Most diseases disrupt multiple proteins, and drugs treat such diseases by restoring the functions of the disrupted proteins. How drugs restore these functions, however, is often unknown as a drug's ...therapeutic effects are not limited to the proteins that the drug directly targets. Here, we develop the multiscale interactome, a powerful approach to explain disease treatment. We integrate disease-perturbed proteins, drug targets, and biological functions into a multiscale interactome network. We then develop a random walk-based method that captures how drug effects propagate through a hierarchy of biological functions and physical protein-protein interactions. On three key pharmacological tasks, the multiscale interactome predicts drug-disease treatment, identifies proteins and biological functions related to treatment, and predicts genes that alter a treatment's efficacy and adverse reactions. Our results indicate that physical interactions between proteins alone cannot explain treatment since many drugs treat diseases by affecting the biological functions disrupted by the disease rather than directly targeting disease proteins or their regulators. We provide a general framework for explaining treatment, even when drugs seem unrelated to the diseases they are recommended for.
Underserved populations experience higher levels of pain. These disparities persist even after controlling for the objective severity of diseases like osteoarthritis, as graded by human physicians ...using medical images, raising the possibility that underserved patients' pain stems from factors external to the knee, such as stress. Here we use a deep learning approach to measure the severity of osteoarthritis, by using knee X-rays to predict patients' experienced pain. We show that this approach dramatically reduces unexplained racial disparities in pain. Relative to standard measures of severity graded by radiologists, which accounted for only 9% (95% confidence interval (CI), 3-16%) of racial disparities in pain, algorithmic predictions accounted for 43% of disparities, or 4.7× more (95% CI, 3.2-11.8×), with similar results for lower-income and less-educated patients. This suggests that much of underserved patients' pain stems from factors within the knee not reflected in standard radiographic measures of severity. We show that the algorithm's ability to reduce unexplained disparities is rooted in the racial and socioeconomic diversity of the training set. Because algorithmic severity measures better capture underserved patients' pain, and severity measures influence treatment decisions, algorithmic predictions could potentially redress disparities in access to treatments like arthroplasty.
An unhealthy diet is a major risk factor for chronic diseases including cardiovascular disease, type 2 diabetes, and cancer
. Limited access to healthy food options may contribute to unhealthy diets
.... Studying diets is challenging, typically restricted to small sample sizes, single locations, and non-uniform design across studies, and has led to mixed results on the impact of the food environment
. Here we leverage smartphones to track diet health, operationalized through the self-reported consumption of fresh fruits and vegetables, fast food and soda, as well as body-mass index status in a country-wide observational study of 1,164,926 U.S. participants (MyFitnessPal app users) and 2.3 billion food entries to study the independent contributions of fast food and grocery store access, income and education to diet health outcomes. This study constitutes the largest nationwide study examining the relationship between the food environment and diet to date. We find that higher access to grocery stores, lower access to fast food, higher income and college education are independently associated with higher consumption of fresh fruits and vegetables, lower consumption of fast food and soda, and lower likelihood of being affected by overweight and obesity. However, these associations vary significantly across zip codes with predominantly Black, Hispanic or white populations. For instance, high grocery store access has a significantly larger association with higher fruit and vegetable consumption in zip codes with predominantly Hispanic populations (7.4% difference) and Black populations (10.2% difference) in contrast to zip codes with predominantly white populations (1.7% difference). Policy targeted at improving food access, income and education may increase healthy eating, but intervention allocation may need to be optimized for specific subpopulations and locations.
The coronavirus disease 2019 (COVID-19) pandemic markedly changed human mobility patterns, necessitating epidemiological models that can capture the effects of these changes in mobility on the spread ...of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
. Here we introduce a metapopulation susceptible-exposed-infectious-removed (SEIR) model that integrates fine-grained, dynamic mobility networks to simulate the spread of SARS-CoV-2 in ten of the largest US metropolitan areas. Our mobility networks are derived from mobile phone data and map the hourly movements of 98 million people from neighbourhoods (or census block groups) to points of interest such as restaurants and religious establishments, connecting 56,945 census block groups to 552,758 points of interest with 5.4 billion hourly edges. We show that by integrating these networks, a relatively simple SEIR model can accurately fit the real case trajectory, despite substantial changes in the behaviour of the population over time. Our model predicts that a small minority of 'superspreader' points of interest account for a large majority of the infections, and that restricting the maximum occupancy at each point of interest is more effective than uniformly reducing mobility. Our model also correctly predicts higher infection rates among disadvantaged racial and socioeconomic groups
solely as the result of differences in mobility: we find that disadvantaged groups have not been able to reduce their mobility as sharply, and that the points of interest that they visit are more crowded and are therefore associated with higher risk. By capturing who is infected at which locations, our model supports detailed analyses that can inform more-effective and equitable policy responses to COVID-19.
