GroceryDB: Prevalence of Processed Food in Grocery Stores.

The offering of grocery stores is a strong driver of consumer decisions, shaping their diet and long-term health. While highly processed food like packaged products, processed meat, and sweetened soft drinks have been increasingly associated with unhealthy diet, information on the degree of processing characterizing an item in a store is not straightforward to obtain, limiting the ability of individuals to make informed choices. Here we introduce GroceryDB, a database with over 50,000 food items sold by Walmart, Target, and Wholefoods, unveiling how big data can be harnessed to empower consumers and policymakers with systematic access to the degree of processing of the foods they select, and the potential alternatives in the surrounding food environment. The wealth of data collected on ingredient lists and nutrition facts allows a large scale analysis of ingredient patterns and degree of processing stratified by store, food category, and price range. We find that the nutritional choices of the consumers, translated as the degree of food processing, strongly depend on the food categories and grocery stores. Moreover, the data allows us to quantify the individual contribution of over 1,000 ingredients to ultra-processing. GroceryDB and the associated http://TrueFood.Tech/ website make this information accessible, guiding consumers toward less processed food choices while assisting policymakers in reforming the food supply.

An integrative analytical framework to identify healthy, impactful, and equitable foods: a case study on 100% orange juice.

To identify healthy, impactful, and equitable foods, we combined health scores from six diverse nutrient profiling systems (NPS) into a meta-framework (meta-NPS) and paired this with dietary guideline adherence assessment via multilevel regression and poststratification. In a case-study format, a commonly debated beverage formulation - 100% orange juice (OJ) - was chosen to showcase the utility and depth of our framework, systematically scoring high across multiple food systems (i.e. a Meta-Score percentile = 93rd and Stability percentile = 75th) and leading to an expected increase of US dietary fruit guideline adherence by ∼10%. Moreover, the increased adherence varies across the 300 sociodemographic strata, with the benefit patterns being sensitive to absolute or relative quantification of the difference of adherence affected by OJ. In sum, the adaptable, integrative framework we established deepens the science of nutrient profiling and dietary guideline adherence assessment while shedding light on the nuances of defining equitable health effects.

Nutritional redundancy in the human diet and its application in phenotype association studies.

Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as 'nutritional redundancy' and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.

Molecular Interaction Networks and Cardiovascular Disease Risk: The Role of Food Bioactive Small Molecules.

Diet is a well-known modifiable risk factor for cardiovascular diseases, which are the leading cause of death worldwide. However, our current understanding of the human diet is still limited in terms of fully capturing the role of dietary compounds in the intraspecies and interspecies biochemical networks that determine our health. This is due, in part, to a lack of detailed information on the presence of small molecules in food (molecular weight ≤1000 daltons), their amounts, and their interactions with known protein targets. As a result, our ability to develop a mechanistic understanding of how food chemicals impact our health is limited. In recent years, the Foodome project has tackled several aspects of this challenging universe, leveraging the expertise of a diverse group of scientific communities, from computer science to epidemiology. Here, we review the most recent efforts of the Foodome project in mapping the chemical complexity of food and predicting its effect on human health. Leveraging the network medicine framework applied to Amla-a medicinal plant-we offer a rationale for future research on the mechanism of action of food bioactive small molecules, whose designing principles could inspire next-generation drug discovery and combinations.

Improving the generalizability of protein-ligand binding predictions with AI-Bind.

Identifying novel drug-target interactions is a critical and rate-limiting step in drug discovery. While deep learning models have been proposed to accelerate the identification process, here we show that state-of-the-art models fail to generalize to novel (i.e., never-before-seen) structures. We unveil the mechanisms responsible for this shortcoming, demonstrating how models rely on shortcuts that leverage the topology of the protein-ligand bipartite network, rather than learning the node features. Here we introduce AI-Bind, a pipeline that combines network-based sampling strategies with unsupervised pre-training to improve binding predictions for novel proteins and ligands. We validate AI-Bind predictions via docking simulations and comparison with recent experimental evidence, and step up the process of interpreting machine learning prediction of protein-ligand binding by identifying potential active binding sites on the amino acid sequence. AI-Bind is a high-throughput approach to identify drug-target combinations with the potential of becoming a powerful tool in drug discovery.

