Distributed reactive power feedback control for voltage regulation and loss minimization

We consider the problem of exploiting the microgenerators dispersed in the power distribution network in order to provide distributed reactive power compensation for power losses minimization and voltage regulation. In the proposed strategy, microgenerators are smart agents that can measure their phasorial voltage, share these data with the other agents on a cyber layer, and adjust the amount of reactive power injected into the grid, according to a feedback control law that descends from duality-based methods applied to the optimal reactive power flow problem. Convergence to the configuration of minimum losses and feasible voltages is proved analytically for both a synchronous and an asynchronous version of the algorithm, where agents update their state independently one from the other. Simulations are provided in order to illustrate the performance and the robustness of the algorithm, and the innovative feedback nature of such strategy is discussed

Integrated computational extraction of cross-cancer poly-omic signatures

Understanding the interplay between metabolism and genetic regulation is considered key to shed light on the mechanisms underlying cancer onset and progression. In thiswork, we reconstruct a number of tumor-specific genome-scale metabolic models and inspect estimated flux profiles via statistical analysis, characterizing the detailed metabolicresponse associated to altered regulation in various tissues. We thus demonstrate that combining complementary computational techniques it is possible to identify polyomicdifferences and commonalities across cancer types

Clinical stratification improves the diagnostic accuracy of small omics datasets within machine learning and genome-scale metabolic modelling methods

Background: Recently, multi-omic machine learning architectures have been proposed for the early detection of cancer. However, for rare cancers and their associated small datasets, it is still unclear how to use the available multi-omics data to achieve a mechanistic prediction of cancer onset and progression, due to the limited data available. Hepatoblastoma is the most frequent liver cancer in infancy and childhood, and whose incidence has been lately increasing in several developed countries. Even though some studies have been conducted to understand the causes of its onset and discover potential biomarkers, the role of metabolic rewiring has not been investigated in depth so far.Methods: Here, we propose and implement an interpretable multi-omics pipeline that combines mechanis-tic knowledge from genome-scale metabolic models with machine learning algorithms, and we use it to characterise the underlying mechanisms controlling hepatoblastoma.Results and Conclusions: While the obtained machine learning models generally present a high diagnostic classification accuracy, our results show that the type of omics combinations used as input to the machine learning models strongly affects the detection of important genes, reactions and metabolic pathways linked to hepatoblastoma. Our method also suggests that, in the context of computer-aided diagnosis of cancer, optimal diagnostic accuracy can be achieved by adopting a combination of omics that depends on the patient's clinical characteristics

Multi-dimensional experimental and computational exploration of metabolism pinpoints complex probiotic interactions

Multi-strain probiotics are widely regarded as effective products for improving gut microbiota stability and host health, providing advantages over single-strain probiotics. However, in general, it is unclear to what extent different strains would cooperate or compete for resources, and how the establishment of a common biofilm microenvironment could influence their interactions. In this work, we develop an integrative experimental and computational approach to comprehensively assess the metabolic functionality and interactions of probiotics across growth conditions. Our approach combines co-culture assays with genome-scale modelling of metabolism and multivariate data analysis, thus exploiting complementary data- and knowledge-driven systems biology techniques. To show the advantages of the proposed approach, we apply it to the study of the interactions between two widely used probiotic strains of Lactobacillus reuteri and Saccharomyces boulardii, characterising their production potential for compounds that can be beneficial to human health. Our results show that these strains can establish a mixed cooperative-antagonistic interaction best explained by competition for shared resources, with an increased individual exchange but an often decreased net production of amino acids and short-chain fatty acids. Overall, our work provides a strategy that can be used to explore microbial metabolic fingerprints of biotechnological interest, capable of capturing multifaceted equilibria even in simple microbial consortia

Multimodal regularised linear models with flux balance analysis for mechanistic integration of omics data

