ArticleToxicological sciences : an official journal of the Society of Toxicology2018
In Silico Site-Directed Mutagenesis Informs Species-Specific Predictions of Chemical Susceptibility Derived From the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Weight of evidence for cross-species conservation of androgen receptor-based biological activity.Toxicological sciences : an official journal of the Society of Toxicology · 2023Pooled it
- Potential ofArhiv za higijenu rada i toksikologiju · 2026Article
- Article
- Quest for Orthologs in the era of Data Deluge and AI: Challenges and Innovations in Orthology Prediction and Data Integration.Journal of molecular evolution · 2025Review
- Continuous improvement towards environmental protection for pharmaceuticals: advancing a strategy for Europe.Environmental sciences Europe · 2025Review
- In vitro assessment of thyroid peroxidase inhibition by chemical exposure: comparison of cell models and detection methods.Archives of toxicology · 2024Article
- The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health.BMC genomics · 2023Review
- Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation.Journal of visualized experiments : JoVE · 2023Article
- Leveraging ToxCast data and protein sequence conservation to complement aquatic life criteria derivation.Integrated environmental assessment and management · 2023Article
- Defining the Biologically Plausible Taxonomic Domain of Applicability of an Adverse Outcome Pathway: A Case Study Linking Nicotinic Acetylcholine Receptor Activation to Colony Death.Environmental toxicology and chemistry · 2023Article
- Repertoire-scale measures of antigen binding.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Quantitative Chemical Proteomics Reveals Interspecies Variations on Binding Schemes of L-FABP with Perfluorooctanesulfonate.Environmental science & technology · 2021Article
- Integrative Computational Approaches to Inform Relative Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances Across Species.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Evaluation of a multiplexed, multispecies nuclear receptor assay for chemical hazard assessment.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- Conversion of Estrone to 17β-Estradiol: A Potential Confounding Factor in Assessing Risks of Environmental Estrogens to Fish.Environmental toxicology and chemistry · 2020Article
- Neuropathy target esterase (NTE/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN).Advances in neurotoxicology · 2020Article
- Adverse Outcome Pathways: Moving from a Scientific Concept to an Internationally Accepted Framework.Environmental toxicology and chemistry · 2019Article
- Homology models of mouse and rat estrogen receptor-Computational toxicology (Amsterdam, Netherlands) · 2019Article
- A unified approach for protecting listed species and ecosystem services in isolated wetlands using community-level protection goals.The Science of the total environment · 2019Article
- Evidence for Cross Species Extrapolation of Mammalian-Based High-Throughput Screening Assay Results.Environmental science & technology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Chemical hazard assessment requires extrapolation of information from model organisms to all species of concern. The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed as a rapid, cost-effective method to aid cross-species extrapolation of susceptibility to chemicals acting on specific protein targets through evaluation of protein structural similarities and differences. The greatest resolution for extrapolation of chemical susceptibility across species involves comparisons of individual amino acid residues at key positions involved in protein-chemical interactions. However, a lack of understanding of whether specific amino acid substitutions among species at key positions in proteins affect interaction with chemicals made manual interpretation of alignments time consuming and potentially inconsistent. Therefore, this study used in silico site-directed mutagenesis coupled with docking simulations of computational models for acetylcholinesterase (AChE) and ecdysone receptor (EcR) to investigate how specific amino acid substitutions impact protein-chemical interaction. This study found that computationally derived substitutions in identities of key amino acids caused no change in protein-chemical interaction if residues share the same side chain functional properties and have comparable molecular dimensions, while differences in these characteristics can change protein-chemical interaction. These findings were considered in the development of capabilities for automatically generated species-specific predictions of chemical susceptibility in SeqAPASS. These predictions for AChE and EcR were shown to agree with SeqAPASS predictions comparing the primary sequence and functional domain sequence of proteins for more than 90% of the investigated species, but also identified dramatic species-specific differences in chemical susceptibility that align with results from standard toxicity tests. These results provide a compelling line of evidence for use of SeqAPASS in deriving screening level, species-specific, susceptibility predictions across broad taxonomic groups for application to human and ecological hazard assessment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.