Machine learning prediction of the degree of food processing.

Despite the accumulating evidence that increased consumption of ultra-processed food has adverse health implications, it remains difficult to decide what constitutes processed food. Indeed, the current processing-based classification of food has limited coverage and does not differentiate between degrees of processing, hindering consumer choices and slowing research on the health implications of processed food. Here we introduce a machine learning algorithm that accurately predicts the degree of processing for any food, indicating that over 73% of the US food supply is ultra-processed. We show that the increased reliance of an individual's diet on ultra-processed food correlates with higher risk of metabolic syndrome, diabetes, angina, elevated blood pressure and biological age, and reduces the bio-availability of vitamins. Finally, we find that replacing foods with less processed alternatives can significantly reduce the health implications of ultra-processed food, suggesting that access to information on the degree of processing, currently unavailable to consumers, could improve population health.

Identification of potent inhibitors of SARS-CoV-2 infection by combined pharmacological evaluation and cellular network prioritization.

Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6,710 clinical and preclinical compounds targeting 2,183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target, and cell interactome produced cellular networks important for infection. This analysis revealed 389 small molecules with micromolar to low nanomolar activities, representing >12 scaffold classes and 813 host targets. Representatives were evaluated for mechanism of action in stable and primary human cell models with SARS-CoV-2 variants and MERS-CoV. One promising candidate, obatoclax, significantly reduced SARS-CoV-2 viral lung load in mice. Ultimately, this work establishes a rigorous approach for future pharmacological and computational identification of host factor dependencies and treatments for viral diseases.

Nutrient concentrations in food display universal behaviour.

Extensive programmes around the world endeavour to measure and catalogue the composition of food. Here we analyse the nutrient content of the full US food supply and show that the concentration of each nutrient follows a universal single-parameter scaling law that accurately captures the eight orders of magnitude in nutrient content variability. We show that the universality is rooted in the biochemical constraints obeyed by the metabolic pathways responsible for nutrient modulation, allowing us to confirm the empirically observed scaling law and to predict its variability in agreement with the data. We propose that the natural nutrient variability in food can be quantitatively formalized. This provides a mathematical rationale for imputing missing values in food composition databases and paves the way towards a quantitative understanding of the impact of food processing on nutrient balance and health effects.

Identification of druggable host targets needed for SARS-CoV-2 infection by combined pharmacological evaluation and cellular network directed prioritization both in vitro and in vivo.

Identification of host factors contributing to replication of viruses and resulting disease progression remains a promising approach for development of new therapeutics. Here, we evaluated 6710 clinical and preclinical compounds targeting 2183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target and cell interactome networking produced cellular networks important for infection. This analysis revealed 389 small molecules, >12 scaffold classes and 813 host targets with micromolar to low nanomolar activities. From these classes, representatives were extensively evaluated for mechanism of action in stable and primary human cell models, and additionally against Beta and Delta SARS-CoV-2 variants and MERS-CoV. One promising candidate, obatoclax, significantly reduced SARS-CoV-2 viral lung load in mice. Ultimately, this work establishes a rigorous approach for future pharmacological and computational identification of novel host factor dependencies and treatments for viral diseases.

Network-based strategies for protein characterization.

Protein structure characterization is fundamental to understand protein properties, such as folding process and protein resistance to thermal stress, up to unveiling organism pathologies (e.g., prion disease). In this chapter, we provide an overview on how the spectral properties of the networks reconstructed from the Protein Contact Map (PCM) can be used to generate informative observables. As a specific case study, we apply two different network approaches to an example protein dataset, for the aim of discriminating protein folding state, and for the reconstruction of protein 3D structure.

Node Centrality Measures Identify Relevant Structural MRI Features of Subjects with Autism.

