Dataset Information

Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions.

ABSTRACT: Genome-scale metabolic models provide a valuable context for analyzing data from diverse high-throughput experimental techniques. Models can quantify the activities of diverse pathways and cellular functions. Since some metabolic reactions are only catalyzed in specific environments, several algorithms exist that build context-specific models. However, these methods make differing assumptions that influence the content and associated predictive capacity of resulting models, such that model content varies more due to methods used than cell types. Here we overcome this problem with a novel framework for inferring the metabolic functions of a cell before model construction. For this, we curated a list of metabolic tasks and developed a framework to infer the activity of these functionalities from transcriptomic data. We protected the data-inferred tasks during the implementation of diverse context-specific model extraction algorithms for 44 cancer cell lines. We show that the protection of data-inferred metabolic tasks decreases the variability of models across extraction methods. Furthermore, resulting models better capture the actual biological variability across cell lines. This study highlights the potential of using biological knowledge, inferred from omics data, to obtain a better consensus between existing extraction algorithms. It further provides guidelines for the development of the next-generation of data contextualization methods.

SUBMITTER: Richelle A

PROVIDER: S-EPMC6483243 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions.

Richelle Anne A Chiang Austin W T AWT Kuo Chih-Chung CC Lewis Nathan E NE

PLoS computational biology 20190415 4

Genome-scale metabolic models provide a valuable context for analyzing data from diverse high-throughput experimental techniques. Models can quantify the activities of diverse pathways and cellular functions. Since some metabolic reactions are only catalyzed in specific environments, several algorithms exist that build context-specific models. However, these methods make differing assumptions that influence the content and associated predictive capacity of resulting models, such that model conte ...[more]

PMID: 30986217

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Project description:Movement behavior is an important contributor to habitat selection and its incorporation in disease risk models has been somewhat neglected. The habitat preferences of host individuals affect their probability of exposure to pathogens. If preference behavior can be incorporated in ecological niche models (ENMs) when data on pathogen distributions are available, then variation in such behavior may dramatically impact exposure risk. Here we use data from the anthrax endemic system of Etosha National Park, Namibia, to demonstrate how integrating inferred movement behavior alters the construction of disease risk maps. We used a Maximum Entropy (MaxEnt) model that associated soil, bioclimatic, and vegetation variables with the best available pathogen presence data collected at anthrax carcass sites to map areas of most likely Bacillus anthracis (the causative bacterium of anthrax) persistence. We then used a hidden Markov model (HMM) to distinguish foraging and non-foraging behavioral states along the movement tracks of nine zebra (Equus quagga) during the 2009 and 2010 anthrax seasons. The resulting tracks, decomposed on the basis of the inferred behavioral state, formed the basis of step-selection functions (SSFs) that used the MaxEnt output as a potential predictor variable. Our analyses revealed different risks of exposure during different zebra behavioral states, which were obscured when the full movement tracks were analyzed without consideration of the underlying behavioral states of individuals. Pathogen (or vector) distribution models may be misleading with regard to the actual risk faced by host animal populations when specific behavioral states are not explicitly accounted for in selection analyses. To more accurately evaluate exposure risk, especially in the case of environmentally transmitted pathogens, selection functions could be built for each identified behavioral state and then used to assess the comparative exposure risk across relevant states. The scale of data collection and analysis, however, introduces complexities and limitations for consideration when interpreting results.

Dataset Information

Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions.

Publications

Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions.

Similar Datasets

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