Dataset Information

A Method for Identifying Prevalent Chemical Combinations in the U.S. Population.

ABSTRACT:

Background

Through the food and water they ingest, the air they breathe, and the consumer products with which they interact at home and at work, humans are exposed to tens of thousands of chemicals, many of which have not been evaluated to determine their potential toxicities. Furthermore, while current chemical testing tends to focus on individual chemicals, the exposures that people actually experience involve mixtures of chemicals. Unfortunately, the number of mixtures that can be formed from the thousands of environmental chemicals is enormous, and testing all of them would be impossible.

Objectives

We seek to develop and demonstrate a method for identifying those mixtures that are most prevalent in humans.

Methods

We applied frequent itemset mining, a technique traditionally used for market basket analysis, to biomonitoring data from the 2009-2010 cycle of the continuous National Health and Nutrition Examination Survey (NHANES) to identify combinations of chemicals that frequently co-occur in people.

Results

We identified 90 chemical combinations consisting of relatively few chemicals that occur in at least 30% of the U.S. population, as well as three supercombinations consisting of relatively many chemicals that occur in a small but nonnegligible proportion of the U.S. population.

Conclusions

We demonstrated how FIM can be used in conjunction with biomonitoring data to narrow a large number of possible chemical combinations down to a smaller set of prevalent chemical combinations. https://doi.org/10.1289/EHP1265.

SUBMITTER: Kapraun DF

PROVIDER: S-EPMC5801475 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

A Method for Identifying Prevalent Chemical Combinations in the U.S. Population.

Kapraun Dustin F DF Wambaugh John F JF Ring Caroline L CL Tornero-Velez Rogelio R Setzer R Woodrow RW

Environmental health perspectives 20170824 8

<h4>Background</h4>Through the food and water they ingest, the air they breathe, and the consumer products with which they interact at home and at work, humans are exposed to tens of thousands of chemicals, many of which have not been evaluated to determine their potential toxicities. Furthermore, while current chemical testing tends to focus on individual chemicals, the exposures that people actually experience involve mixtures of chemicals. Unfortunately, the number of mixtures that can be for ...[more]

PMID: 28858827

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Project description:BackgroundAn important emerging trend in the analysis of microarray data is to incorporate known pathway information a priori. Expression level "summaries" for pathways, obtained from the expression data for the genes constituting the pathway, permit the inclusion of pathway information, reduce the high dimensionality of microarray data, and have the power to elucidate gene-interaction dependencies which are not already accounted for through known pathway identification.ResultsWe present a novel method for the analysis of microarray data that identifies joint differential expression in gene-pathway pairs. This method takes advantage of known gene pathway memberships to compute a summary expression level for each pathway as a whole. Correlations between the pathway expression summary and the expression levels of genes not already known to be associated with the pathway provide clues to gene interaction dependencies that are not already accounted for through known pathway identification, and statistically significant differences between gene-pathway correlations in phenotypically different cells (e.g., where the expression level of a single gene and a given pathway summary correlate strongly in normal cells but weakly in tumor cells) may indicate biologically relevant gene-pathway interactions. Here, we detail the methodology and present the results of this method applied to two gene-expression datasets, identifying gene-pathway pairs which exhibit differential joint expression by phenotype.ConclusionThe method described herein provides a means by which interactions between large numbers of genes may be identified by incorporating known pathway information to reduce the dimensionality of gene interactions. The method is efficient and easily applied to data sets of ~102 arrays. Application of this method to two publicly-available cancer data sets yields suggestive and promising results. This method has the potential to complement gene-at-a-time analysis techniques for microarray analysis by indicating relationships between pathways and genes that have not previously been identified and which may play a role in disease.

Project description:Biomarkers associated with treatment-effect heterogeneity can be used to make treatment recommendations that optimize individual clinical outcomes. To accomplish this, statistical methods are needed to generate marker-based treatment-selection rules that can most effectively reduce the population burden due to disease and treatment. Compared to the standard approach of risk modeling to derive treatment-selection rules, a more robust approach is to directly minimize an unbiased estimate of total disease and treatment burden among a pre-specified class of rules. This problem is one of minimizing a weighted sum of 0-1 loss function, which is computationally challenging to solve due to the nonsmoothness of 0-1 loss. Huang and Fong, among others, proposed a method that uses the Ramp loss to approximate the 0-1 loss and solves the minimization problem through repetitive constrained optimizations. The algorithm was shown to have comparable or better performance than other comparative estimators in various settings. Our aim in this article is to further extend the algorithm to allow for variable selection in the presence of a large number of candidate markers.We develop an alternative method to derive marker combinations to minimize the weighted sum of Ramp loss in Huang and Fong, based on data from randomized trials. The new algorithm estimates treatment-selection rules by repetitively minimizing a smooth and differentiable objective function. Through the use of an L1 penalty, we expand the method to allow for feature selection and develop an algorithm based on the coordinate descent method to build the treatment-selection rule.Through extensive simulation studies, we compared performance of the proposed estimator to four existing approaches: (1) a logistic regression risk modeling approach, and three other "direct optimizing" approaches including (2) the estimator in Huang and Fong, (3) the weighted support vector machine, and (4) the weighted logistic regression. The proposed estimator performs comparably to that of Huang and Fong, and comparably or better than other estimators. Allowing for variable selection using the proposed estimator in the presence of a large number of markers further improves treatment-selection performance. The proposed estimator is also advantageous for selecting variables relevant to treatment selection compared to L1 penalized logistic regression and weighted logistic regression. We illustrate the application of the proposed methods in host-genetics data from an HIV vaccine trial.The proposed estimator is appealing considering its effectiveness and conceptual simplicity. It has significant potential to contribute to the selection and combination of biomarkers for treatment selection in clinical practice.

Dataset Information

A Method for Identifying Prevalent Chemical Combinations in the U.S. Population.

Background

Objectives

Methods

Results

Conclusions

Publications

A Method for Identifying Prevalent Chemical Combinations in the U.S. Population.

Similar Datasets

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