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Flow-Based Density Ratio Estimation for Intractable Distributions with Applications in Genomics

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Estimating density ratios between pairs of intractable data distributions is a core problem in probabilistic modeling, enabling principled comparisons of sample likelihoods under different data-generating processes across conditions. While exact-likelihood models such as normalizing flows offer a promising approach to density ratio estimation, naive evaluations are computationally expensive and prone to discretization errors because they require simulating each distribution's likelihood independently. In this work, we leverage condition-aware flow matching to derive a single dynamical formulation for tracking density ratios along generative trajectories. We demonstrate competitive performance on simulated benchmarks for closed-form ratio estimation, and show that our method supports versatile tasks in single-cell genomics data analysis, where likelihood-based comparisons of cellular states across experimental conditions enable treatment effect estimation and batch correction evaluation.

Egor Antipov, Alessandro Palma, Lorenzo Consoli, Stephan G\"unnemann, Andrea Dittadi, Fabian J. Theis• 2026

Related benchmarks

TaskDatasetResultRank
Mutual Information EstimationStructured Gaussians d=40
MAE0.03
6
Mutual Information EstimationStructured Gaussians d=80
MAE0.02
6
Mutual Information EstimationStructured Gaussians d=160
MAE0.11
6
Mutual Information EstimationStructured Gaussians d=320
MAE1.16
6
Mutual Information EstimationStructured Gaussians d=20
MAE0.03
6
Single-cell Differential Abundance EstimationPBMC semi-synthetic 68k cells
Correlation (rho) for AUC1
5
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