# FL-Sailer: Efficient and Privacy-Preserving Federated Learning for Scalable Single-Cell Epigenetic Data Analysis via Adaptive Sampling

arXiv: https://arxiv.org/abs/2605.04519 · HTML: https://mlsanity.com/paper/2605.04519/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 31 references that are in the map.
- First posted on arXiv 6 May 2026.

## Builds on (most cited first, 8 of 8)

- [Communication-Efficient Learning of Deep Networks from Decentralized Data](https://mlsanity.com/paper/1602.05629/) (2016)
- [Federated Optimization in Heterogeneous Networks](https://mlsanity.com/paper/1812.06127/) (2018)
- [Adaptive Federated Optimization](https://mlsanity.com/paper/2003.00295/) (2020)
- [Tackling the Objective Inconsistency Problem in Heterogeneous Federated Optimization](https://mlsanity.com/paper/2007.07481/) (2020)
- [FedBN: Federated Learning on Non-IID Features via Local Batch Normalization](https://mlsanity.com/paper/2102.07623/) (2021)
- [Federated Learning Enables Big Data for Rare Cancer Boundary Detection](https://mlsanity.com/paper/2204.10836/) (2022)
- [Optimal CUR Matrix Decompositions](https://mlsanity.com/paper/1405.7910/) (2014)
- [A Convergence Theory for Federated Average: Beyond Smoothness](https://mlsanity.com/paper/2211.01588/) (2022)

## Abstract (arXiv)

Single-cell ATAC-seq (scATAC-seq) enables high-resolution mapping of chromatin accessibility, yet privacy regulations and data size constraints hinder multi-institutional sharing. Federated learning (FL) offers a privacy-preserving alternative, but faces three fundamental barriers in scATAC-seq analysis: ultra-high dimensionality, extreme sparsity, and severe cross-institutional heterogeneity. We propose FL-Sailer, the first FL framework designed for scATAC-seq data. FL-Sailer integrates two key innovations: (i) adaptive leverage score sampling, which selects biologically interpretable features while reducing dimensionality by 80%, and (ii) an invariant VAE architecture, which disentangles biological signals from technical confounders via mutual information minimization. We provide a convergence guarantee, showing that FL-Sailer converges to an approximate solution of the original high-dimensional problem with bounded error. Extensive experiments on synthetic and real epigenomic datasets demonstrate that FL-Sailer not only enables previously infeasible multi-institutional collaborations but also surpasses centralized methods by leveraging adaptive sampling as an implicit regularizer to suppress technical noise. Our work establishes that federated learning, when tailored to domain-specific challenges, can become a superior paradigm for collaborative epigenomic research.