Nonparametric Bayesian grouping methods for spatial time-series data

We describe an approach for identifying groups of dynamically similar locations in spatial time-series data based on a simple Markov transition model. We give maximum-likelihood, empirical Bayes, and fully Bayesian formulations of the model, and describe exhaustive, greedy, and MCMC-based inference methods. The approach has been employed successfully in several studies to reveal meaningful relationships between environmental patterns and disease dynamics.Comment: 11 pages, no figure

Homology blocks of Plasmodium falciparum var genes and clinically distinct forms of severe malaria in a local population

Abstract Background The primary target of the human immune response to the malaria parasite Plasmodium falciparum, P. falciparum erythrocyte membrane protein 1 (PfEMP1), is encoded by the members of the hyper-diverse var gene family. The parasite exhibits antigenic variation via mutually exclusive expression (switching) of the ~60 var genes within its genome. It is thought that different variants exhibit different host endothelial binding preferences that in turn result in different manifestations of disease. Results Var sequences comprise ancient sequence fragments, termed homology blocks (HBs), that recombine at exceedingly high rates. We use HBs to define distinct var types within a local population. We then reanalyze a dataset that contains clinical and var expression data to investigate whether the HBs allow for a description of sequence diversity corresponding to biological function, such that it improves our ability to predict disease phenotype from parasite genetics. We find that even a generic set of HBs, which are defined for a small number of non-local parasites: capture the majority of local sequence diversity; improve our ability to predict disease severity from parasite genetics; and reveal a previously hypothesized yet previously unobserved parasite genetic basis for two forms of severe disease. We find that the expression rates of some HBs correlate more strongly with severe disease phenotypes than the expression rates of classic var DBLα tag types, and principal components of HB expression rate profiles further improve genotype-phenotype models. More specifically, within the large Kenyan dataset that is the focus of this study, we observe that HB expression differs significantly for severe versus mild disease, and for rosetting versus impaired consciousness associated severe disease. The analysis of a second much smaller dataset from Mali suggests that these HB-phenotype associations are consistent across geographically distant populations, since we find evidence suggesting that the same HB-phenotype associations characterize this population as well. Conclusions The distinction between rosetting versus impaired consciousness associated var genes has not been described previously, and it could have important implications for monitoring, intervention and diagnosis. Moreover, our results have the potential to illuminate the molecular mechanisms underlying the complex spectrum of severe disease phenotypes associated with malaria—an important objective given that only about 1% of P. falciparum infections result in severe disease.http://deepblue.lib.umich.edu/bitstream/2027.42/112650/1/12866_2013_Article_2116.pd

Seasonality in the migration and establishment of H3N2 Influenza lineages with epidemic growth and decline

Background: Influenza A/H3N2 has been circulating in humans since 1968, causing considerable morbidity and mortality. Although H3N2 incidence is highly seasonal, how such seasonality contributes to global phylogeographic migration dynamics has not yet been established. Results: Incorporating seasonally varying migration rates improves the modeling of migration. In our global model, windows of increased immigration map to the seasonal timing of epidemic spread, while windows of increased emigration map to epidemic decline. Seasonal patterns also correlate with the probability that local lineages go extinct and fail to contribute to long term viral evolution, as measured through the trunk of the phylogeny. However, the fraction of the trunk in each community was found to be better determined by its overall human population size Conclusions: Seasonal migration and rapid turnover within regions is sustained by the invasion of 'fertile epidemic grounds' at the end of older epidemics. Thus, the current emphasis on connectivity, including air-travel, should be complemented with a better understanding of the conditions and timing required for successful establishment.Models which account for migration seasonality will improve our understanding of the seasonal drivers of influenza,enhance epidemiological predictions, and ameliorate vaccine updating by identifying strains that not only escape immunity but also have the seasonal opportunity to establish and spread. Further work is also needed on additional conditions that contribute to the persistence and long term evolution of influenza within the human population,such as spatial heterogeneity with respect to climate and seasonalityComment: in BMC Evolutionary Biology 2014, 1

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships in an ecosystem, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. A standard approach in food-web analysis, and network analysis in general, has been to identify compartments, or modules, defined by many links within compartments and few links between them. This approach can identify large habitat boundaries in the network but may fail to identify other important structures. Empirical analyses of food webs have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure using a flexible definition that can describe both functional trophic roles and standard compartments. We apply this method to a newly compiled plant-mammal food web from the Serengeti ecosystem that includes high taxonomic resolution at the plant level, allowing a simultaneous examination of the signature of both habitat and trophic roles in network structure. We find that groups at the plant level reflect habitat structure, coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial pattern, in contrast to the standard compartments typically identified. The network topology supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence. Furthermore, our Bayesian approach provides a powerful, flexible framework for the study of network structure, and we believe it will prove instrumental in a variety of biological contexts.</p

