Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression

Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable...

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Published in:Environmental health Vol. 17; no. 1; pp. 67 - 10
Main Authors: Bobb, Jennifer F., Claus Henn, Birgit, Valeri, Linda, Coull, Brent A.
Format: Journal Article
Language:English
Published: London BioMed Central 20.08.2018
BioMed Central Ltd
Springer Nature B.V
BMC
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ISSN:1476-069X, 1476-069X
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Abstract Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. Methods This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Results Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. Conclusions This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
AbstractList Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. Methods This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Results Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. Conclusions This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
Abstract Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. Methods This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Results Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. Conclusions This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. Methods This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Results Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. Conclusions This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health. Keywords: Multiple exposures, Mixtures, Exposure-response, Variable selection, Health risk estimation
Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables. Methods This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code. Results Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability. Conclusions This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables.BACKGROUNDEstimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the health effects of mixtures, Bayesian kernel machine regression (BKMR), has been developed. This method estimates the multivariable exposure-response function in a flexible and parsimonious way, conducts variable selection on the (potentially high-dimensional) vector of exposures, and allows for a grouped variable selection approach that can accommodate highly correlated exposures. However, the application of this novel method has been limited by a lack of available software, the need to derive interpretable output in a computationally efficient manner, and the inability to apply the method to non-continuous outcome variables.This paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code.METHODSThis paper addresses these limitations by (i) introducing an open-source software package in the R programming language, the bkmr R package, (ii) demonstrating methods for visualizing high-dimensional exposure-response functions, and for estimating scientifically relevant summaries, (iii) illustrating a probit regression implementation of BKMR for binary outcomes, and (iv) describing a fast version of BKMR that utilizes a Gaussian predictive process approach. All of the methods are illustrated using fully reproducible examples with the provided R code.Applying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability.RESULTSApplying the methods to a continuous outcome example illustrated the ability of the BKMR implementation to estimate the health effects of multi-pollutant mixtures in the context of a highly nonlinear, biologically-based dose-response function, and to estimate overall, single-exposure, and interactive health effects. The Gaussian predictive process method led to a substantial reduction in the runtime, without a major decrease in accuracy. In the setting of a larger number of exposures and a dichotomous outcome, the probit BKMR implementation was able to correctly identify the variables included in the exposure-response function and yielded interpretable quantities on the scale of a latent continuous outcome or on the scale of the outcome probability.This newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.CONCLUSIONSThis newly developed software, integrated suite of tools, and extended methodology makes BKMR accessible for use across a broad range of epidemiological applications in which multiple risk factors have complex effects on health.
ArticleNumber 67
Audience Academic
Author Bobb, Jennifer F.
Coull, Brent A.
Claus Henn, Birgit
Valeri, Linda
Author_xml – sequence: 1
  givenname: Jennifer F.
  surname: Bobb
  fullname: Bobb, Jennifer F.
  email: jennifer.f.bobb@kp.org
  organization: Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Department of Biostatistics, University of Washington
– sequence: 2
  givenname: Birgit
  surname: Claus Henn
  fullname: Claus Henn, Birgit
  organization: Department of Environmental Health, Boston University School of Public Health
– sequence: 3
  givenname: Linda
  surname: Valeri
  fullname: Valeri, Linda
  organization: Psychiatric Biostatistics Laboratory, McLean Hospital
– sequence: 4
  givenname: Brent A.
  surname: Coull
  fullname: Coull, Brent A.
  organization: Department of Biostatistics, Harvard T H Chan School of Public Health
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30126431$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Exposure-response
Mixtures
Health risk estimation
Multiple exposures
Variable selection
Language English
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Snippet Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for...
Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for estimating the...
Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach for...
Abstract Background Estimating the health effects of multi-pollutant mixtures is of increasing interest in environmental epidemiology. Recently, a new approach...
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SubjectTerms Air pollution
Bayes Theorem
Bayesian analysis
Computer programs
Continuity (mathematics)
Dose-response effects
Earth and Environmental Science
Environment
Environmental Epidemiology
Environmental Exposure - adverse effects
Environmental Health
Environmental Health - methods
Environmental Monitoring - methods
Environmental Pollutants - adverse effects
Epidemiology
Estimation
Exposure
Exposure-response
Gaussian process
Health
Health aspects
Health risk estimation
Medical research
Methodology
Mixtures
Models, Statistical
Multiple exposures
Nonlinear response
Occupational Medicine/Industrial Medicine
Open source software
Organic chemicals
Pollutants
Pollution
Principal components analysis
Programming languages
Public Health
Regression analysis
Response functions
Risk analysis
Risk factors
Simulation
Software
Source code
Statistical analysis
Statistical methods
Statistical software
Variable selection
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Title Statistical software for analyzing the health effects of multiple concurrent exposures via Bayesian kernel machine regression
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