# Supervised Graph Contrastive Learning for Gene Regulatory Networks

arXiv: https://arxiv.org/abs/2505.17786 · HTML: https://mlsanity.com/paper/2505.17786/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 23 of its 59 references that are in the map.
- First posted on arXiv 23 May 2025.

## Builds on (most cited first, 23 of 23)

- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Optuna: A Next-generation Hyperparameter Optimization Framework](https://mlsanity.com/paper/1907.10902/) (2019)
- [Variational Graph Auto-Encoders](https://mlsanity.com/paper/1611.07308/) (2016)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [Deep Graph Contrastive Representation Learning](https://mlsanity.com/paper/2006.04131/) (2020)
- [Graph Contrastive Learning with Adaptive Augmentation](https://mlsanity.com/paper/2010.14945/) (2020)
- [Masked Label Prediction: Unified Message Passing Model for Semi-Supervised Classification](https://mlsanity.com/paper/2009.03509/) (2020)
- [Understanding the Behaviour of Contrastive Loss](https://mlsanity.com/paper/2012.09740/) (2020)
- [Graph Contrastive Learning Automated](https://mlsanity.com/paper/2106.07594/) (2021)
- [Adversarial Graph Augmentation to Improve Graph Contrastive Learning](https://mlsanity.com/paper/2106.05819/) (2021)
- [Large-Scale Representation Learning on Graphs via Bootstrapping](https://mlsanity.com/paper/2102.06514/) (2021)
- [SimGRACE: A Simple Framework for Graph Contrastive Learning without Data Augmentation](https://mlsanity.com/paper/2202.03104/) (2022)
- [Self-supervised Learning on Graphs: Contrastive, Generative,or Predictive](https://mlsanity.com/paper/2105.07342/) (2021)
- [Augmentation-Free Self-Supervised Learning on Graphs](https://mlsanity.com/paper/2112.02472/) (2021)
- [AutoGCL: Automated Graph Contrastive Learning via Learnable View Generators](https://mlsanity.com/paper/2109.10259/) (2021)
- [ProGCL: Rethinking Hard Negative Mining in Graph Contrastive Learning](https://mlsanity.com/paper/2110.02027/) (2021)
- [A Comprehensive Survey on Deep Graph Representation Learning](https://mlsanity.com/paper/2304.05055/) (2023)
- [I-Con: A Unifying Framework for Representation Learning](https://mlsanity.com/paper/2504.16929/) (2025)
- [MuSe-GNN: Learning Unified Gene Representation From Multimodal Biological Graph Data](https://mlsanity.com/paper/2310.02275/) (2023)
- [Cost Sensitive GNN-based Imbalanced Learning for Mobile Social Network Fraud Detection](https://mlsanity.com/paper/2303.17486/) (2023)
- [On Understanding and Mitigating the Dimensional Collapse of Graph Contrastive Learning: a Non-Maximum Removal Approach](https://mlsanity.com/paper/2203.12821/) (2022)

## Abstract (arXiv)

Graph Contrastive Learning (GCL) is a powerful self-supervised learning framework that performs data augmentation through graph perturbations, with growing applications in the analysis of biological networks such as Gene Regulatory Networks (GRNs). The artificial perturbations commonly used in GCL, such as node dropping, induce structural changes that can diverge from biological reality. This concern has contributed to a broader trend in graph representation learning toward augmentation-free methods, which view such structural changes as problematic and should be avoided. However, this trend overlooks the fundamental insight that structural changes from biologically meaningful perturbations are not a problem to be avoided, but rather a rich source of information, thereby ignoring the valuable opportunity to leverage data from real biological experiments. Motivated by this insight, we propose SupGCL (Supervised Graph Contrastive Learning), a new GCL method for GRNs that directly incorporates biological perturbations from gene knockdown experiments as supervision. SupGCL is a probabilistic formulation that continuously generalizes conventional GCL, linking artificial augmentations with real perturbations measured in knockdown experiments, and using the latter as explicit supervision. On patient-derived GRNs from three cancer types, we train GRN representations with SupGCL and evaluate it in two regimes: (i) embedding space analysis, where it yields clearer disease-subtype structure and improves clustering, and (ii) task-specific fine-tuning, where it consistently outperforms strong graph representation learning baselines on 13 downstream tasks spanning gene-level functional annotation and patient-level prediction.