KDD 2022

KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction

Han Li, Dan Zhao, Jianyang Zeng

Main figure for KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction

Abstract

Designing accurate deep learning models for molecular property prediction plays an increasingly essential role in drug and material discovery. Recently, due to the scarcity of labeled molecules, self-supervised learning methods for learning generalizable and transferable representations of molecular graphs have attracted lots of attention. In this paper, we argue that there exist two major issues hindering current self-supervised learning methods from obtaining desired performance on molecular property prediction, that is, the ill-defined pre-training tasks and the limited model capacity. To this end, we introduce Knowledge-guided Pre-training of Graph Transformer (KPGT), a novel self-supervised learning framework for molecular graph representation learning, to alleviate the aforementioned issues and improve the performance on the downstream molecular property prediction tasks. More specifically, we first introduce a high-capacity model, named Line Graph Transformer (LiGhT), which emphasizes the importance of chemical bonds and is mainly designed to model the structural information of molecular graphs. Then, a knowledge-guided pre-training strategy is proposed to exploit the additional knowledge of molecules to guide the model to capture the abundant structural and semantic information from large-scale unlabeled molecular graphs. Extensive computational tests demonstrated that KPGT can offer superior performance over current state-of-the-art methods on several molecular property prediction tasks.

Proposed method: KPGT

Benchmark Results

Tested on 5 datasets

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

MoleculeNet

#ModelROC-AUC ↑Paper
1
HIMP
0.8740 ±0.0050
2
GINE w/ VN
0.8720 ±0.0030
3
NaiveGINe+ K=3 w/ VN
0.8700 ±0.0040
9
KPGT
0.8480 ±0.0130
This paper
13
Contextpred+Sup
0.8400 ±0.0230
This paper
14
GCN
0.8400 ±0.0040
15
GROVER
actual #15 vs paper #15
0.8380 ±0.0170
actual #15 vs paper #15
paper 0.8380 ±0.0170
paper 0.8380 ±0.0170 Δ at pub 0.0750
25
Masking+Sup
0.8280 ±0.0130
This paper
31
JOAO
actual #31 vs paper #31
0.8230 ±0.0220
actual #31 vs paper #31
paper 0.8230 ±0.0220
paper 0.8230 ±0.0220 Δ at pub 0.0730
35
EdgePred
actual #35 vs paper #35
0.8180 ±0.0250
actual #35 vs paper #35
paper 0.8180 ±0.0250
paper 0.8180 ±0.0250 Δ at pub 0.0730
37
Infomax
actual #37 vs paper #37
0.8160 ±0.0210
actual #37 vs paper #37
paper 0.8160 ±0.0210
paper 0.8160 ±0.0210 Δ at pub 0.0640
46
ContextPred
actual #46 vs paper #46
0.8060 ±0.0120
actual #46 vs paper #46
paper 0.8060 ±0.0120
paper 0.8060 ±0.0120 Δ at pub 0.0730
47
GraphCL
actual #47 vs paper #47
0.8050 ±0.0170
actual #47 vs paper #47
paper 0.8050 ±0.0170
paper 0.8050 ±0.0170 Δ at pub 0.0510
48
3D Infomax
0.8050 ±0.0320
This paper
61
