DILI-Context: A Dose- and Exposure-Enriched Knowledge Base for Translational Liver Safety Assessment
Clicks: 5
ID: 319147
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
1.2
/100
5 views
0 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #72 of 123 articles by views in toxicological sciences : an official journal of the society of toxicology
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 123 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Drug-induced liver injury (DILI) is a major cause of drug development failure and post-marketing withdrawal. While assessing clinical hepatotoxic risk is critical for decision-making, most benchmark datasets represent DILI with categorical hazard labels rather than exposure-dependent risk measures. As a result, the current understanding of DILI risk focuses on hazard rather than context-dependent exposure risk. To address this limitation, we present DILI-Context, a dose- and exposure-enriched knowledge base that integrates hazard annotations with high-content regulatory and toxicological data sources. This framework incorporates therapeutic dose, treatment duration, and preclinical safety thresholds to contextualize hepatotoxic liability. Using this harmonized resource, we observe a consistent monotonic relationship between therapeutic dose and DILI severity, with higher daily dose requirements associated with greater hepatotoxic concern. Our results show that drugs with elevated DILI risk operate within significantly narrower therapeutic windows, demonstrated by systematic declines in both acute Therapeutic Index and chronic Margin of Safety across DILI categories. We also demonstrate that chronic no-effect thresholds (NOAEL-based metrics) more effectively discriminate DILI risk than lowest-effect endpoints (LOAEL). To further capture cumulative burden, we introduce Chronic Load Score that integrates dose magnitude and treatment duration. This metric significantly stratifies DILI concern levels and aligns with independent regulatory signals, including hepatic dose adjustment requirements in prescribing information. Together, these findings demonstrate that hepatotoxic liability is strongly linked to required systemic exposure and constrained safety margins. We further characterize the chemical-property landscape of included small molecules and provide a minimalist benchmark comparing Morgan fingerprint-only classifiers against classifiers enriched with exposure-derived covariates, demonstrating complementary predictive signal beyond structure alone under the cohort constraints of DILIrank 2.0. **DILI-Context** thus provides both a reproducible supplementary feature layer and an explicit resource for advancing exposure-aware DILI modeling.
| Reference Key |
openalex_W7166556334
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Rohola Zandie, R Betancort, Farhan Khodaee |
| Journal | toxicological sciences : an official journal of the society of toxicology |
| Year | 2026 |
| DOI |
10.1093/toxsci/kfag077
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.