# PhenoGnet: A Graph-Based Contrastive Learning Framework for Disease Similarity Prediction

arXiv: https://arxiv.org/abs/2509.14037 · HTML: https://mlsanity.com/paper/2509.14037/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 6 of its 27 references that are in the map.
- First posted on arXiv 17 Sep 2025.

## Builds on (most cited first, 6 of 6)

- [Sentence-BERT: Sentence Embeddings using Siamese BERT-Networks](https://mlsanity.com/paper/1908.10084/) (2019)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Optuna: A Next-generation Hyperparameter Optimization Framework](https://mlsanity.com/paper/1907.10902/) (2019)
- [MPNet: Masked and Permuted Pre-training for Language Understanding](https://mlsanity.com/paper/2004.09297/) (2020)
- [Contrastive Multi-View Representation Learning on Graphs](https://mlsanity.com/paper/2006.05582/) (2020)
- [Multi-task Joint Strategies of Self-supervised Representation Learning on Biomedical Networks for Drug Discovery](https://mlsanity.com/paper/2201.04437/) (2022)

## Abstract (arXiv)

Understanding disease similarity is critical for advancing diagnostics, drug discovery, and personalized treatment strategies. We present PhenoGnet, a novel graph-based contrastive learning framework designed to predict disease similarity by integrating gene functional interaction networks with the Human Phenotype Ontology (HPO). PhenoGnet comprises two key components: an intra-view model that separately encodes gene and phenotype graphs using Graph Convolutional Networks (GCNs) and Graph Attention Networks (GATs), and a cross view model implemented as a shared weight multilayer perceptron (MLP) that aligns gene and phenotype embeddings through contrastive learning. The model is trained using known gene phenotype associations as positive pairs and randomly sampled unrelated pairs as negatives. Diseases are represented by the mean embeddings of their associated genes and/or phenotypes, and pairwise similarity is computed via cosine similarity. Evaluation on a curated benchmark of 1,100 similar and 866 dissimilar disease pairs demonstrates strong performance, with gene based embeddings achieving an AUCPR of 0.9012 and AUROC of 0.8764, outperforming existing state of the art methods. Notably, PhenoGnet captures latent biological relationships beyond direct overlap, offering a scalable and interpretable solution for disease similarity prediction. These results underscore its potential for enabling downstream applications in rare disease research and precision medicine.