# Conditionally Invariant Representation Learning for Disentangling Cellular Heterogeneity

arXiv: https://arxiv.org/abs/2307.00558 · HTML: https://mlsanity.com/paper/2307.00558/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 50 of its 87 references that are in the map.
- First posted on arXiv 2 Jul 2023.

## Builds on (most cited first, 30 of 50)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [Invariant Risk Minimization](https://mlsanity.com/paper/1907.02893/) (2019)
- [Challenging Common Assumptions in the Unsupervised Learning of Disentangled Representations](https://mlsanity.com/paper/1811.12359/) (2018)
- [InfoGAN: Interpretable Representation Learning by Information Maximizing Generative Adversarial Nets](https://mlsanity.com/paper/1606.03657/) (2016)
- [Causal inference using invariant prediction: identification and confidence intervals](https://mlsanity.com/paper/1501.01332/) (2015)
- [Variational Autoencoders and Nonlinear ICA: A Unifying Framework](https://mlsanity.com/paper/1907.04809/) (2019)
- [Semi-Supervised Learning with Deep Generative Models](https://mlsanity.com/paper/1406.5298/) (2014)
- [Adversarial Autoencoders](https://mlsanity.com/paper/1511.05644/) (2015)
- [Self-Supervised Learning with Data Augmentations Provably Isolates Content from Style](https://mlsanity.com/paper/2106.04619/) (2021)
- [Nonlinear ICA Using Auxiliary Variables and Generalized Contrastive Learning](https://mlsanity.com/paper/1805.08651/) (2018)
- [Unsupervised Feature Extraction by Time-Contrastive Learning and Nonlinear ICA](https://mlsanity.com/paper/1605.06336/) (2016)
- [The Risks of Invariant Risk Minimization](https://mlsanity.com/paper/2010.05761/) (2020)
- [Causality for Machine Learning](https://mlsanity.com/paper/1911.10500/) (2019)
- [Weakly-Supervised Disentanglement Without Compromises](https://mlsanity.com/paper/2002.02886/) (2020)
- [Contrastive Learning Inverts the Data Generating Process](https://mlsanity.com/paper/2102.08850/) (2021)
- [Invariance Principle Meets Information Bottleneck for Out-of-Distribution Generalization](https://mlsanity.com/paper/2106.06607/) (2021)
- [Towards Causal Representation Learning](https://mlsanity.com/paper/2102.11107/) (2021)
- [Representation Learning via Invariant Causal Mechanisms](https://mlsanity.com/paper/2010.07922/) (2020)
- [Causal Discovery from Heterogeneous/Nonstationary Data with Independent Changes](https://mlsanity.com/paper/1903.01672/) (2019)
- [Disentanglement via Mechanism Sparsity Regularization: A New Principle for Nonlinear ICA](https://mlsanity.com/paper/2107.10098/) (2021)
- [A Meta-Transfer Objective for Learning to Disentangle Causal Mechanisms](https://mlsanity.com/paper/1901.10912/) (2019)
- [Weakly supervised causal representation learning](https://mlsanity.com/paper/2203.16437/) (2022)
- [Disentangled Representation Learning for Non-Parallel Text Style Transfer](https://mlsanity.com/paper/1808.04339/) (2018)
- [Towards Nonlinear Disentanglement in Natural Data with Temporal Sparse Coding](https://mlsanity.com/paper/2007.10930/) (2020)
- [Does Invariant Risk Minimization Capture Invariance?](https://mlsanity.com/paper/2101.01134/) (2021)
- [Robustly Disentangled Causal Mechanisms: Validating Deep Representations for Interventional Robustness](https://mlsanity.com/paper/1811.00007/) (2018)
- [On Linear Identifiability of Learned Representations](https://mlsanity.com/paper/2007.00810/) (2020)
- [Independent mechanism analysis, a new concept?](https://mlsanity.com/paper/2106.05200/) (2021)
- [The Incomplete Rosetta Stone Problem: Identifiability Results for Multi-View Nonlinear ICA](https://mlsanity.com/paper/1905.06642/) (2019)

## Built on by (most cited first, 3 of 3)

- [A Generative Model of Symmetry Transformations](https://mlsanity.com/paper/2403.01946/) (2024)
- [What Makes a Representation Good for Single-Cell Perturbation Prediction?](https://mlsanity.com/paper/2605.19343/) (2026)
- [Whole-Genome Phenotype Prediction with Machine Learning: Open Problems in Bacterial Genomics](https://mlsanity.com/paper/2502.07749/) (2025)

## Abstract (arXiv)

This paper presents a novel approach that leverages domain variability to learn representations that are conditionally invariant to unwanted variability or distractors. Our approach identifies both spurious and invariant latent features necessary for achieving accurate reconstruction by placing distinct conditional priors on latent features. The invariant signals are disentangled from noise by enforcing independence which facilitates the construction of an interpretable model with a causal semantic. By exploiting the interplay between data domains and labels, our method simultaneously identifies invariant features and builds invariant predictors. We apply our method to grand biological challenges, such as data integration in single-cell genomics with the aim of capturing biological variations across datasets with many samples, obtained from different conditions or multiple laboratories. Our approach allows for the incorporation of specific biological mechanisms, including gene programs, disease states, or treatment conditions into the data integration process, bridging the gap between the theoretical assumptions and real biological applications. Specifically, the proposed approach helps to disentangle biological signals from data biases that are unrelated to the target task or the causal explanation of interest. Through extensive benchmarking using large-scale human hematopoiesis and human lung cancer data, we validate the superiority of our approach over existing methods and demonstrate that it can empower deeper insights into cellular heterogeneity and the identification of disease cell states.