GraphMVP
actual #61 vs paper #61
0.7990 ±0.0180
actual #61 vs paper #61
paper 0.7990 ±0.0180
paper 0.7990 ±0.0180 Δ at pub 0.0540
66
masking
0.7980 ±0.0250
This paper
71
GraphLoG
actual #71 vs paper #71
0.7960 ±0.0250
actual #71 vs paper #71
paper 0.7960 ±0.0250
paper 0.7960 ±0.0250 Δ at pub 0.0660
#ModelROC-AUC ↑Paper
1
ProtoMol
0.9140 ±0.0030
2
MMSG
0.9080 ±0.0050
3
MemGNN
0.9070
36
KPGT
0.8680 ±0.0110
This paper
43
GIN
0.8646 ±0.0081
100
JOAO
actual #100 vs paper #100
0.8340 ±0.0330
actual #100 vs paper #100
paper 0.8340 ±0.0330
paper 0.8340 ±0.0330 Δ at pub 0.0610
#ModelROC-AUC ↑Paper
1
MAGPrompt+
0.9432 ±0.0238
2
CamS-LLaMA
0.9420
3
SE(3)-I MPPH
0.9400 ±0.0210
32
KPGT
0.9080 ±0.0100
This paper
34
GIN
0.8875 ±0.0049
36
GraphCL
actual #36 vs paper #36
0.8870 ±0.0190
actual #36 vs paper #36
paper 0.8870 ±0.0190
paper 0.8870 ±0.0190 Δ at pub 0.1900
37
GROVER
actual #37 vs paper #37
0.8870 ±0.0060
actual #37 vs paper #37
paper 0.8870 ±0.0060
paper 0.8870 ±0.0060 Δ at pub 0.2070
39
JOAO
actual #39 vs paper #39
0.8790 ±0.0200
actual #39 vs paper #39
paper 0.8790 ±0.0200
paper 0.8790 ±0.0200 Δ at pub 0.1650
40
ContextPred
actual #40 vs paper #40
0.8770 ±0.0260
actual #40 vs paper #40
paper 0.8770 ±0.0260
paper 0.8770 ±0.0260 Δ at pub 0.1650
41
3D Infomax
0.8770 ±0.0140
This paper
43
Contextpred+Sup
0.8750 ±0.0110
This paper
44
EdgePred
actual #44 vs paper #44
0.8730 ±0.0160
actual #44 vs paper #44
paper 0.8730 ±0.0160
paper 0.8730 ±0.0160 Δ at pub 0.2280
47
masking
0.8640 ±0.0280
This paper
49
GraphMVP
actual #49 vs paper #49
0.8600 ±0.0340
actual #49 vs paper #49
paper 0.8600 ±0.0340
paper 0.8600 ±0.0340 Δ at pub 0.1750
50
Masking+Sup
0.8590 ±0.0200
This paper
54
GraphLoG
actual #54 vs paper #54
0.8460 ±0.0080
actual #54 vs paper #54
paper 0.8460 ±0.0080
paper 0.8460 ±0.0080 Δ at pub 0.1680
55
Infomax
actual #55 vs paper #55
0.8400 ±0.0260
actual #55 vs paper #55
paper 0.8400 ±0.0260
paper 0.8400 ±0.0260 Δ at pub 0.1590
#ModelROC-AUC ↑Paper
1
KA-GAT
0.8470 ±0.0020
2
KA-GCN
0.8420 ±0.0010
3
GraphKAN
0.8370 ±0.0010
49
KPGT
0.6490 ±0.0090
This paper
52
GROVER
actual #52 vs paper #72 20 places worse
0.6380 ±0.0050
actual #52 vs paper #72 20 places worse
paper 0.6380 ±0.0050
66
GIN
0.6403 ±0.0104
68
JOAO
actual #68 vs paper #68
0.6400 ±0.0100
actual #68 vs paper #68
paper 0.6400 ±0.0100
paper 0.6400 ±0.0100 Δ at pub 0.0330
70
GraphMVP
actual #70 vs paper #206 136 places worse
0.6390 ±0.0120
best reported
actual #70 vs paper #206 136 places worse
paper 0.5840 ±0.0260
103
ContextPred
actual #103 vs paper #144 41 places worse
0.6090 ±0.0130
actual #103 vs paper #144 41 places worse
paper 0.6090 ±0.0130

Improvement within reported uncertainty; not highlighted.

paper 0.6090 ±0.0130 Δ at pub 0.0160
108
Contextpred+Sup
0.6200 ±0.0090
This paper
114
GraphCL
actual #114 vs paper #206 92 places worse
0.6183 ±0.0060
best reported
actual #114 vs paper #206 92 places worse
paper 0.5870 ±0.0260