Higher-order organization of complex networks Benson, Austin R.; Gleich, David F.; Leskovec, Jure
Science (American Association for the Advancement of Science),
07/2016, Letnik:
353, Številka:
6295
Journal Article
Recenzirano
Odprti dostop
Networks are a fundamental tool for understanding and modeling complex systems in physics, biology, neuroscience, engineering, and social science. Many networks are known to exhibit rich, lower-order ...connectivity patterns that can be captured at the level of individual nodes and edges. However, higher-order organization of complex networks—at the level of small network subgraphs—remains largely unknown. Here, we develop a generalized framework for clustering networks on the basis of higher-order connectivity patterns. This framework provides mathematical guarantees on the optimality of obtained clusters and scales to networks with billions of edges. The framework reveals higher-order organization in a number of networks, including information propagation units in neuronal networks and hub structure in transportation networks. Results show that networks exhibit rich higher-order organizational structures that are exposed by clustering based on higher-order connectivity patterns.
Uncovering modular structure in networks is fundamental for systems in biology, physics, and engineering. Community detection identifies candidate modules as hypotheses, which then need to be ...validated through experiments, such as mutagenesis in a biological laboratory. Only a few communities can typically be validated, and it is thus important to prioritize which communities to select for downstream experimentation. Here we develop CRANK, a mathematically principled approach for prioritizing network communities. CRANK efficiently evaluates robustness and magnitude of structural features of each community and then combines these features into the community prioritization. CRANK can be used with any community detection method. It needs only information provided by the network structure and does not require any additional metadata or labels. However, when available, CRANK can incorporate domain-specific information to further boost performance. Experiments on many large networks show that CRANK effectively prioritizes communities, yielding a nearly 50-fold improvement in community prioritization.
To be able to curb the global pandemic of physical inactivity and the associated 5.3 million deaths per year, we need to understand the basic principles that govern physical activity. However, there ...is a lack of large-scale measurements of physical activity patterns across free-living populations worldwide. Here we leverage the wide usage of smartphones with built-in accelerometry to measure physical activity at the global scale. We study a dataset consisting of 68 million days of physical activity for 717,527 people, giving us a window into activity in 111 countries across the globe. We find inequality in how activity is distributed within countries and that this inequality is a better predictor of obesity prevalence in the population than average activity volume. Reduced activity in females contributes to a large portion of the observed activity inequality. Aspects of the built environment, such as the walkability of a city, are associated with a smaller gender gap in activity and lower activity inequality. In more walkable cities, activity is greater throughout the day and throughout the week, across age, gender, and body mass index (BMI) groups, with the greatest increases in activity found for females. Our findings have implications for global public health policy and urban planning and highlight the role of activity inequality and the built environment in improving physical activity and health.
Phenotype robustness to environmental fluctuations is a common biological phenomenon. Although most phenotypes involve multiple proteins that interact with each other, the basic principles of how ...such interactome networks respond to environmental unpredictability and change during evolution are largely unknown. Here we study interactomes of 1,840 species across the tree of life involving a total of 8,762,166 protein–protein interactions. Our study focuses on the resilience of interactomes to network failures and finds that interactomes become more resilient during evolution, meaning that interactomes become more robust to network failures over time. In bacteria, we find that a more resilient interactome is in turn associated with the greater ability of the organism to survive in a more complex, variable, and competitive environment. We find that at the protein family level proteins exhibit a coordinated rewiring of interactions over time and that a resilient interactome arises through gradual change of the network topology. Our findings have implications for understanding molecular network structure in the context of both evolution and environment.
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