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

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.

Minimax optimal differentially private synthetic data for smooth queries

Differentially private synthetic data enables the sharing and analysis of sensitive datasets while providing rigorous privacy guarantees for individual contributors. A central challenge is to achieve strong utility guarantees for meaningful downstream analysis. Many existing methods ensure uniform accuracy over broad query classes, such as all Lipschitz functions, but this level of generality often leads to suboptimal rates for statistics of practical interest. Since many common data analysis queries exhibit smoothness beyond what worst-case Lipschitz bounds capture, we ask whether exploiting this additional structure can yield improved utility. We study the problem of generating $(\varepsilon,δ)$-differentially private synthetic data from a dataset of size $n$ supported on the hypercube $[-1,1]^d$, with utility guarantees uniformly for all smooth queries having bounded derivatives up to order $k$. We propose a polynomial-time algorithm that achieves a minimax error rate of $n^{-\min \{1, \frac{k}{d}\}}$, up to a $\log(n)$ factor. This characterization uncovers a phase transition at $k=d$. Our results generalize the Chebyshev moment matching framework of (Musco et al., 2025; Wang et al., 2016) and strictly improve the error rates for $k$-smooth queries established in (Wang et al., 2016). Moreover, we establish the first minimax lower bound for the utility of $(\varepsilon,δ)$-differentially private synthetic data with respect to $k$-smooth queries, extending the Wasserstein lower bound for $\varepsilon$-differential privacy in (Boedihardjo et al., 2024).

Online Differentially Private Synthetic Data Generation

We present a polynomial-time algorithm for online differentially private synthetic data generation. For a data stream within the hypercube $[0,1]^d$ and an infinite time horizon, we develop an online algorithm that generates a differentially private synthetic dataset at each time $t$. This algorithm achieves a near-optimal accuracy bound of $O(t^{-1/d}\log(t))$ for $d\geq 2$ and $O(t^{-1}\log^{4.5}(t))$ for $d=1$ in the 1-Wasserstein distance. This result generalizes the previous work on the continual release model for counting queries to include Lipschitz queries. Compared to the offline case, where the entire dataset is available at once, our approach requires only an extra polylog factor in the accuracy bound.

Differentially private low-dimensional representation of high-dimensional data

Differentially private synthetic data provide a powerful mechanism to enable data analysis while protecting sensitive information about individuals. However, when the data lie in a high-dimensional space, the accuracy of the synthetic data suffers from the curse of dimensionality. In this paper, we propose a differentially private algorithm to generate low-dimensional synthetic data efficiently from a high-dimensional dataset with a utility guarantee with respect to the Wasserstein distance. A key step of our algorithm is a private principal component analysis (PCA) procedure with a near-optimal accuracy bound that circumvents the curse of dimensionality. Different from the standard perturbation analysis using the Davis-Kahan theorem, our analysis of private PCA works without assuming the spectral gap for the sample covariance matrix.