Lucas Arnoldt

NetworkVI is a group effort by @juliusuzb.bsky.social, Luis Herrmann, Khue Nguyen, supervised by @fabiantheis.bsky.social & Benjamin Wild & Roland Eils at @bihatcharite.bsky.social and @www.helmholtz-munich.de‬.
Code: github.com/LArnoldt/networkVI
🧠 Open-source & ready to use!

We demonstrate how NetworkVI identifies immune evasion mechanisms via GO programs in a CRISPR-perturbed melanoma dataset not detectable with standard methods. This highlights the medical utility of interpretable multimodal models.

NetworkVI also incorporates a GO-specific covariate attention mechanism, allowing the model to adjust for sample-level metadata (e.g., donor or condition), improving both performance and interpretability in heterogeneous datasets.

These scores reveal associations between genes and GO terms, helping to identify active biological processes and their regulatory drivers in a given condition or perturbation.
This opens a path toward mechanistic interpretation beyond enrichment tests.

NetworkVI’s architecture incorporates prior biological knowledge:

1. Gene-gene interactions from TADs
2. The structure of the Gene Ontology
This enables inference of gene and GO term importance scores at modality- and cell-specific resolution.

📊 NetworkVI achieves state-of-the-art performance on bimodal and trimodal data:
✅ Accurate integration
✅ Imputation of missing modalities
✅ Query-to-reference mapping
✅ Interpretation of cell type– and perturbation-specific signatures

Current multimodal single-cell integration methods act as black boxes, lacking meaningful interpretability. We introduce NetworkVI, a VAE that performs integration via gene-gene interactions and the Gene Ontology for biologically grounded analysis. www.biorxiv.org/content/10.1...