Dataset Information

Toxicology knowledge graph for structural birth defects.

ABSTRACT:

Background

Birth defects are functional and structural abnormalities that impact about 1 in 33 births in the United States. They have been attributed to genetic and other factors such as drugs, cosmetics, food, and environmental pollutants during pregnancy, but for most birth defects there are no known causes.

Methods

To further characterize associations between small molecule compounds and their potential to induce specific birth abnormalities, we gathered knowledge from multiple sources to construct a reproductive toxicity Knowledge Graph (ReproTox-KG) with a focus on associations between birth defects, drugs, and genes. Specifically, we gathered data from drug/birth-defect associations from co-mentions in published abstracts, gene/birth-defect associations from genetic studies, drug- and preclinical-compound-induced gene expression changes in cell lines, known drug targets, genetic burden scores for human genes, and placental crossing scores for small molecules.

Results

Using ReproTox-KG and semi-supervised learning (SSL), we scored >30,000 preclinical small molecules for their potential to cross the placenta and induce birth defects, and identified >500 birth-defect/gene/drug cliques that can be used to explain molecular mechanisms for drug-induced birth defects. The ReproTox-KG can be accessed via a web-based user interface available at https://maayanlab.cloud/reprotox-kg . This site enables users to explore the associations between birth defects, approved and preclinical drugs, and all human genes.

Conclusions

ReproTox-KG provides a resource for exploring knowledge about the molecular mechanisms of birth defects with the potential of predicting the likelihood of genes and preclinical small molecules to induce birth defects.

SUBMITTER: Evangelista JE

PROVIDER: S-EPMC10352311 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Toxicology knowledge graph for structural birth defects.

Evangelista John Erol JE Clarke Daniel J B DJB Xie Zhuorui Z Marino Giacomo B GB Utti Vivian V Jenkins Sherry L SL Ahooyi Taha Mohseni TM Bologa Cristian G CG Yang Jeremy J JJ Binder Jessica L JL Kumar Praveen P Lambert Christophe G CG Grethe Jeffrey S JS Wenger Eric E Taylor Deanne D Oprea Tudor I TI de Bono Bernard B Ma'ayan Avi A

Communications medicine 20230717 1

<h4>Background</h4>Birth defects are functional and structural abnormalities that impact about 1 in 33 births in the United States. They have been attributed to genetic and other factors such as drugs, cosmetics, food, and environmental pollutants during pregnancy, but for most birth defects there are no known causes.<h4>Methods</h4>To further characterize associations between small molecule compounds and their potential to induce specific birth abnormalities, we gathered knowledge from multiple ...[more]

PMID: 37460679

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Dataset Information

Toxicology knowledge graph for structural birth defects.

Background

Methods

Results

Conclusions

Publications

Toxicology knowledge graph for structural birth defects.

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