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Biomedicine × machine learning · Literature briefNature Biotechnology · April 2026

A survey of 220 biomedical foundation models

Biomedical Foundation Models Are Moving From One Modality to Many

A survey of 220 biomedicine-specific foundation models developed over four years. More than half — 53.6% — already combine two or more data modalities, and natural language is emerging as the connective interface between otherwise unrelated kinds of biomedical data. General-purpose large language models such as ChatGPT, Gemini and Claude were deliberately excluded.

  • 220models curated, over four years
  • 53.6%are multimodal — 118 combine two or more modalities
  • 17distinct data modalities in total
  • 4domains: language, imaging, omics, sequences

What Counts as a Biomedical Foundation Model the survey's boundaries

  • Large-scale machine learning models trained on varied biomedical and clinical data.
  • That data spans genetic sequences, molecular profiling, biomedical imaging and electronic health records.
  • They learn generalisable representations to support downstream discovery and clinical work.
  • The survey covers four domains: natural language, imaging and signals, omics, and molecular sequences.
  • General-purpose LLMs are excluded; the focus is 220 biomedicine-specific models.

The key observation

Natural language is the modality most often paired with others, and is becoming the connective interface between data types. This runs through the whole paper: the emerging citation leaders and the underdeveloped directions both point back to the same structure.

Encoders Dominate architecture breakdown

ArchitectureCountShare
Encoder-based11451.8%
Mixed6730.5%
Decoder-based3114.1%
Non-Transformer (e.g. Mamba)3.6%

Decoders are scarce not out of architectural preference but because of data: text-generation tasks need high-quality paired image–text annotation, and that is hard to obtain in biomedicine.

Evaluation Is Still Narrow downstream tasks used

TaskShare
Classification50.9%
Report generation10.9%
Question answering8.6%
Segmentation7.3%

The evaluation gap

There are no multitask benchmarks, little human-in-the-loop assessment, and no combined treatment of data quality, interpretability and translational relevance. Half of these models have been tested on classification alone.

Citation Leaders by Domain * marks a multimodal model

DomainLeading models and citations
Natural languageBioBERT 6,925 · MultiMedQA 3,707 · PubMedBERT 2,278
Imaging and signalsUNI 1,141 · ConVIRT* 1,003 · MedCLIP* 794
OmicsscGPT 846 · Geneformer 836 · scBERT 509
Molecular sequencesESM-1b 2,807 · ProtTrans 1,207 · DNABERT 1,051

The Risers Since 2025 growth is coming from multimodal work

ModelDomainCitations
BiomedCLIP*Imaging + language498
Quilt-1M*Pathology + language216
ESM3Protein sequences201
Evo-2DNA / RNA197
BorzoiMolecular sequences190
MedGemma-27BNatural language165
Nicheformer*Omics81
OmiCLIP*Imaging + omics58

Citation growth is being driven by models that integrate heterogeneous modalities rather than by specialists in a single data type. Four of the eight risers are multimodal.

The Integrations Nobody Has Built Yet three openings, one shared bottleneck

  • Mechanistic interpretability

    Language ↔ sequence and omics

    • A language interface could assist scRNA-seq annotation, pathway enrichment and spatial transcriptomics.
  • Therapeutic targets

    Imaging ↔ omics

    • Integration of H&E pathology with omics remains weak.
    • The potential to link tissue morphology to molecular mechanism is considerable.
  • Regulatory layers

    DNA, RNA, protein, epigenome

    • The layers are only loosely connected, protein to the others most of all.

The bottleneck is not ideas

What blocks this is not a shortage of concepts but the state of the data: paired datasets are scarce, preprocessing and annotation are not standardised, and there is no standard multimodal benchmark. It is the same cause that explains the scarcity of decoders earlier.

What Gets a Model Adopted and what still stands in the way

  • It addresses a high-impact application: clinical language processing, protein modelling, digital pathology.
  • It is rigorously evaluated: testing across varied downstream tasks builds trust and reuse.
  • It is accessible: open pretrained weights, open code, a usable interface.
  • And newly decisive: it fits into agent-based AI workflows.

Still unsolved

Data quality, cohort diversity, batch effects, privacy, hallucination and adversarial robustness all still limit real-world deployment. The authors recommend cross-disciplinary collaboration — biologists, clinicians and model developers together — and efficient adaptation of strong pretrained backbones in place of training from scratch.