MolGA: Molecular Graph Adaptation with Pre-trained 2D Graph Encoder

Xingtong Yu, Chang Zhou, Xinming Zhang, Yuan Fang

Main figure for MolGA: Molecular Graph Adaptation with Pre-trained 2D Graph Encoder

Abstract

Molecular graph representation learning is widely used in chemical and biomedical research. While pre-trained 2D graph encoders have demonstrated strong performance, they overlook the rich molecular domain knowledge associated with submolecular instances (atoms and bonds). While molecular pre-training approaches incorporate such knowledge into their pre-training objectives, they typically employ designs tailored to a specific type of knowledge, lacking the flexibility to integrate diverse knowledge present in molecules. Hence, reusing widely available and well-validated pre-trained 2D encoders, while incorporating molecular domain knowledge during downstream adaptation, offers a more practical alternative. In this work, we propose MolGA, which adapts pre-trained 2D graph encoders to downstream molecular applications by flexibly incorporating diverse molecular domain knowledge. First, we propose a molecular alignment strategy that bridge the gap between pre-trained topological representations with domain-knowledge representations. Second, we introduce a conditional adaptation mechanism that generates instance-specific tokens to enable fine-grained integration of molecular domain knowledge for downstream tasks. Finally, we conduct extensive experiments on eleven public datasets, demonstrating the effectiveness of MolGA.

Proposed method: MolGA

Benchmark Results

Tested on 7 datasets 36 baseline values reported too low

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

MoleculeNet

#ModelROC-AUC ↑Paper
1
ProtoMol
0.9140 ±0.0030
2
MMSG
0.9080 ±0.0050
3
MemGNN
0.9070
43
GIN
0.8646 ±0.0081
52
GAT
actual #52 vs paper #320 268 places worse
0.8600 ±0.0110
best reported
actual #52 vs paper #320 268 places worse
paper 0.5021 ±0.0555
paper 0.5021 ±0.0555 Δ at pub 0.3579
62
GEM
actual #62 vs paper #307 245 places worse
0.8560 ±0.0110
best reported
actual #62 vs paper #307 245 places worse
paper 0.5807 ±0.0924
paper 0.5807 ±0.0924 Δ at pub 0.2753 Δ today 0.2753
64
GCN
actual #64 vs paper #319 255 places worse
0.8540 ±0.0110
best reported
actual #64 vs paper #319 255 places worse
paper 0.5053 ±0.0620
paper 0.5053 ±0.0620 Δ at pub 0.3487
96
MoleBlend
actual #96 vs paper #307 211 places worse
0.8370 ±0.0146
best reported
actual #96 vs paper #307 211 places worse
paper 0.5717 ±0.0819
149
GraphMVP
actual #149 vs paper #309 160 places worse
0.8120 ±0.0090
best reported
actual #149 vs paper #309 160 places worse
paper 0.5546 ±0.0610
paper 0.5546 ±0.0610 Δ at pub 0.2574 Δ today 0.2574
213
GraphCL
actual #213 vs paper #316 103 places worse
0.7820 ±0.0120
best reported
actual #213 vs paper #316 103 places worse
paper 0.5220 ±0.0619
paper 0.5220 ±0.0619 Δ at pub 0.2600
290
GraphPrompt
actual #290 vs paper #316 26 places worse
0.6770 ±0.0126
best reported
actual #290 vs paper #316 26 places worse
paper 0.5243 ±0.0362
paper 0.5243 ±0.0362 Δ at pub 0.1527
310
MolGA
0.5494 ±0.0537
This paper
311
ComENet
0.5457 ±0.1021
This paper
312
SphereNet
0.5443 ±0.1341
This paper
313
DimeNet++
0.5406 ±0.1300
This paper
#ModelROC-AUC ↑Paper
1
MAGPrompt+
0.9432 ±0.0238
2
CamS-LLaMA
0.9420
3
SE(3)-I MPPH
0.9400 ±0.0210
34
GIN
0.8875 ±0.0049
36
GraphCL
actual #36 vs paper #275 239 places worse
0.8870 ±0.0190
best reported
actual #36 vs paper #275 239 places worse
paper 0.6461 ±0.1224
paper 0.6461 ±0.1224 Δ at pub 0.2409
38
GCN
actual #38 vs paper #249 211 places worse
0.8810 ±0.0360
best reported
actual #38 vs paper #249 211 places worse
paper 0.6623 ±0.1383
paper 0.6623 ±0.1383 Δ at pub 0.2187
49
GraphMVP
actual #49 vs paper #177 128 places worse
0.8600 ±0.0340
best reported
actual #49 vs paper #177 128 places worse
paper 0.6905 ±0.0800
paper 0.6905 ±0.0800 Δ at pub 0.1695
83
MoleBlend
actual #83 vs paper #116 33 places worse
0.7300 ±0.0081
best reported
actual #83 vs paper #116 33 places worse
paper 0.7145 ±0.0945

