The study evaluates how different molecular feature spaces—Morgan fingerprints, RDKit physicochemical descriptors, and SMILES bigrams—affect the prediction of blood‑brain barrier permeability using various learning algorithms. Dynamic Random Forests with combined features achieved the best performance (mean AUC 0.970). When applying Generalized Random Forests to estimate heterogeneous effects of LogP on BBB permeability, orthogonalization revealed that apparent heterogeneity largely vanished after accounting for confounding, shifting importance toward residual SMILES bigram information.
arXiv:2608. 04257v1 Announce Type: new Abstract: Blood-brain barrier permeability (BBBP) prediction is a critical screening task in central nervous system drug discovery, where candidate molecules must be assessed for whether they can cross, or should be prevented from crossing, the blood-brain barrier.
The paper introduces a new algorithm that uses decision trees and random forests to estimate individual treatment effects while providing interpretability. It modifies the standard random forest splitting criterion by combining a heterogeneity-focused criterion with a bias-correction criterion, enabling the model to handle observational studies with varying treatment propensities without separately estimating propensity scores. The resulting tree structure directly reveals which features drive treatment effect differences, and simulation studies show the method matches or surpasses existing approaches in prediction accuracy while improving interpretability.
arXiv:2608. 11444v1 Announce Type: cross Abstract: Drug response prediction (DRP) models are an active area of research in pharmacogenomics, with growing potential to accelerate the identification of effective anticancer drugs.
arXiv:2606. 08973v1 Announce Type: cross Abstract: Fundamental investigations into how different molecular encoding methods affect molecular property prediction remain relatively limited.
arXiv:2603. 02221v2 Announce Type: replace-cross Abstract: In clinical tabular prediction, classical machine learning models with feature engineering often outperform neural methods.
Monroe is a new molecular foundation model that improves upon existing models by pre‑training on over 81 million molecules from the PM6 quantum chemistry dataset, enhancing stereochemistry representation, and introducing novel training losses such as conformer denoising and embedding decorrelation. It also incorporates a prior‑data‑fitted model (TabPFN) for downstream in‑context prediction and demonstrates superior performance on Polaris benchmarks and activity cliff tests. Ablation studies show that the PFN‑based downstream approach can upgrade other models, producing state‑of‑the‑art variants MiniMol_PFN and CheMeleon_PFN.
ProbeMatchDTI introduces a probe-driven framework for drug‑target interaction prediction that preserves weak biochemical signals by using IterProbe to retain contextual states and BindingProbe to model cross‑entity complementarity at multiple scales. The method improves AUC‑ROC by 2.0% on BindingDB and 0.5% on DrugBank compared to prior biochemical representation learning approaches. Feature‑level analyses confirm the effectiveness of the probe-driven pattern matching, and the predictions are linked to an evidence‑guided downstream drug‑discovery workflow for candidate refinement and validation planning.
ProbeMatchDTI is a new framework for drug‑target interaction prediction that uses probe‑driven pattern matching to preserve weak biochemical signals. It introduces IterProbe, which retains contextual states across refinement depths and selects them with learnable probes, and BindingProbe, which models drug‑protein complementarity at both local and whole‑pair levels. Experiments show that ProbeMatchDTI outperforms existing methods, improving AUC‑ROC by 2.0% on BindingDB and 0.5% on DrugBank, and its predictions can be integrated into downstream drug‑discovery workflows.
The paper refactors and expands the scikit-rebate Python package, adding new Relief‑Based Algorithm (RBA) variants such as SWRF*, mu‑Relief, and five novel methods that use alternative neighbor selection and feature scoring strategies. Benchmarking across diverse genomic simulations shows that most RBAs, except mu‑Relief, effectively detect 2‑way interactions in noisy data, with far‑scoring variants like MultiSWRFDB* excelling at interaction detection but being less sensitive to main effects. The refactored package achieves 10‑ to 35‑fold runtime reductions, and the new RBAs maintain strong performance for both main effects and 2‑way epistatic interactions, preserving predictive signals for downstream modeling.
arXiv:2604. 26498v3 Announce Type: replace Abstract: The rapid growth of molecular foundation models and large language models (LLMs) has encouraged a scale centred view of AI in drug discovery, in which larger pretrained models are expected to supersede compact cheminformatics models.
The study evaluates whether a portfolio of compact, semantically named descriptor blocks can match the performance of a 2048‑dimensional CheMeleon embedding in low‑data molecular assays. Using a fixed 11‑dimensional physicochemical base and greedily adding provenance‑screened blocks, the portfolio achieves a mean test AUC of 0.762 across nine ADME/Tox assays, comparable to CheMeleon’s 0.764 and better than Mordred’s 0.756. The results meet a predeclared pooled parity threshold but not all per‑assay thresholds, and further analysis confirms the competitiveness of the auditable representation while highlighting unresolved assay‑level differences.
arXiv:2606. 03018v1 Announce Type: cross Abstract: Modeling interactions among multimodal, high-dimensional data is intrinsically challenging due to ultra-high dimensionality and complex dependence structure with high level noise.