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Advances in high-throughput technologies have enhanced our ability to describe microbial communities as they relate to human health and disease. Alongside the growth in sequencing data has come an influx of resources that synthesize knowledge surrounding microbial traits, functions, and metabolic potential with knowledge of how they may impact host pathways to influence disease phenotypes. These knowledge bases can enable the development of mechanistic explanations that may underlie correlations detected between microbial communities and disease. In this review, we survey existing resources and methodologies for the computational integration of broad classes of microbial and host knowledge. We evaluate these knowledge bases in their access methods, content, and source characteristics. We discuss challenges of the creation and utilization of knowledge bases including inconsistency of nomenclature assignment of taxa and metabolites across sources, whether the biological entities represented are rooted in ontologies or taxonomies, and how the structure and accessibility limit the diversity of applications and user types. We make this information available in a code and data repository at:https://github.com/lozuponelab/knowledge-source-mappings. Addressing these challenges will allow for the development of more effective tools for drawing from abundant knowledge to find new insights into microbial mechanisms in disease by fostering a systematic and unbiased exploration of existing information. 

Objectives We aim to estimate geographic variability in total numbers of infections and infection fatality ratios (IFR; the number of deaths caused by an infection per 1,000 infected people) when the availability and quality of data on disease burden are limited during an epidemic. Methods We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek testing. We demonstrate the robustness, accuracy, and precision of this framework, and apply it to the United States (U.S.) COVID-19 pandemic to estimate county-level SARS-CoV-2 IFRs. Results The estimators for the numbers of infections and IFRs showed high accuracy and precision; for instance, when applied to simulated validation data sets, across counties, Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928, respectively, and they showed strong robustness to model misspecification. Applying the county-level estimators to the real, unsimulated COVID-19 data spanning April 1, 2020 to September 30, 2020 from across the U.S., we found that IFRs varied from 0 to 44.69, with a standard deviation of 3.55 and a median of 2.14. Conclusions The proposed estimation framework can be used to identify geographic variation in IFRs across settings. 

Microbiome samples are inherently defined by the environment in which they are found. Therefore, data that provide context and enable interpretation of measurements produced from biological samples, often referred to as metadata, are critical.