Local climate conditions play a major role in the biology of the Aedes aegypti mosquito, the main vector responsible for transmitting dengue, zika, chikungunya and yellow fever in urban centers. For this reason, a detailed assessment of periods in which changes in climate conditions affect the number of human cases may improve the timing of vector-control efforts. In this work, we develop new machine-learning algorithms to analyze climate time series and their connection to the occurrence of dengue epidemic years for seven Brazilian state capitals. Our method explores the impact of two key variables—frequency of precipitation and average temperature—during a wide range of time windows in the annual cycle. Our results indicate that each Brazilian state capital considered has its own climate signatures that correlate with the overall number of human dengue-cases. However, for most of the studied cities, the winter preceding an epidemic year shows a strong predictive power. Understanding such climate contributions to the vector’s biology could lead to more accurate prediction models and early warning systems.

Determining the interactions and causal relationships between nodes in an unknown networked dynamical system from measurement data alone is a challenging, contemporary task across the physical, biological, and engineering sciences. Statistical methods, such as the increasingly popular Granger causality, are being broadly applied for data-driven discovery of connectivity in fields from economics to neuroscience. A common version of the algorithm is called pairwise-conditional Granger causality, which we systematically test on data generated from a nonlinear model with known causal network structure. Specifically, we simulate networked systems of Kuramoto oscillators and use the Multivariate Granger Causality Toolbox to discover the underlying coupling structure of the system. We compare the inferred results to the original connectivity for a wide range of parameters such as initial conditions, connection strengths, community structures, and natural frequencies. Our results show a significant systematic disparity between the original and inferred network, unless the true structure is extremely sparse or dense. Specifically, the inferred networks have significant discrepancies in the number of edges and the eigenvalues of the connectivity matrix, demonstrating that they typically generate dynamics which are inconsistent with the ground truth. We provide a detailed account of the dynamics for the Erdős-Rényi network model due to its importance in random graph theory and network science. We conclude that Granger causal methods for inferring network structure are highly suspect and should always be checked against a ground truth model. The results also advocate the need to perform such comparisons with any network inference method since the inferred connectivity results appear to have very little to do with the ground truth system.

Alzheimer’s disease, the most common form of dementia, is characterized by the emergence and spread of senile plaques and neurofibrillary tangles, causing widespread neurodegeneration. Though the progression of Alzheimer’s disease is considered to be stereotyped, the significant variability within clinical populations obscures this interpretation on the individual level. Of particular clinical importance is understanding where exactly pathology, e.g. tau, emerges in each patient and how the incipient atrophy pattern relates to future spread of disease. Here we demonstrate a newly developed graph theoretical method of inferring prior disease states in patients with Alzheimer’s disease and mild cognitive impairment using an established network diffusion model and an L₁-penalized optimization algorithm. Although the ‘seeds’ of origin using our inference method successfully reproduce known trends in Alzheimer’s disease staging on a population level, we observed that the high degree of heterogeneity between patients at baseline is also reflected in their seeds. Additionally, the individualized seeds are significantly more predictive of future atrophy than a single seed placed at the hippocampus. Our findings illustrate that understanding where disease originates in individuals is critical to determining how it progresses and that our method allows us to infer early stages of disease from atrophy patterns observed at diagnosis.