# Active learning for efficient discovery of optimal gene combinations in the combinatorial perturbation space

arXiv: https://arxiv.org/abs/2411.12010 · HTML: https://mlsanity.com/paper/2411.12010/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 9 of its 35 references that are in the map.
- First posted on arXiv 18 Nov 2024.

## Builds on (most cited first, 9 of 9)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [A Tutorial on Bayesian Optimization](https://mlsanity.com/paper/1807.02811/) (2018)
- [DEUP: Direct Epistemic Uncertainty Prediction](https://mlsanity.com/paper/2102.08501/) (2021)
- [Modelling Cellular Perturbations with the Sparse Additive Mechanism Shift Variational Autoencoder](https://mlsanity.com/paper/2311.02794/) (2023)
- [Learning Causal Representations of Single Cells via Sparse Mechanism Shift Modeling](https://mlsanity.com/paper/2211.03553/) (2022)
- [On Initial Pools for Deep Active Learning](https://mlsanity.com/paper/2011.14696/) (2020)
- [Season combinatorial intervention predictions with Salt & Peper](https://mlsanity.com/paper/2404.16907/) (2024)

## Built on by (most cited first, 1 of 1)

- [LLM-AutoSciLab: Closed-Loop Scientific Discovery via Active Experimentation with LLMs](https://mlsanity.com/paper/2605.24043/) (2026)

## Abstract (arXiv)

The advancement of novel combinatorial CRISPR screening technologies enables the identification of synergistic gene combinations on a large scale. This is crucial for developing novel and effective combination therapies, but the combinatorial space makes exhaustive experimentation infeasible. We introduce NAIAD, an active learning framework that efficiently discovers optimal gene pairs capable of driving cells toward desired cellular phenotypes. NAIAD leverages single-gene perturbation effects and adaptive gene embeddings that scale with the training data size, mitigating overfitting in small-sample learning while capturing complex gene interactions as more data is collected. Evaluated on four CRISPR combinatorial perturbation datasets totaling over 350,000 genetic interactions, NAIAD, trained on small datasets, outperforms existing models by up to 40% relative to the second-best. NAIAD's recommendation system prioritizes gene pairs with the maximum predicted effects, resulting in the highest marginal gain in each AI-experiment round and accelerating discovery with fewer CRISPR experimental iterations. Our NAIAD framework (https://github.com/NeptuneBio/NAIAD) improves the identification of novel, effective gene combinations, enabling more efficient CRISPR library design and offering promising applications in genomics research and therapeutic development.