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social interaction and communication and restricted patterns of behavior, interests, and activities. Although the etiopathogenesis of idiopathic ASD has not been fully elucidated, compelling evidence suggests an interaction between genetic liability and environmental factors in producing early alterations of structural and functional brain development that are detectable by magnetic resonance imaging (MRI) at the group level. This work shows the results of a network-based approach to characterize not only variations in the values of the extracted features but also in their mutual relationships that might reflect underlying brain structural differences between autistic subjects and healthy controls. We applied a network-based analysis on sMRI data from the Autism Brain Imaging Data Exchange I (ABIDE-I) database, containing 419 features extracted with FreeSurfer software. Two networks were generated: one from subjects with autistic disorder (AUT) (DSM-IV-TR), and one from typically developing controls (TD), adopting a subsampling strategy to overcome class imbalance (235 AUT, 418 TD). We compared the distribution of several node centrality measures and observed significant inter-class differences in averaged centralities. Moreover, a single-node analysis allowed us to identify the most relevant features that distinguished the groups.

A systematic comprehensive longitudinal evaluation of dietary factors associated with acute myocardial infarction and fatal coronary heart disease.

Environmental factors, and in particular diet, are known to play a key role in the development of Coronary Heart Disease. Many of these factors were unveiled by detailed nutritional epidemiology studies, focusing on the role of a single nutrient or food at a time. Here, we apply an Environment-Wide Association Study approach to Nurses' Health Study data to explore comprehensively and agnostically the association of 257 nutrients and 117 foods with coronary heart disease risk (acute myocardial infarction and fatal coronary heart disease). After accounting for multiple testing, we identify 16 food items and 37 nutrients that show statistically significant association - while adjusting for potential confounding and control variables such as physical activity, smoking, calorie intake, and medication use - among which 38 associations were validated in Nurses' Health Study II. Our implementation of Environment-Wide Association Study successfully reproduces prior knowledge of diet-coronary heart disease associations in the epidemiological literature, and helps us detect new associations that were only marginally studied, opening potential avenues for further extensive experimental validation. We also show that Environment-Wide Association Study allows us to identify a bipartite food-nutrient network, highlighting which foods drive the associations of specific nutrients with coronary heart disease risk.

Exploring food contents in scientific literature with FoodMine.

Thanks to the many chemical and nutritional components it carries, diet critically affects human health. However, the currently available comprehensive databases on food composition cover only a tiny fraction of the total number of chemicals present in our food, focusing on the nutritional components essential for our health. Indeed, thousands of other molecules, many of which have well documented health implications, remain untracked. To explore the body of knowledge available on food composition, we built FoodMine, an algorithm that uses natural language processing to identify papers from PubMed that potentially report on the chemical composition of garlic and cocoa. After extracting from each paper information on the reported quantities of chemicals, we find that the scientific literature carries extensive information on the detailed chemical components of food that is currently not integrated in databases. Finally, we use unsupervised machine learning to create chemical embeddings, finding that the chemicals identified by FoodMine tend to have direct health relevance, reflecting the scientific community's focus on health-related chemicals in our food.

Network integration of multi-tumour omics data suggests novel targeting strategies.

We characterize different tumour types in search for multi-tumour drug targets, in particular aiming for drug repurposing and novel drug combinations. Starting from 11 tumour types from The Cancer Genome Atlas, we obtain three clusters based on transcriptomic correlation profiles. A network-based analysis, integrating gene expression profiles and protein interactions of cancer-related genes, allows us to define three cluster-specific signatures, with genes belonging to NF-κB signaling, chromosomal instability, ubiquitin-proteasome system, DNA metabolism, and apoptosis biological processes. These signatures have been characterized by different approaches based on mutational, pharmacological and clinical evidences, demonstrating the validity of our selection. Moreover, we define new pharmacological strategies validated by in vitro experiments that show inhibition of cell growth in two tumour cell lines, with significant synergistic effect. Our study thus provides a list of genes and pathways that could possibly be used, singularly or in combination, for the design of novel treatment strategies.

Entropy-Based Network Representation of the Individual Metabolic Phenotype.