Difference within reported uncertainty; not counted as underperformance.

paper 0.7145 ±0.0945 Δ at pub 0.0155 Δ today 0.0155
93
GEM
actual #93 vs paper #107 14 places worse
0.7240 ±0.0040
best reported
actual #93 vs paper #107 14 places worse
paper 0.7178 ±0.0780

Difference within reported uncertainty; not counted as underperformance.

paper 0.7178 ±0.0780 Δ at pub 0.0062 Δ today 0.0062
106
MolGA
0.7197 ±0.1234
This paper
171
GraphPrompt
actual #171 vs paper #183 12 places worse
0.6929 ±0.0019
best reported
actual #171 vs paper #183 12 places worse
paper 0.6888 ±0.1103

Difference within reported uncertainty; not counted as underperformance.

paper 0.6888 ±0.1103 Δ at pub 0.0041
210
GAT
actual #210 vs paper #305 95 places worse
0.6776
best reported
actual #210 vs paper #305 95 places worse
paper 0.5972 ±0.1242

Difference within reported uncertainty; not counted as underperformance.

paper 0.5972 ±0.1242 Δ at pub 0.0804
239
ComENet
0.6689 ±0.0994
This paper
245
DimeNet++
0.6641 ±0.1043
This paper
264
SphereNet
0.6554 ±0.1051
This paper
#ModelROC-AUC ↑Paper
1
SE(3)-I MPPH
0.9930 ±0.0040
2
KA-GCN
0.9920 ±0.0050
3
KA-GAT
0.9910 ±0.0050
19
GCN
actual #19 vs paper #240 221 places worse
0.9130 ±0.0170
best reported
actual #19 vs paper #240 221 places worse
paper 0.5459 ±0.0533
paper 0.5459 ±0.0533 Δ at pub 0.3671
24
GEM
actual #24 vs paper #216 192 places worse
0.9010 ±0.0130
best reported
actual #24 vs paper #216 192 places worse
paper 0.6232 ±0.0731
36
GIN
0.8810 ±0.0250
42
MoleBlend
actual #42 vs paper #219 177 places worse
0.8760 ±0.0075
best reported
actual #42 vs paper #219 177 places worse
paper 0.6056 ±0.0636
49
GraphMVP
actual #49 vs paper #233 184 places worse
0.8650 ±0.0170
best reported
actual #49 vs paper #233 184 places worse
paper 0.5743 ±0.0612
66
GAT
actual #66 vs paper #241 175 places worse
0.8260 ±0.0450
best reported
actual #66 vs paper #241 175 places worse
paper 0.5291 ±0.0457
paper 0.5291 ±0.0457 Δ at pub 0.2969
97
GraphCL
actual #97 vs paper #240 143 places worse
0.7890 ±0.0420
best reported
actual #97 vs paper #240 143 places worse
paper 0.5558 ±0.0684
paper 0.5558 ±0.0684 Δ at pub 0.2332 Δ today 0.2332
121
DimeNet++
actual #121 vs paper #240 119 places worse
0.7600
best reported
actual #121 vs paper #240 119 places worse
paper 0.5425 ±0.1054
paper 0.5425 ±0.1054 Δ at pub 0.2175
234
MolGA
0.5731 ±0.0687
This paper
237
ComENet
0.5589 ±0.0909
This paper
239
GraphPrompt
actual #239 vs paper #239
0.5567 ±0.0708
actual #239 vs paper #239
paper 0.5567 ±0.0708

