# A Proper Scoring Rule for Virtual Staining

arXiv: https://arxiv.org/abs/2602.23305 · HTML: https://mlsanity.com/paper/2602.23305/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 16 of its 33 references that are in the map.
- First posted on arXiv 26 Feb 2026.

## Builds on (most cited first, 16 of 16)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Large Scale GAN Training for High Fidelity Natural Image Synthesis](https://mlsanity.com/paper/1809.11096/) (2018)
- [Image Super-Resolution via Iterative Refinement](https://mlsanity.com/paper/2104.07636/) (2021)
- [Palette: Image-to-Image Diffusion Models](https://mlsanity.com/paper/2111.05826/) (2021)
- [High-Resolution Image Synthesis and Semantic Manipulation with Conditional GANs](https://mlsanity.com/paper/1711.11585/) (2017)
- [A Note on the Inception Score](https://mlsanity.com/paper/1801.01973/) (2018)
- [Conditional Image Generation with Score-Based Diffusion Models](https://mlsanity.com/paper/2111.13606/) (2021)
- [Fr'echet ChemNet Distance: A metric for generative models for molecules in drug discovery](https://mlsanity.com/paper/1803.09518/) (2018)
- [Conditional Frechet Inception Distance](https://mlsanity.com/paper/2103.11521/) (2021)
- [Uncertainty-Guided Progressive GANs for Medical Image Translation](https://mlsanity.com/paper/2106.15542/) (2021)
- [Variational Autoencoder Generative Adversarial Network for Synthetic Data Generation in Smart Home](https://mlsanity.com/paper/2201.07387/) (2022)
- [Can virtual staining for high-throughput screening generalize?](https://mlsanity.com/paper/2407.06979/) (2024)

## Abstract (arXiv)

Generative virtual staining (VS) models for high-throughput screening (HTS) can provide an estimated posterior distribution of possible biological feature values for each input and cell. However, when evaluating a VS model, the true posterior is unavailable. Existing evaluation protocols only check the accuracy of the marginal distribution over the dataset rather than the predicted posteriors. We introduce information gain (IG) as a cell-wise evaluation framework that enables direct assessment of predicted posteriors. IG is a strictly proper scoring rule and comes with a sound theoretical motivation allowing for interpretability, and for comparing results across models and features. We evaluate diffusion- and GAN-based models on an extensive HTS dataset using IG and other metrics and show that IG can reveal substantial performance differences other metrics cannot.