We approach here the problem of defining and estimating the nature of the metabolite-metabolite association network underlying the human individual metabolic phenotype in healthy subjects. We retrieved significant associations using an entropy-based approach and a multiplex network formalism. We defined a significantly over-represented network formed by biologically interpretable metabolite modules. The entropy of the individual metabolic phenotype is also introduced and discussed.

Network measures for protein folding state discrimination.

Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there is not a first-principle model to explain this different behavior. We exploit the network properties of protein structures by introducing novel observables to address the problem of classifying the different types of folding kinetics. These observables display a plain physical meaning, in terms of vibrational modes, possible configurations compatible with the native protein structure, and folding cooperativity. The relevance of these observables is supported by a classification performance up to 90%, even with simple classifiers such as discriminant analysis.

Control of Multilayer Networks.

The controllability of a network is a theoretical problem of relevance in a variety of contexts ranging from financial markets to the brain. Until now, network controllability has been characterized only on isolated networks, while the vast majority of complex systems are formed by multilayer networks. Here we build a theoretical framework for the linear controllability of multilayer networks by mapping the problem into a combinatorial matching problem. We found that correlating the external signals in the different layers can significantly reduce the multiplex network robustness to node removal, as it can be seen in conjunction with a hybrid phase transition occurring in interacting Poisson networks. Moreover we observe that multilayer networks can stabilize the fully controllable multiplex network configuration that can be stable also when the full controllability of the single network is not stable.

Systems medicine of inflammaging.

Systems Medicine (SM) can be defined as an extension of Systems Biology (SB) to Clinical-Epidemiological disciplines through a shifting paradigm, starting from a cellular, toward a patient centered framework. According to this vision, the three pillars of SM are Biomedical hypotheses, experimental data, mainly achieved by Omics technologies and tailored computational, statistical and modeling tools. The three SM pillars are highly interconnected, and their balancing is crucial. Despite the great technological progresses producing huge amount of data (Big Data) and impressive computational facilities, the Bio-Medical hypotheses are still of primary importance. A paradigmatic example of unifying Bio-Medical theory is the concept of Inflammaging. This complex phenotype is involved in a large number of pathologies and patho-physiological processes such as aging, age-related diseases and cancer, all sharing a common inflammatory pathogenesis. This Biomedical hypothesis can be mapped into an ecological perspective capable to describe by quantitative and predictive models some experimentally observed features, such as microenvironment, niche partitioning and phenotype propagation. In this article we show how this idea can be supported by computational methods useful to successfully integrate, analyze and model large data sets, combining cross-sectional and longitudinal information on clinical, environmental and omics data of healthy subjects and patients to provide new multidimensional biomarkers capable of distinguishing between different pathological conditions, e.g. healthy versus unhealthy state, physiological versus pathological aging.

Statistical strategies and stochastic predictive models for the MARK-AGE data.

MARK-AGE aims at the identification of biomarkers of human aging capable of discriminating between the chronological age and the effective functional status of the organism. To achieve this, given the structure of the collected data, a proper statistical analysis has to be performed, as the structure of the data are non trivial and the number of features under study is near to the number of subjects used, requiring special care to avoid overfitting. Here we described some of the possible strategies suitable for this analysis. We also include a description of the main techniques used, to explain and justify the selected strategies. Among other possibilities, we suggest to model and analyze the data with a three step strategy.

Emergent complex network geometry.

Networks are mathematical structures that are universally used to describe a large variety of complex systems such as the brain or the Internet. Characterizing the geometrical properties of these networks has become increasingly relevant for routing problems, inference and data mining. In real growing networks, topological, structural and geometrical properties emerge spontaneously from their dynamical rules. Nevertheless we still miss a model in which networks develop an emergent complex geometry. Here we show that a single two parameter network model, the growing geometrical network, can generate complex network geometries with non-trivial distribution of curvatures, combining exponential growth and small-world properties with finite spectral dimensionality. In one limit, the non-equilibrium dynamical rules of these networks can generate scale-free networks with clustering and communities, in another limit planar random geometries with non-trivial modularity. Finally we find that these properties of the geometrical growing networks are present in a large set of real networks describing biological, social and technological systems.