Improvement within reported uncertainty; not highlighted.

paper 0.5567 ±0.0708 Δ at pub 0.0030
241
SphereNet
0.5383 ±0.1087
This paper
#ModelROC-AUC ↑Paper
1
KA-GAT
0.8470 ±0.0020
2
KA-GCN
0.8420 ±0.0010
3
GraphKAN
0.8370 ±0.0010
18
GEM
actual #18 vs paper #235 217 places worse
0.6720 ±0.0040
best reported
actual #18 vs paper #235 217 places worse
paper 0.5417 ±0.0630
50
MoleBlend
actual #50 vs paper #235 185 places worse
0.6490 ±0.0035
best reported
actual #50 vs paper #235 185 places worse
paper 0.5285 ±0.0425
66
GIN
0.6403 ±0.0104
70
GraphMVP
actual #70 vs paper #238 168 places worse
0.6390 ±0.0120
best reported
actual #70 vs paper #238 168 places worse
paper 0.5082 ±0.0419
114
GraphCL
actual #114 vs paper #237 123 places worse
0.6183 ±0.0060
best reported
actual #114 vs paper #237 123 places worse
paper 0.5159 ±0.0445
125
GCN
actual #125 vs paper #237 112 places worse
0.6150 ±0.0250
best reported
actual #125 vs paper #237 112 places worse
paper 0.5243 ±0.0530
paper 0.5243 ±0.0530 Δ at pub 0.0907
126
DimeNet++
actual #126 vs paper #237 111 places worse
0.6150
best reported
actual #126 vs paper #237 111 places worse
paper 0.5085 ±0.0483
paper 0.5085 ±0.0483 Δ at pub 0.1065
206
GraphPrompt
actual #206 vs paper #237 31 places worse
0.5871 ±0.0013
best reported
actual #206 vs paper #237 31 places worse
paper 0.5153 ±0.0420
paper 0.5153 ±0.0420 Δ at pub 0.0718
236
MolGA
0.5261 ±0.0542
This paper
238
GAT
0.5084 ±0.0550
This paper
239
ComENet
0.5052 ±0.0622
This paper
240
SphereNet
0.5026 ±0.0592
This paper
#ModelRMSE ↓Paper
1
Graphormer-SPIS
0.4840 ±0.0050
2
Graphormer-SPD
0.4920 ±0.0040
3
conan-FGW
0.5140 ±0.0190
5
GAT
actual #5 vs paper #148 143 places worse
0.5520 ±0.0070
best reported
actual #5 vs paper #148 143 places worse
paper 2.6350 ±0.1160
paper 2.6350 ±0.1160 Δ at pub 2.0830
7
GCN
actual #7 vs paper #148 141 places worse
0.5640 ±0.0150
best reported
actual #7 vs paper #148 141 places worse
paper 2.7640 ±0.1220
paper 2.7640 ±0.1220 Δ at pub 2.2000
18
GraphSAGE
0.6010 ±0.0080
26
DimeNet++
actual #26 vs paper #148 122 places worse
0.6330
best reported
actual #26 vs paper #148 122 places worse
paper 2.3770 ±0.0780
paper 2.3770 ±0.0780 Δ at pub 1.7440
79
GraphCL
actual #79 vs paper #142 63 places worse
0.9590 ±0.0470
best reported
actual #79 vs paper #142 63 places worse
paper 2.0380 ±0.0470
paper 2.0380 ±0.0470 Δ at pub 1.0790 Δ today 1.0790
98
GraphMVP
actual #98 vs paper #145 47 places worse
1.0910 ±0.0210
best reported
actual #98 vs paper #145 47 places worse
paper 2.2570 ±0.0430
paper 2.2570 ±0.0430 Δ at pub 1.1660 Δ today 1.1660
111
GEM
1.1750 ±0.0200
This paper
128
MoleBlend
1.4960 ±0.0320
