ES-Merging: Biological MLLM Merging via Embedding Space Signals
Organizations: KAIST
Abstract
Biological multimodal large language models (MLLMs) have emerged as powerful foundation models for scientific discovery. However, existing models are specialized to a single modality, limiting their ability to solve inherently cross-modal scientific problems. While model merging is an efficient method to combine the different modalities into a unified MLLM, existing methods rely on input-agnostic parameter space heuristics that fail to faithfully capture modality specialization. To overcome this limitation, we propose the Embedding-Signal-based MLLM Merging (ES-Merging), a framework that estimates merging coefficients from embedding space signals, moving the merging paradigm from the parameter signals to the embedding signals. ES-Merging exploits coarse-grained and fine-grained signals from embedding space to estimate the layer-wise and element-wise merging coefficients, respectively, which are jointly combined for complementary coefficient estimation. Through extensive experiments, we demonstrate that ES-Merging outperforms existing merging methods not only on the cross-modal reasoning but also on the single-modal knowledge preservation, establishing that embedding space signals provide a principled and effective foundation for MLLM merging.
Figures & tables
| Molecule-Protein Interaction | Molecule-Cell Interaction | |||||||||||||
| BindingDB | BioSNAP | Human | Avg. | DrugComb | GDSC2 | Avg. | ||||||||
| Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | |
| Base LLM and Specialized MLLMs | ||||||||||||||
| LLaMA-3.1-8B-Instruct | 51.9 | 51.7 | 61.5 | 60.2 | 59.0 | 58.8 | 57.5 | 56.9 | 73.7 | 73.6 | 84.8 | 84.7 | 79.3 | 79.1 |
| Mol-LLaMA [ 29 ] | 55.8 | 54.7 | 66.4 | 64.0 | 61.5 | 61.4 | 61.2 | 60.0 | 64.1 | 64.1 | 55.5 | 55.5 | 59.8 | 59.8 |
| Prot2Text-V2 [ 17 ] | 59.2 | 59.2 | 55.3 | 54.1 | 47.2 | 47.2 | 53.9 | 53.5 | 65.6 | 65.6 | 59.7 | 57.9 | 62.6 | 61.7 |
| CYP Inhibition | CYP Substrate | |||||||||||||||||||
| CYP1A2 | CYP2C19 | CYP2C9 | CYP2D6 | CYP3A4 | Avg. | CYP2C9 | CYP2D6 | CYP3A4 | Avg. | |||||||||||
| Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | Acc. | F1 | |
| Base LLM and Specialized MLLMs | ||||||||||||||||||||
| LLaMA-3.1-8B-Instruct | 58.9 | 55.3 | 56.0 | 50.6 | 55.9 | 47.4 | 61.2 | 56.4 | 55.1 | 43.1 | 57.4 | 50.6 | 57.7 | 47.8 | 34.2 | 30.1 | 55.6 | 48.5 | 49.2 | 42.1 |
| Mol-LLaMA | 68.6 | 67.1 | 65.8 | 64.3 | 63.3 | 63.3 | 64.7 | 59.2 | 64.3 | 64.0 | 65.3 | 63.6 | 62.7 | 49.7 | 61.7 | 57.4 | 55.2 | 53.7 | 59.9 | 53.6 |
| Prot2Text-V2 | 59.4 | 55.8 | 56.8 | 52.5 | 67.4 | 60.1 | 76.3 | 55.9 | 59.6 | 50.3 | 63.9 | 54.9 | 54.5 | 47.5 | 53.4 | 51.4 | 56.0 | 53.8 | 54.6 | 50.9 |
Appendix figures & tables13 assets
Supplementary material from the paper’s appendix.
Appendix
| Molecule Name: Paramethasone |
| SMILES: C[C@@H]1C[C@H]2[C@@H]3CC@@HF |
| Protein: Glucocorticoid receptor |
| Protein Sequence: MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRRLLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLKLLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGNVKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGNSNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTVYCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVGSENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKLCLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRKCLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIEPEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSWMFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSYEEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTKLLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK |
| User: Determine whether the given molecule interacts with the protein by following the example. |
| Ground Truth: Interacts |
| Drug Name: Gefitinib |
| SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4 |
| Cell Line: OVCA420 |
| Top 50 Genes: RPL35, FTL, MT-ND4, GAPDH, AKR1B10, UBC, RPS6, RPL24, EIF1, GNB2L1, SPP1, RPS11, AKR1C1, RPL19, GNG5, AKR1B10P1, ACTG1, MT-CO3, RPL5, FAU, RPS15A, TXN, RPL8, MIF, LDHB, KRT19, EIF4H, RPL11, ALDH1A1, MGST1, RPS12, CLIC1, SNRPD2, RPL30, H2AFX, NQO1, PRDX1, RPS5, RPLP1, H2AFZ, TUBB4B, FAUP1, NACA, RPL14, HIST1H2BK, MYL12B, SHFM1P1, HINT1P1, RPL27, HIST1H4C |
| User: Determine whether the given cell is sensitive or resistant to the given molecule based on the ranked gene-expression list. |
| Ground Truth: Sensitive |
| Size | Human | GDSC2 | CYP2C9 Inh. | CYP2C9 Sub. |
|---|---|---|---|---|
| 32 | 60.7 | 90.6 | 68.2 | 53.7 |
| 256 | 62.0 | 93.1 | 68.9 | 48.5 |
| 1024 | 62.0 | 94.1 | 72.5 | 64.2 |
| Molecule | Protein | Cell | |
|---|---|---|---|
| Mol-LLaMA [ 29 ] | 75.68 | 88.02 | 0.00 |
| Prot2Text-V2 [ 17 ] | 39.80 | 85.25 | 0.00 |
| Cell-o1 [ 15 ] | 60.89 | 77.81 | 77.84 |
| Molecule-Protein Interaction | Molecule-Cell Interaction | CYP Inhibition | CYP Substrate | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Coefficient Type | BindingDB | BioSNAP | Human | Avg. | DrugComb | GDSC2 | Avg. | CYP1A2 | CYP2C19 | CYP2C9 | CYP2D6 | CYP3A4 | Avg. | CYP2C9 | CYP2D6 | CYP3A4 | Avg. |
| Layer-wise | 65.5 | 68.2 | 57.0 | 63.6 | 80.1 | 90.2 | 85.2 | 76.3 | 71.4 | 72.3 | 79.2 | 70.2 | 73.9 | 61.2 | 54.9 | 55.2 | 57.1 |
| Element-wise | 66.5 | 66.6 | 61.4 | 64.9 | 79.3 | 94.1 | 86.7 | 76.0 | 69.1 | 70.7 | 77.6 | 69.8 | 72.7 | 65.7 | 57.6 | 58.2 | 60.5 |
| Layer Element Mixed | 66.0 | 69.1 | 62.0 | 65.7 | 80.7 | 94.1 | 87.4 | 77.4 | 70.6 | 72.5 | 80.7 | 71.3 | 74.5 | 64.2 | 60.9 | 60.5 | 61.9 |
| Size | Human | GDSC2 | CYP2D6 Inh. | CYP2D6 Sub. |
|---|---|---|---|---|
| 50 | 61.0 | 91.2 | 78.7 | 59.4 |
| 600 | 61.2 | 92.4 | 79.1 | 60.9 |
| 330 (Another subset) | 61.8 | 93.9 | 79.6 | 60.5 |
| 330 | 62.0 | 94.1 | 80.7 | 60.9 |
Language Model Merging
Language model merging combines capabilities from multiple models or adapters by composing their weights, updates, or outputs.
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