estimates of the optimal number of molecules involved in the toggle switch. Our discussion of the points of strengths, potentiality and weakness of the chemical master equation in systems biology and the differences with respect to deterministic modeling are leveraged in order to provide useful advice for both the bioinformatician and the theoretical scientist.openGiampieri E.; Remondini D.; de Oliveira L.; Castellani G.; Lió P.Giampieri E.; Remondini D.; de Oliveira L.; Castellani G.; Lió P

Multiple verification in computational modeling of bone pathologies

We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the investigation of metabolic syndromes, diabetes and cancer. Our implementation could make use of different logical combinations of these statistical estimators and could incorporate other biomarkers for other systemic co-morbidities (for example diabetes and thalassemia). We are delighted to report that the combination of stochastic modeling with formal methods motivate new diagnostic framework for complex pathologies. In particular our approach takes into consideration important properties of biosystems such as multiscale and self-adaptiveness. The multi-diagnosis could be further expanded, inching towards the complexity of human diseases. Finally, we briefly introduce self-adaptiveness in formal methods which is a key property in the regulative mechanisms of biological systems and well known in other mathematical and engineering areas.Comment: In Proceedings CompMod 2011, arXiv:1109.104

A Novel Methodology for designing Policies in Mobile Crowdsensing Systems

Mobile crowdsensing is a people-centric sensing system based on users' contributions and incentive mechanisms aim at stimulating them. In our work, we have rethought the design of incentive mechanisms through a game-theoretic methodology. Thus, we have introduced a multi-layer social sensing framework, where humans as social sensors interact on multiple social layers and various services. We have proposed to weigh these dynamic interactions by including the concept of homophily and we have modelled the evolutionary dynamics of sensing behaviours by defining a mathematical framework based on multiplex EGT, quantifying the impact of homophily, network heterogeneity and various social dilemmas. We have detected the configurations of social dilemmas and network structures that lead to the emergence and sustainability of human cooperation. Moreover, we have defined and evaluated local and global Nash equilibrium points by including the concepts of homophily and heterogeneity. We have analytically defined and measured novel statistical measures of social honesty, QoI and users' behavioural reputation scores based on the evolutionary dynamics. We have defined the Decision Support System and a novel incentive mechanism by operating on the policies in terms of users' reputation scores, that also incorporate users' behaviours other than quality and quantity of contributions. Experimentally, we have considered the Waze dataset on vehicular traffic monitoring application and derived the disbursement of incentives comparing our method with baselines. Results demonstrate that our methodology, which also includes the local (microscopic) spatio-temporal distribution of behaviours, is able to better discriminate users' behaviours. This multi-scale characterisation of users represents a novel research direction and paves the way for novel policies on mobile crowdsensing systems

Emotion Recognition from EEG Signal Focusing on Deep Learning and Shallow Learning Techniques

Recently, electroencephalogram-based emotion recognition has become crucial in enabling the Human-Computer Interaction (HCI) system to become more intelligent. Due to the outstanding applications of emotion recognition, e.g., person-based decision making, mind-machine interfacing, cognitive interaction, affect detection, feeling detection, etc., emotion recognition has become successful in attracting the recent hype of AI-empowered research. Therefore, numerous studies have been conducted driven by a range of approaches, which demand a systematic review of methodologies used for this task with their feature sets and techniques. It will facilitate the beginners as guidance towards composing an effective emotion recognition system. In this article, we have conducted a rigorous review on the state-of-the-art emotion recognition systems, published in recent literature, and summarized some of the common emotion recognition steps with relevant definitions, theories, and analyses to provide key knowledge to develop a proper framework. Moreover, studies included here were dichotomized based on two categories: i) deep learning-based, and ii) shallow machine learning-based emotion recognition systems. The reviewed systems were compared based on methods, classifier, the number of classified emotions, accuracy, and dataset used. An informative comparison, recent research trends, and some recommendations are also provided for future research directions