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

Predictive analytics of environmental adaptability in multi-omic network models.

Bacterial phenotypic traits and lifestyles in response to diverse environmental conditions depend on changes in the internal molecular environment. However, predicting bacterial adaptability is still difficult outside of laboratory controlled conditions. Many molecular levels can contribute to the adaptation to a changing environment: pathway structure, codon usage, metabolism. To measure adaptability to changing environmental conditions and over time, we develop a multi-omic model of Escherichia coli that accounts for metabolism, gene expression and codon usage at both transcription and translation levels. After the integration of multiple omics into the model, we propose a multiobjective optimization algorithm to find the allowable and optimal metabolic phenotypes through concurrent maximization or minimization of multiple metabolic markers. In the condition space, we propose Pareto hypervolume and spectral analysis as estimators of short term multi-omic (transcriptomic and metabolic) evolution, thus enabling comparative analysis of metabolic conditions. We therefore compare, evaluate and cluster different experimental conditions, models and bacterial strains according to their metabolic response in a multidimensional objective space, rather than in the original space of microarray data. We finally validate our methods on a phenomics dataset of growth conditions. Our framework, named METRADE, is freely available as a MATLAB toolbox

Poly-omic statistical methods describe cyanobacterial metabolic adaptation to fluctuating environments

In this work, a genome-scale metabolic model of Synechococcus sp. PCC 7002 which utilizes flux balance analysis across multiple layers is analyzed to observe flux response between 23 growth conditions. This is achieved by setting reactions involved in biomass accumulation and energy production as objectives for bi-level linear optimization, thus serving to improve the characterization of mechanisms underlying these processes in photoautotrophic microalgae. Additionally, the incorporation of statistical techniques such as k-means clustering and principal component analysis (PCA) contribute to reducing dimensionality and inferring latent patterns

Mechanistic effects of influenza in bronchial cells through poly-omic genome-scale modelling

In this work we propose regularised bi-level constraint-based modelling to determine the fluxomic profiles for four different influenza viruses, H7N9, H7M7, H3N2 and H5N1. We report here the first step of the analysis of the flux data usingAutoSOME clustering, where we identify novel biomarkers of infection. This is a work in progress that can directly lead to novel therapeutic targets

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