Improving ADME Prediction with Multitask Graph Neural Networks and Assessing Explainability in Lead Optimization
Bibliographic record
Abstract
Early evaluation of absorption, distribution, metabolism, and excretion (ADME) properties is crucial for streamlining drug development. Traditional in vivo and in vitro approaches are often expensive. Moreover, during lead optimization, these methods rely heavily on the expertise of specialists, leading to efficiency challenges. Consequently, in silico methods for ADME prediction are attracting increasing attention. However, existing in silico methods face two major issues: a decline in predictive performance caused by limited ADME data and a lack of clarity regarding the rationale for lead optimization to improve ADME properties. In this study, we built an AI model capable of predicting ten different ADME parameters to overcome these challenges. Our training approach was based on a graph neural network combining multitask learning, which shares information across multiple tasks to increase the number of usable samples, with fine-tuning that adapts to each task. In addition, we applied the integrated gradients method to compound data collected before and after lead optimization to quantify and interpret each input feature's contribution to the predicted ADME values. Our proposed model achieved the highest performance for seven of the ten ADME parameters compared with conventional methods. Furthermore, visualization of the changes in chemical structures before and after lead optimization revealed that the model's explanations aligned well with established chemical insights. These results suggest that data-driven approaches may assist molecular design by providing complementary insights into empirical rules.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".