LengthLogD: A Length-Stratified Ensemble Framework for Enhanced Peptide Lipophilicity Prediction via Multi-Scale Feature Integration

Peptide compounds demonstrate considerable potential as therapeutic agents due to their high target affinity and low toxicity, yet their drug development is constrained by their low membrane permeability. Molecular weight and peptide length have significant effects on the logD of peptides, which in turn influences their ability to cross biological membranes. However, accurate prediction of peptide logD remains challenging due to the complex interplay between sequence, structure, and ionization states. This study introduces LengthLogD, a predictive framework that establishes specialized models through molecular length stratification while innovatively integrating multi-scale molecular representations. We constructed feature spaces across three hierarchical levels: atomic (10 molecular descriptors), structural (1024-bit Morgan fingerprints), and topological (3 graph-based features including Wiener index), optimized through stratified ensemble learning. An adaptive weight allocation mechanism specifically developed for long peptides significantly enhances model generalizability. Experimental results demonstrate superior performance across all categories: short peptides (R^2=0.855), medium peptides (R^2=0.816), and long peptides (R^2=0.882), with a 34.7% reduction in prediction error for long peptides compared to conventional single-model approaches. Ablation studies confirm: 1) The length-stratified strategy contributes 41.2% to performance improvement; 2) Topological features account for 28.5% of predictive importance. Compared to state-of-the-art models, our method maintains short peptide prediction accuracy while achieving a 25.7% increase in the coefficient of determination (R^2) for long peptides. This research provides a precise logD prediction tool for peptide drug development, particularly demonstrating unique value in optimizing long peptide lead compounds.

BMMDetect: A Multimodal Deep Learning Framework for Comprehensive Biomedical Misconduct Detection

Academic misconduct detection in biomedical research remains challenging due to algorithmic narrowness in existing methods and fragmented analytical pipelines. We present BMMDetect, a multimodal deep learning framework that integrates journal metadata (SJR, institutional data), semantic embeddings (PubMedBERT), and GPT-4o-mined textual attributes (methodological statistics, data anomalies) for holistic manuscript evaluation. Key innovations include: (1) multimodal fusion of domain-specific features to reduce detection bias; (2) quantitative evaluation of feature importance, identifying journal authority metrics (e.g., SJR-index) and textual anomalies (e.g., statistical outliers) as dominant predictors; and (3) the BioMCD dataset, a large-scale benchmark with 13,160 retracted articles and 53,411 controls. BMMDetect achieves 74.33% AUC, outperforming single-modality baselines by 8.6%, and demonstrates transferability across biomedical subfields. This work advances scalable, interpretable tools for safeguarding research integrity.

Can artificial intelligence predict clinical trial outcomes?

The increasing complexity and cost of clinical trials, particularly in the context of oncology and advanced therapies, pose significant challenges for drug development. This study evaluates the predictive capabilities of large language models (LLMs) such as GPT-3.5, GPT-4, and HINT in determining clinical trial outcomes. By leveraging a curated dataset of trials from ClinicalTrials.gov, we compare the models' performance using metrics including balanced accuracy, specificity, recall, and Matthews Correlation Coefficient (MCC). Results indicate that GPT-4o demonstrates robust performance in early trial phases, achieving high recall but facing limitations in specificity. Conversely, the HINT model excels in recognizing negative outcomes, particularly in later trial phases, offering a balanced approach across diverse endpoints. Oncology trials, characterized by high complexity, remain challenging for all models. Additionally, trial duration and disease categories influence predictive performance, with longer durations and complex diseases such as neoplasms reducing accuracy. This study highlights the complementary strengths of LLMs and HINT, providing insights into optimizing predictive tools for clinical trial design and risk management. Future advancements in LLMs are essential to address current gaps in handling negative outcomes and complex domains.

A deep graph model for the signed interaction prediction in biological network

In pharmaceutical research, the strategy of drug repurposing accelerates the development of new therapies while reducing R&D costs. Network pharmacology lays the theoretical groundwork for identifying new drug indications, and deep graph models have become essential for their precision in mapping complex biological networks. Our study introduces an advanced graph model that utilizes graph convolutional networks and tensor decomposition to effectively predict signed chemical-gene interactions. This model demonstrates superior predictive performance, especially in handling the polar relations in biological networks. Our research opens new avenues for drug discovery and repurposing, especially in understanding the mechanism of actions of drugs.