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Evaluation of the health impacts of the 1990 Clean Air Act Amendments using causal inference and machine learning.

ABSTRACT: We develop a causal inference approach to estimate the number of adverse health events that were prevented due to changes in exposure to multiple pollutants attributable to a large-scale air quality intervention/regulation, with a focus on the 1990 Clean Air Act Amendments (CAAA). We introduce a causal estimand called the Total Events Avoided (TEA) by the regulation, defined as the difference in the number of health events expected under the no-regulation pollution exposures and the number observed with-regulation. We propose matching and machine learning methods that leverage population-level pollution and health data to estimate the TEA. Our approach improves upon traditional methods for regulation health impact analyses by formalizing causal identifying assumptions, utilizing population-level data, minimizing parametric assumptions, and collectively analyzing multiple pollutants. To reduce model-dependence, our approach estimates cumulative health impacts in the subset of regions with projected no-regulation features lying within the support of the observed with-regulation data, thereby providing a conservative but data-driven assessment to complement traditional parametric approaches. We analyze the health impacts of the CAAA in the US Medicare population in the year 2000, and our estimates suggest that large numbers of cardiovascular and dementia-related hospitalizations were avoided due to CAAA-attributable changes in pollution exposure.

SUBMITTER: Nethery RC

PROVIDER: S-EPMC7788006 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We previously developed EFICAz, an enzyme function inference approach that combines predictions from non-completely overlapping component methods. Two of the four components in the original EFICAz are based on the detection of functionally discriminating residues (FDRs). FDRs distinguish between member of an enzyme family that are homofunctional (classified under the EC number of interest) or heterofunctional (annotated with another EC number or lacking enzymatic activity). Each of the two FDR-based components is associated to one of two specific kinds of enzyme families. EFICAz exhibits high precision performance, except when the maximal test to training sequence identity (MTTSI) is lower than 30%. To improve EFICAz's performance in this regime, we: i) increased the number of predictive components and ii) took advantage of consensual information from the different components to make the final EC number assignment.We have developed two new EFICAz components, analogs to the two FDR-based components, where the discrimination between homo and heterofunctional members is based on the evaluation, via Support Vector Machine models, of all the aligned positions between the query sequence and the multiple sequence alignments associated to the enzyme families. Benchmark results indicate that: i) the new SVM-based components outperform their FDR-based counterparts, and ii) both SVM-based and FDR-based components generate unique predictions. We developed classification tree models to optimally combine the results from the six EFICAz components into a final EC number prediction. The new implementation of our approach, EFICAz2, exhibits a highly improved prediction precision at MTTSI < 30% compared to the original EFICAz, with only a slight decrease in prediction recall. A comparative analysis of enzyme function annotation of the human proteome by EFICAz2 and KEGG shows that: i) when both sources make EC number assignments for the same protein sequence, the assignments tend to be consistent and ii) EFICAz2 generates considerably more unique assignments than KEGG.Performance benchmarks and the comparison with KEGG demonstrate that EFICAz2 is a powerful and precise tool for enzyme function annotation, with multiple applications in genome analysis and metabolic pathway reconstruction. The EFICAz2 web service is available at: http://cssb.biology.gatech.edu/skolnick/webservice/EFICAz2/index.html.

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Evaluation of the health impacts of the 1990 Clean Air Act Amendments using causal inference and machine learning.

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