Difference within reported uncertainty; not counted as underperformance.

paper 0.5870 ±0.0260 Δ at pub 0.0210 Δ today 0.0313
120
Infomax
actual #120 vs paper #120
0.6160 ±0.0240
actual #120 vs paper #120
paper 0.6160 ±0.0240

Improvement within reported uncertainty; not highlighted.

paper 0.6160 ±0.0240 Δ at pub 0.0340
123
GraphLoG
actual #123 vs paper #123
0.6150 ±0.0130
actual #123 vs paper #123
paper 0.6150 ±0.0130

Improvement within reported uncertainty; not highlighted.

paper 0.6150 ±0.0130 Δ at pub 0.0410
138
Masking+Sup
0.6110 ±0.0030
This paper
155
3D Infomax
actual #155 vs paper #206 51 places worse
0.6060 ±0.0078
best reported
actual #155 vs paper #206 51 places worse
paper 0.5850 ±0.0210

Difference within reported uncertainty; not counted as underperformance.

paper 0.5850 ±0.0210 Δ today 0.0210
170
EdgePred
actual #170 vs paper #174 4 places worse
0.6030 ±0.0250
actual #170 vs paper #174 4 places worse
paper 0.6030 ±0.0250

Improvement within reported uncertainty; not highlighted.

paper 0.6030 ±0.0250 Δ at pub 0.0360
221
masking
actual #221 vs paper #221
0.5730 ±0.0120
actual #221 vs paper #221
paper 0.5730 ±0.0120

Improvement within reported uncertainty; not highlighted.

paper 0.5730 ±0.0120 Δ at pub 0.0070
#ModelROC-AUC ↑Paper
1
GeomGCL
0.7630
2
LiGhT DeepGPT
0.7570 ±0.0110
3
CoMPT
0.7550
6
KPGT
0.7460 ±0.0020
This paper
14
GCN
0.7350 ±0.0020
18
Contextpred+Sup
0.7240 ±0.0150
This paper
25
3D Infomax
0.7160 ±0.0130
This paper
26
Masking+Sup
0.7150 ±0.0070
This paper
28
ContextPred
actual #28 vs paper #28
0.7140 ±0.0180
actual #28 vs paper #28
paper 0.7140 ±0.0180
paper 0.7140 ±0.0180 Δ at pub 0.0860
30
EdgePred
actual #30 vs paper #30
0.7120 ±0.0110
actual #30 vs paper #30
paper 0.7120 ±0.0110
paper 0.7120 ±0.0110 Δ at pub 0.1040
31
JOAO
actual #31 vs paper #31
0.7110 ±0.0140
actual #31 vs paper #31
paper 0.7110 ±0.0140
paper 0.7110 ±0.0140 Δ at pub 0.0790
34
GROVER
actual #34 vs paper #34
0.7080 ±0.0150
actual #34 vs paper #34
paper 0.7080 ±0.0150
paper 0.7080 ±0.0150 Δ at pub 0.0740
42
GraphCL
actual #42 vs paper #42
0.6960 ±0.0230
actual #42 vs paper #42
paper 0.6960 ±0.0230
paper 0.6960 ±0.0230 Δ at pub 0.0580
49
Infomax
actual #49 vs paper #49
0.6900 ±0.0120
actual #49 vs paper #49
paper 0.6900 ±0.0120
paper 0.6900 ±0.0120 Δ at pub 0.0620
50
GraphMVP
actual #50 vs paper #50
0.6890 ±0.0100
actual #50 vs paper #50
paper 0.6890 ±0.0100
paper 0.6890 ±0.0100 Δ at pub 0.0620
64
GraphLoG
actual #64 vs paper #64
0.6770 ±0.0190
actual #64 vs paper #64
paper 0.6770 ±0.0190
paper 0.6770 ±0.0190 Δ at pub 0.0550
83
masking
0.6630 ±0.0180
This paper
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 Improved at pub — later paper surpassed this result Best today — OK at publication; today's leaderboard best is elsewhere