# HASSL: Hierarchy-Aware Self-Supervised Learning Framework for Single Cell Microscopy

arXiv: https://arxiv.org/abs/2607.04353 · HTML: https://mlsanity.com/paper/2607.04353/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 26 of its 59 references that are in the map.
- First posted on arXiv 5 Jul 2026.

## Builds on (most cited first, 26 of 26)

- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [Momentum Contrast for Unsupervised Visual Representation Learning](https://mlsanity.com/paper/1911.05722/) (2019)
- [Emerging Properties in Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.14294/) (2021)
- [Bootstrap your own latent: A new approach to self-supervised Learning](https://mlsanity.com/paper/2006.07733/) (2020)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Unsupervised Learning of Visual Features by Contrasting Cluster Assignments](https://mlsanity.com/paper/2006.09882/) (2020)
- [FaceNet: A Unified Embedding for Face Recognition and Clustering](https://mlsanity.com/paper/1503.03832/) (2015)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Unsupervised Feature Learning via Non-Parametric Instance-level Discrimination](https://mlsanity.com/paper/1805.01978/) (2018)
- [DINOv3](https://mlsanity.com/paper/2508.10104/) (2025)
- [Prototypical Contrastive Learning of Unsupervised Representations](https://mlsanity.com/paper/2005.04966/) (2020)
- [PanNuke Dataset Extension, Insights and Baselines](https://mlsanity.com/paper/2003.10778/) (2020)
- [Methods for Segmentation and Classification of Digital Microscopy Tissue Images](https://mlsanity.com/paper/1810.13230/) (2018)
- [Masked Autoencoders for Microscopy are Scalable Learners of Cellular Biology](https://mlsanity.com/paper/2404.10242/) (2024)
- [CryoNuSeg: A Dataset for Nuclei Instance Segmentation of Cryosectioned H&E-Stained Histological Images](https://mlsanity.com/paper/2101.00442/) (2021)
- [CoNIC: Colon Nuclei Identification and Counting Challenge 2022](https://mlsanity.com/paper/2111.14485/) (2021)
- [HCSC: Hierarchical Contrastive Selective Coding](https://mlsanity.com/paper/2202.00455/) (2022)
- [The Multi-modality Cell Segmentation Challenge: Towards Universal Solutions](https://mlsanity.com/paper/2308.05864/) (2023)
- [NuInsSeg: A Fully Annotated Dataset for Nuclei Instance Segmentation in H&E-Stained Histological Images](https://mlsanity.com/paper/2308.01760/) (2023)
- [ChAda-ViT : Channel Adaptive Attention for Joint Representation Learning of Heterogeneous Microscopy Images](https://mlsanity.com/paper/2311.15264/) (2023)
- [Weakly Supervised Set-Consistency Learning Improves Morphological Profiling of Single-Cell Images](https://mlsanity.com/paper/2406.05308/) (2024)
- [Metadata-guided Consistency Learning for High Content Images](https://mlsanity.com/paper/2212.11595/) (2022)
- [Contrastive Hierarchical Clustering](https://mlsanity.com/paper/2303.03389/) (2023)

## Abstract (arXiv)

Hierarchical structure is common in image data, where fine-grained clusters often merge into larger, coarser semantic groups. In biological cell images, current self-supervised learning models often suppress this hierarchy, as coarse factors such as imaging modality can obscure finer morphological attributes in the latent space. We propose a hierarchy-aware self-supervised training framework to address this problem. Our method combines two components: a distillation framework with a segmentation teacher to improve morphological awareness in the latent space, and a hierarchy-aware contrastive loss based on HDBSCAN to improve decision boundaries between closely related subtypes at different hierarchical levels. Together, these components reduce the tendency of self-supervised learning to overemphasize coarse factors and instead align embeddings with semantic and morphological cues. This yields biologically meaningful sub-clusters driven by fine morphological detail. We train and evaluate our method on a curated corpus of 2.3 million single cells aggregated from 20 microscopy datasets, both labeled and unlabeled, covering 208 cell classes. Our method improves over baseline and counterpart methods, increasing average top-K accuracy by 2.8%, top-9 retrieval on the dataset with the deepest hierarchy by 6.3%, and downstream F1-score for biologically relevant drug classification from perturbed cell morphology by 7.8%.