BiScale-GTR: Fragment-Aware Graph Transformers for Multi-Scale Molecular Representation Learning

Yi Yang, O. Daescu

Main figure for BiScale-GTR: Fragment-Aware Graph Transformers for Multi-Scale Molecular Representation Learning

Abstract

Graph Transformers have recently attracted attention for molecular property prediction by combining the inductive biases of graph neural networks (GNNs) with the global receptive field of Transformers. However, many existing hybrid architectures remain GNN-dominated, causing the resulting representations to remain heavily shaped by local message passing. Moreover, most existing methods operate at only a single structural granularity, limiting their ability to capture molecular patterns that span multiple molecular scales. We introduce BiScale-GTR, a unified framework for self-supervised molecular representation learning that combines chemically grounded fragment tokenization with adaptive multi-scale reasoning. Our method improves graph Byte Pair Encoding (BPE) tokenization to produce consistent, chemically valid, and high-coverage fragment tokens, which are used as fragment-level inputs to a parallel GNN-Transformer architecture. Architecturally, atom-level representations learned by a GNN are pooled into fragment-level embeddings and fused with fragment token embeddings before Transformer reasoning, enabling the model to jointly capture local chemical environments, substructure-level motifs, and long-range molecular dependencies. Experiments on MoleculeNet, PharmaBench, and the Long Range Graph Benchmark (LRGB) demonstrate state-of-the-art performance across both classification and regression tasks. Attribution analysis further shows that BiScale-GTR highlights chemically meaningful functional motifs, providing interpretable links between molecular structure and predicted properties. Code will be released upon acceptance.

Proposed method: BiScale-GTR (Molecule)

Benchmark Results

Tested on 1 dataset

Tables show presented results in global context (best 3 papers + GCN + MLP).

MoleculeNet

#ModelRMSE ↓Paper
1
Graphormer-SPIS
0.4840 ±0.0050
2
Graphormer-SPD
0.4920 ±0.0040
3
conan-FGW
0.5140 ±0.0190
7
GCN
0.5640 ±0.0150
37
UniMol
actual #37 vs paper #37
0.7070
actual #37 vs paper #37
paper 0.7070
paper 0.7070 Δ at pub 0.0810
39
FPGNN
0.7470
This paper
40
MPG
0.7580
This paper
42
KANO
0.7720
This paper
52
DHTNN
0.8280
This paper
54
XGBoost
actual #54 vs paper #54
0.8320
actual #54 vs paper #54
paper 0.8320
prev best: MoleculeNet (2017)

Improvement within reported uncertainty; not highlighted.

paper 0.8320 Δ at pub 0.1580
57
Trans-M
0.8340
This paper
62
CMPNN
0.8580
This paper
67
FragFormer
0.8950
This paper
70
rf
actual #70 vs paper #70
0.9180
actual #70 vs paper #70
paper 0.9180
prev best: MoleculeNet (2017)

Improvement within reported uncertainty; not highlighted.

paper 0.9180 Δ at pub 0.1520
78
PharmHGT
0.9540
This paper
81
BiScale-GTR (Molecule)
0.9770
This paper
118
KP-GPT
1.2210
This paper
122
FraGAT
1.3520
This paper
140
GraphFP
actual #140 vs paper #140
1.9350
actual #140 vs paper #140
paper 1.9350
SOTA performance (not significantly different from the best) Proposed method (this paper) Baseline / comparison (this paper) Global context (other papers) Best at pub — reported value improved over the best known when published