Characterizing the effects of missing data and evaluating imputation methods for chemical prioritization applications...

Area of Science:

• Environmental Science
• Toxicology
• Computational Chemistry

Background:

• The Toxicological Priority Index (ToxPi) is a chemical prioritization and profiling method integrating diverse data sources.
• Missing data in chemical assays (e.g., in vitro, in vivo) is common, where not all chemicals are tested in every assay.
• The Agency for Toxic Substances and Disease Registry's (ATSDR) Substance Priority List (SPL) identifies chemicals for environmental research and remediation.

Purpose of the Study:

• To investigate the effects of missing data on chemical prioritization using simulation studies.
• To evaluate various data imputation methods for addressing missing data in high-throughput screening (HTS) datasets.
• To recommend solutions for handling missing data in toxicological profiling.

Main Methods:

• Designed simulation studies using HTS data from ToxCast and Tox21 programs.
• Explored scenarios with varying percentages of missing assay data (0-80%) per chemical.
• Tested multiple imputation methods including k-Nearest-Neighbor (kNN), Singular Value Decomposition (SVD), Max, Mean, Min, Binomial, and Local Least Squares.

Main Results:

• Most imputation methods significantly altered ToxPi scores, except in datasets with few assays.
• Chemical ranks were found to be more sensitive to score changes with minimum value imputation, SVD imputation, and kNN imputation.
• The impact of imputation on scores and ranks was most pronounced in scenarios with fewer assays and higher proportions of missing data.

Conclusions:

• The choice of imputation strategy significantly influences chemical scores and their associated ranks in toxicological profiling.
• Understanding the effects of missing data and the performance of imputation methods is crucial for robust decision-making.
• Characterizing these effects enhances confidence in assessing the health and ecological impacts of environmental chemicals.