FL-Sailer: Efficient and Privacy-Preserving Federated Learning for Scalable Single-Cell Epigenetic Data Analysis via Adaptive Sampling
Authors: Guangyi Zhang, Yi Dai, Yiyun He, Junhao Liu
Organizations: Department of Computer Science, University of California, Irvine · Department of Mathematics, University of California, San Diego
Abstract
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.
Federated learning (FL) enables collaborative analysis of biomedical data without exchanging sensitive patient-level information, but its performance in multi-center studies may be compromised by batch effects which can obscure biological signals. Here, we systematically assess the impact of uncorrected batch effects on FL outcomes using four multi-center omics datasets, including transcriptomic, proteomic, and metabolomic data, and two representative algorithms: federated k-means clustering and federated random forest classification. Our results demonstrate that uncorrected batch effects undermine unsupervised FL and can substantially degrade supervised FL performance, indicating that privacy-aware batch-effect correction is essential for reliable FL. To enable privacy-preserving BEC in distributed bulk omics data, we introduce fedRBE ( https://featurecloud.ai/app/fedrbe ), a federated implementation of limma's removeBatchEffect() method enhanced by secure multi-party computation, suitable for datasets with missing values and non-identical feature sets across clients, including proteomics and metabolomics data.
Yuliya Burankova, Julian Klemm, Jens J. G. Lohmann +5
There are two categories of methods in Federated Learning (FL) for joint training across multiple clients: (i) parallel FL (PFL), where clients train models in a parallel manner; and (ii) sequential FL (SFL), where clients train models in a sequential manner. In contrast to that of PFL, the convergence theory of SFL on heterogeneous data is still lacking. In this paper, we establish the convergence guarantees of SFL for strongly/general/non-convex objectives on heterogeneous data. The convergence guarantees of SFL are better than that of PFL on heterogeneous data with both full and partial client participation. Experimental results validate the counterintuitive analysis result that SFL outperforms PFL on extremely heterogeneous data in cross-device settings.
Security and privacy are primordial requirements for Federated Learning (FL), especially in fields such as healthcare and genomics where sensitive information has to be analyzed. Our FL framework is designed to address these challenges while proposing a modular, flexible and micro-service architecture. More precisely, it integrates an efficient gRPC communication layer and a Finite State Machine to ensure robust component synchronization and threat detection, while relying on a fault-tolerant secure aggregation protocol using a Threshold variant of the CKKS homomorphic cryptosystem. This allows blind model aggregation by an orchestration server, requiring a minimum of t-out-of-N active clients for decryption while minimizing communication overhead thanks to both cryptographic and network protocols. We ensure IND-CPA-D security through noise flooding and mitigate the recent key-recovery attack on synchronized decryptors by renewing the collective key material at every round. We demonstrate the framework's effectiveness through diverse use cases, ranging from standard image recognition (EMNIST) to complex genomic classification including breast cancer subtyping on TCGA, evaluating system performance across different threshold values and model scales.
Paul Largillier, Karl Paygambar, Cédric Gouy-Pailler +3