This paper
141
MolGA
1.9730 ±0.0430
This paper
143
GraphPrompt
2.0520 ±0.0450
This paper
144
SphereNet
2.1350 ±0.1510
This paper
147
ComENet
2.3170 ±0.2100
This paper
#ModelRMSE ↓Paper
1
SE(3)-I MPPH
0.3540 ±0.0530
2
ECFP-4 + RF
0.5600 ±0.0660
3
GPSE + GPS
0.6820
10
DimeNet++
actual #10 vs paper #115 105 places worse
0.9780
best reported
actual #10 vs paper #115 105 places worse
paper 4.0490 ±0.2130
paper 4.0490 ±0.2130 Δ at pub 3.0710
39
MoleBlend
1.8510 ±0.0680
This paper
47
GEM
1.9570 ±0.0730
This paper
69
GIN
2.3460 ±0.1220
77
GCN
actual #77 vs paper #118 41 places worse
2.6180 ±0.2980
best reported
actual #77 vs paper #118 41 places worse
paper 4.2980 ±0.1430
paper 4.2980 ±0.1430 Δ at pub 1.6800
86
GraphMVP
2.7670 ±0.0330
This paper
95
GAT
actual #95 vs paper #118 23 places worse
2.9420 ±0.5910
best reported
actual #95 vs paper #118 23 places worse
paper 4.2670 ±0.2030
paper 4.2670 ±0.2030 Δ at pub 1.3250
101
GraphCL
actual #101 vs paper #121 20 places worse
3.1660 ±0.0270
best reported
actual #101 vs paper #121 20 places worse
paper 4.6120 ±0.1330
110
MolGA
3.6020 ±0.1310
This paper
113
SphereNet
3.9000 ±0.1380
This paper
116
ComENet
4.0490 ±0.2850
This paper
120
GraphPrompt
4.5170 ±0.1290
This paper
#ModelRMSE ↓Paper
1
MemGNN
0.5560 ±0.0230
2
ProtoS-L2
0.5800 ±0.0160
3
ProtoW-L2
0.6040 ±0.0140
7
GCN
actual #7 vs paper #103 96 places worse
0.6550 ±0.0360
best reported
actual #7 vs paper #103 96 places worse
paper 1.4660 ±0.1310
best at pub: Memory-Based Graph Networks (ICLR 2020)
paper 1.4660 ±0.1310 Δ at pub 0.8110
9
GIN
0.6580 ±0.0190
24
GraphCL
actual #24 vs paper #98 74 places worse
0.7140 ±0.0110
best reported
actual #24 vs paper #98 74 places worse
paper 1.2490 ±0.0140
27
GraphMVP
actual #27 vs paper #83 56 places worse
0.7180
best reported
actual #27 vs paper #83 56 places worse
paper 0.9450 ±0.0140
paper 0.9450 ±0.0140 Δ at pub 0.2270 Δ today 0.2270
40
DimeNet++
actual #40 vs paper #103 63 places worse
0.7420
best reported
actual #40 vs paper #103 63 places worse
paper 1.3790 ±0.1330
paper 1.3790 ±0.1330 Δ at pub 0.6370
43
GAT
actual #43 vs paper #103 60 places worse
0.7530
best reported
actual #43 vs paper #103 60 places worse
paper 1.4450 ±0.0680
paper 1.4450 ±0.0680 Δ at pub 0.6920
49
MoleBlend
0.7740 ±0.0120
This paper
67
GEM
0.8400 ±0.2200
This paper
97
MolGA
1.1870 ±0.0150
This paper
98
GraphPrompt
1.2420 ±0.0170
This paper
100
ComENet
1.3090 ±0.0480
This paper
101
SphereNet
1.3350 ±0.1270
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 result worse than the best known when published (best reported in green) Best today — OK at publication; today's leaderboard best is elsewhere