Wojciech Czech

Jakub Adamczyk, Wojciech Czech

We revisit the effectiveness of topological descriptors for molecular graph classification and design a simple, yet strong baseline. We demonstrate that a simple approach to feature engineering - employing histogram aggregation of edge descriptors and one-hot encoding for atomic numbers and bond types - when combined with a Random Forest classifier, can establish a strong baseline for Graph Neural Networks (GNNs). The novel algorithm, Molecular Topological Profile (MOLTOP), integrates Edge Betweenness Centrality, Adjusted Rand Index and SCAN Structural Similarity score. This approach proves to be remarkably competitive when compared to modern GNNs, while also being simple, fast, low-variance and hyperparameter-free. Our approach is rigorously tested on MoleculeNet datasets using fair evaluation protocol provided by Open Graph Benchmark. We additionally show out-of-domain generation capabilities on peptide classification task from Long Range Graph Benchmark. The evaluations across eleven benchmark datasets reveal MOLTOP's strong discriminative capabilities, surpassing the $1$-WL test and even $3$-WL test for some classes of graphs. Our conclusion is that descriptor-based baselines, such as the one we propose, are still crucial for accurately assessing advancements in the GNN domain.

Jakub Adamczyk, Wojciech Czech

We present the analysis of the topological graph descriptor Local Degree Profile (LDP), which forms a widely used structural baseline for graph classification. Our study focuses on model evaluation in the context of the recently developed fair evaluation framework, which defines rigorous routines for model selection and evaluation for graph classification, ensuring reproducibility and comparability of the results. Based on the obtained insights, we propose a new baseline algorithm called Local Topological Profile (LTP), which extends LDP by using additional centrality measures and local vertex descriptors. The new approach provides the results outperforming or very close to the latest GNNs for all datasets used. Specifically, state-of-the-art results were obtained for 4 out of 9 benchmark datasets. We also consider computational aspects of LDP-based feature extraction and model construction to propose practical improvements affecting execution speed and scalability. This allows for handling modern, large datasets and extends the portfolio of benchmarks used in graph representation learning. As the outcome of our work, we obtained LTP as a simple to understand, fast and scalable, still robust baseline, capable of outcompeting modern graph classification models such as Graph Isomorphism Network (GIN). We provide open-source implementation at \href{https://github.com/j-adamczyk/LTP}{GitHub}.

Mateusz Praski, Jakub Adamczyk, Wojciech Czech

Pretrained neural networks have attracted significant interest in chemistry and small molecule drug design. Embeddings from these models are widely used for molecular property prediction, virtual screening, and small data learning in molecular chemistry. This study presents the most extensive comparison of such models to date, evaluating 25 models across 25 datasets. Under a fair comparison framework, we assess models spanning various modalities, architectures, and pretraining strategies. Using a dedicated hierarchical Bayesian statistical testing model, we arrive at a surprising result: nearly all neural models show negligible or no improvement over the baseline ECFP molecular fingerprint. Only the CLAMP model, which is also based on molecular fingerprints, performs statistically significantly better than the alternatives. These findings raise concerns about the evaluation rigor in existing studies. We discuss potential causes, propose solutions, and offer practical recommendations.

Jakub Adamczyk, Piotr Ludynia, Wojciech Czech

Understanding peptide properties is often assumed to require modeling long-range molecular interactions, motivating the use of complex graph neural networks and pretrained transformers. Yet, whether such long-range dependencies are essential remains unclear. We investigate if simple, domain-specific molecular fingerprints can capture peptide function without these assumptions. Atomic-level representation aims to provide richer information than purely sequence-based models and better efficiency than structural ones. Across 132 datasets, including LRGB and five other peptide benchmarks, models using count-based ECFP, Topological Torsion, and RDKit fingerprints with LightGBM achieve state-of-the-art accuracy. Despite encoding only short-range molecular features, these models outperform GNNs and transformer-based approaches. Control experiments with sequence shuffling and amino acid counts confirm that fingerprints, though inherently local, suffice for robust peptide property prediction. Our results challenge the presumed necessity of long-range interaction modeling and highlight molecular fingerprints as efficient, interpretable, and computationally lightweight alternatives for peptide prediction.