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

Estimating uncertainty in ecosystem budget calculations

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial License. The definitive version was published in Ecosystems 13 (2010): 239-248, doi:10.1007/s10021-010-9315-8.Ecosystem nutrient budgets often report values for pools and fluxes without any indication of uncertainty, which makes it difficult to evaluate the significance of findings or make comparisons across systems. We present an example, implemented in Excel, of a Monte Carlo approach to estimating error in calculating the N content of vegetation at the Hubbard Brook Experimental Forest in New Hampshire. The total N content of trees was estimated at 847 kg ha−1 with an uncertainty of 8%, expressed as the standard deviation divided by the mean (the coefficient of variation). The individual sources of uncertainty were as follows: uncertainty in allometric equations (5%), uncertainty in tissue N concentrations (3%), uncertainty due to plot variability (6%, based on a sample of 15 plots of 0.05 ha), and uncertainty due to tree diameter measurement error (0.02%). In addition to allowing estimation of uncertainty in budget estimates, this approach can be used to assess which measurements should be improved to reduce uncertainty in the calculated values. This exercise was possible because the uncertainty in the parameters and equations that we used was made available by previous researchers. It is important to provide the error statistics with regression results if they are to be used in later calculations; archiving the data makes resampling analyses possible for future researchers. When conducted using a Monte Carlo framework, the analysis of uncertainty in complex calculations does not have to be difficult and should be standard practice when constructing ecosystem budgets

Practical considerations for measuring the effective reproductive number, Rt.

Estimation of the effective reproductive number Rt is important for detecting changes in disease transmission over time. During the Coronavirus Disease 2019 (COVID-19) pandemic, policy makers and public health officials are using Rt to assess the effectiveness of interventions and to inform policy. However, estimation of Rt from available data presents several challenges, with critical implications for the interpretation of the course of the pandemic. The purpose of this document is to summarize these challenges, illustrate them with examples from synthetic data, and, where possible, make recommendations. For near real-time estimation of Rt, we recommend the approach of Cori and colleagues, which uses data from before time t and empirical estimates of the distribution of time between infections. Methods that require data from after time t, such as Wallinga and Teunis, are conceptually and methodologically less suited for near real-time estimation, but may be appropriate for retrospective analyses of how individuals infected at different time points contributed to the spread. We advise caution when using methods derived from the approach of Bettencourt and Ribeiro, as the resulting Rt estimates may be biased if the underlying structural assumptions are not met. Two key challenges common to all approaches are accurate specification of the generation interval and reconstruction of the time series of new infections from observations occurring long after the moment of transmission. Naive approaches for dealing with observation delays, such as subtracting delays sampled from a distribution, can introduce bias. We provide suggestions for how to mitigate this and other technical challenges and highlight open problems in Rt estimation

Limits to Causal Inference with State-Space Reconstruction for Infectious Disease

Infectious diseases are notorious for their complex dynamics, which make it difficult to fit models to test hypotheses. Methods based on state-space reconstruction have been proposed to infer causal interactions in noisy, nonlinear dynamical systems. These “model-free” methods are collectively known as convergent cross-mapping (CCM). Although CCM has theoretical support, natural systems routinely violate its assumptions. To identify the practical limits of causal inference under CCM, we simulated the dynamics of two pathogen strains with varying interaction strengths. The original method of CCM is extremely sensitive to periodic fluctuations, inferring interactions between independent strains that oscillate with similar frequencies. This sensitivity vanishes with alternative criteria for inferring causality. However, CCM remains sensitive to high levels of process noise and changes to the deterministic attractor. This sensitivity is problematic because it remains challenging to gauge noise and dynamical changes in natural systems, including the quality of reconstructed attractors that underlie cross-mapping. We illustrate these challenges by analyzing time series of reportable childhood infections in New York City and Chicago during the pre-vaccine era. We comment on the statistical and conceptual challenges that currently limit the use of state-space reconstruction in causal inference

Limits to Causal Inference with State-Space Reconstruction for Infectious Disease

<div><p>Infectious diseases are notorious for their complex dynamics, which make it difficult to fit models to test hypotheses. Methods based on state-space reconstruction have been proposed to infer causal interactions in noisy, nonlinear dynamical systems. These “model-free” methods are collectively known as convergent cross-mapping (CCM). Although CCM has theoretical support, natural systems routinely violate its assumptions. To identify the practical limits of causal inference under CCM, we simulated the dynamics of two pathogen strains with varying interaction strengths. The original method of CCM is extremely sensitive to periodic fluctuations, inferring interactions between independent strains that oscillate with similar frequencies. This sensitivity vanishes with alternative criteria for inferring causality. However, CCM remains sensitive to high levels of process noise and changes to the deterministic attractor. This sensitivity is problematic because it remains challenging to gauge noise and dynamical changes in natural systems, including the quality of reconstructed attractors that underlie cross-mapping. We illustrate these challenges by analyzing time series of reportable childhood infections in New York City and Chicago during the pre-vaccine era. We comment on the statistical and conceptual challenges that currently limit the use of state-space reconstruction in causal inference.</p></div

Interactions detected as a function of process noise and the strength of interaction (<i>C</i>₂ → <i>C</i>₁) and representative time series.

<p>Heat maps show the fraction of 100 replicates significant for each inferred interaction for different parameter combinations. A maximum, positive cross-map correlation <i>ρ</i> at a negative lag indicated a causal interaction. Each replicate used 100 years of monthly incidence.</p