# Pretraining and Distillation Matter More Than Architecture Family for Label-Free Single-Cell Classification

arXiv: https://arxiv.org/abs/2609.09863 · HTML: https://mlsanity.com/paper/2609.09863/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Distillation for medical imaging, one of 12 directions in Knowledge distillation.
- Builds on 5 of its 11 references that are in the map.
- First posted on arXiv 9 Sep 2026.

## Placed in

- Knowledge distillation / [Distillation for medical imaging](https://mlsanity.com/distill/distillation-for-medical-imaging/)

## Builds on (most cited first, 5 of 5)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Distilling the Knowledge in a Neural Network](https://mlsanity.com/paper/1503.02531/) (2015)
- [EfficientNet: Rethinking Model Scaling for Convolutional Neural Networks](https://mlsanity.com/paper/1905.11946/) (2019)
- [Training data-efficient image transformers & distillation through attention](https://mlsanity.com/paper/2012.12877/) (2020)
- [Do Vision Transformers See Like Convolutional Neural Networks?](https://mlsanity.com/paper/2108.08810/) (2021)

## Abstract (arXiv)

Choosing a deep learning architecture for label-free single-cell classification remains an open question, with microscopy benchmarks reporting conflicting conclusions about CNNs versus transformers. We present a controlled benchmark on LIVECell phase-contrast microscopy data using source-image-disjoint train/validation/test splits to prevent parent-image leakage and matched optimisation, augmentation, and evaluation protocols across EfficientNet, Vision Transformer (ViT), and EVA-02 models. This allows the effects of architecture, pretraining, fine-tuning, tokenisation, and distillation to be disentangled. We find that the previously reported CNN advantage is largely explained by pretraining rather than architecture: the smallest pretrained model outperforms the strongest model trained from scratch despite far fewer parameters. Pretraining improves macro-F1 by 3-4 points, while the gap between the best pretrained CNN and transformer is below 0.5 points. Architectural choices nevertheless matter: ViT-S/8 outperforms ViT-S/16 and matches the four-times-larger ViT-B/16 at a quarter of the parameters, showing that finer tokenisation benefits small cell crops. Conversely, layer-wise learning-rate decay, central to the EVA-02 fine-tuning recipe, degrades performance, highlighting that transfer heuristics from natural-image recognition may not generalise to microscopy. Finally, knowledge distillation substantially improves the deployment frontier: compact EfficientNet-B0 students distilled from teacher councils outperform every individually trained backbone, including the EfficientNet-B5 and EVA-02 teachers. Overall, our results show that rigorous control of pretraining and evaluation is essential for interpreting biomedical architecture benchmarks, while distillation may be a more effective route to practical single-cell classification than architecture choice alone.