Motivation: High-throughput biological data, thanks to technological advances, have become cheaper to collect, leading to the availability of vast amounts of omic data of different types. In parallel, the in silico reconstruction and modeling of metabolic systems is now acknowledged as a key tool to complement experimental data on a large scale. The integration of these model- and data-driven information is therefore emerging as a new challenge in systems biology, with no clear guidance on how to better take advantage of the inherent multisource and multiomic nature of these data types while preserving mechanistic interpretation. Results: Here, we investigate different regularization techniques for high-dimensional data derived from the integration of gene expression profiles with metabolic flux data, extracted from strain-specific metabolic models, to improve cellular growth rate predictions. To this end, we propose ad-hoc extensions of previous regularization frameworks including group, view-specific and principal component regularization and experimentally compare them using data from 1143 Saccharomyces cerevisiae strains. We observe a divergence between methods in terms of regression accuracy and integration effectiveness based on the type of regularization employed. In multiomic regression tasks, when learning from experimental and model-generated omic data, our results demonstrate the competitiveness and ease of interpretation of multimodal regularized linear models compared to data-hungry methods based on neural networks. Availability and implementation: All data, models and code produced in this work are available on GitHub at https://github.com/Angione-Lab/HybridGroupIPFLasso_pc2Lasso. Supplementary information: Supplementary data are available at Bioinformatics online

Combining metabolic modelling with machine learning accurately predicts yeast growth rate

New metabolic engineering techniques hold great potential for a range of bio-industrial applications. However, their practical use is hindered by the huge number of possible modifications, especially in eukaryotic organisms. To address this challenge, we present a methodology combining genome-scale metabolic modelling and machine learning to precisely predict cellular phenotypes starting from gene expression readouts. Our methodology enables the identification of candidate genetic manipulations that maximise a desired output--potentially reducing the number of in vitro experiments otherwise required. We apply and validate this methodology to a screen of 1,143 Saccharomyces cerevisiae knockout strains. Within the proposed framework, we compare different combinations of feature selection and supervised machine/deep learning approaches to identify the most effective model

Machine and deep learning meet genome-scale metabolic modeling

Omic data analysis is steadily growing as a driver of basic and applied molecular biology research. Core to the interpretation of complex and heterogeneous biological phenotypes are computational approaches in the fields of statistics and machine learning. In parallel, constraint-based metabolic modeling has established itself as the main tool to investigate large-scale relationships between genotype, phenotype, and environment. The development and application of these methodological frameworks have occurred independently for the most part, whereas the potential of their integration for biological, biomedical, and biotechnological research is less known. Here, we describe how machine learning and constraint-based modeling can be combined, reviewing recent works at the intersection of both domains and discussing the mathematical and practical aspects involved. We overlap systematic classifications from both frameworks, making them accessible to nonexperts. Finally, we delineate potential future scenarios, propose new joint theoretical frameworks, and suggest concrete points of investigation for this joint subfield. A multiview approach merging experimental and knowledge-driven omic data through machine learning methods can incorporate key mechanistic information in an otherwise biologically-agnostic learning process

Metatranscriptomics-guided genome-scale metabolic modeling of microbial communities

Multi-omics data integration via mechanistic models of metabolism is a scalable and flexible framework for exploring biological hypotheses in microbial systems. However, although most microorganisms are uncultur-able, such multi-omics modeling is limited to isolate microbes or simple synthetic communities. Here, we developed an approach for modeling microbial activity and interactions that leverages the reconstruction of metagenome-assembled genomes and associated genome-centric metatranscriptomes. At its core, we designed a method for condition-specific metabolic modeling of microbial communities through the integra-tion of metatranscriptomic data. Using this approach, we explored the behavior of anaerobic digestion con-sortia driven by hydrogen availability and human gut microbiota dysbiosis associated with Crohn's disease, identifying condition-dependent amino acid requirements in archaeal species and a reduced short-chain fatty acid exchange network associated with disease, respectively. Our approach can be applied to complex microbial communities, allowing a mechanistic contextualization of multi-omics data on a metagenome scale

New Interpretation of Galileo\u2019s Arthritis and Blindness

Galileo Galilei (1564-1642) complained of several disorders during his life, the most important of which were chronic arthritic pains and bilateral blindness. These symptoms might result from an immune rheumatic disease, namely reactive arthritis (urethritis, uveitis, arthritis), when Galileo started suffering with an episode of fever in June 1593. Padua University owns the fifth lumbar vertebra of the great scientist and we performed a series of anthropological and radiographic analyses on it. The anthropological measurements showed that the shape of the vertebra was normal as to exclude significant diseases. The study through radiography and Computed Tomography showed only a mild arthrosis documented by small osteophytosis. Eventually the disease evolved into blindness with a pannus restricting the pupils (uveitis). These findings support the occurrence of reactive arthritis. Alternatively to urethral infection, Galileo could have suffered from Chlamydia pneumoniae infection in 1593, which was complicated by reactive arthritis a couple of weeks later. Thereafter he complained several episodes of recurrent arthritis, which eventually culminated into uveitis and bilateral blindness