Dataset Information

Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features.

ABSTRACT: In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high-throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation.

SUBMITTER: Huang R

PROVIDER: S-EPMC2777082 | biostudies-other | 2009 Dec

REPOSITORIES: biostudies-other

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Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features.

Huang Ruili R Southall Noel N Xia Menghang M Cho Ming-Hsuang MH Jadhav Ajit A Nguyen Dac-Trung DT Inglese James J Tice Raymond R RR Austin Christopher P CP

Toxicological sciences : an official journal of the Society of Toxicology 20091004 2

In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high-throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) data f ...[more]

PMID: 19805409

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Project description:In recent years, functional brain network topological features have been widely used as classification features. Previous studies have found that network node scale differences caused by different network parcellation definitions significantly affect the structure of the constructed network and its topological properties. However, we still do not know how network scale differences affect the classification accuracy, performance of classification features, and effectiveness of the feature selection strategy using P values in terms of the machine learning method. This study used five scale parcellations, involving 90, 256, 497, 1003, and 1501 nodes. Three local properties of resting-state functional brain networks were selected (degree, betweenness centrality, and nodal efficiency), and the support vector machine method was used to construct classifiers to identify patients with major depressive disorder. We analyzed the impact of the five scales on classification accuracy. In addition, the effectiveness and redundancy of features obtained by the different scale parcellations were compared. Finally, traditional statistical significance (P value) was verified as a feature selection criterion. The results showed that the feature effectiveness of different scales was similar; in other words, parcellation with more regions did not provide more effective discriminative features. Nevertheless, parcellation with more regions did provide a greater quantity of discriminative features, which led to an improvement in the accuracy of the classification. However, due to the close distance between brain regions, the redundancy of parcellation with more regions was also greater. The traditional P value feature selection strategy is feasible with different scales, but our analysis showed that the traditional P < 0.05 threshold was too strict for feature selection. This study provides an important reference for the selection of network scales when applying topological properties of brain networks to machine learning methods.

Dataset Information

Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features.

Publications

Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features.

Similar Datasets

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