❌

Reading view

AI-guided multi-omics analysis identifies NPC1-modulated susceptibility to SARS-CoV-2 infection under PM(2.5) exposure

Nat Commun. 2026 Mar 30. doi: 10.1038/s41467-026-71196-3. Online ahead of print.

ABSTRACT

Exposure to airborne fine particulate matter (PM2.5) has been linked to increased risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet the underlying mechanisms remain unclear. Here, by leveraging a fine-tuned foundation model of single-cell transcriptomics, we uncover shared transcriptional signatures between PM2.5 exposure and SARS-CoV-2 infection. We further validate this association using population-level epidemiological analyses and perform genome-wide association studies (GWAS) to identify genetic variants that modulate infection risk under PM2.5 exposure. In addition, we identify NPC1 as a key modulator involved in SARS-CoV-2 infection efficiency under virus-laden PM2.5 exposure through integrative functional genomic analyses and in vitro experiments. Our findings suggest that PM2.5 facilitates viral entry through an NPC1-modulated endo-lysosomal pathway, providing a mechanistic explanation for observed pollution-related susceptibility. By integrating artificial intelligence (AI)-guided transcriptomics, epidemiology, GWAS, functional genomics, and in vitro verification, our study elucidates how environmental and genetic factors jointly influence SARS-CoV-2 susceptibility. This work highlights how AI-assisted multi-omics integration systematically decodes the health impacts of environmental exposures from molecular to population levels and informs air quality policy and infectious disease preparedness.

PMID:41912520 | DOI:10.1038/s41467-026-71196-3

  •  

Taming Preconditioner Drift: Unlocking the Potential of Second-Order Optimizers for Federated Learning on Non-IID Data

arXiv:2602.19271v1 Announce Type: cross Abstract: Second-order optimizers can significantly accelerate large-scale training, yet their naive federated variants are often unstable or even diverge on non-IID data. We show that a key culprit is \emph{preconditioner drift}: client-side second-order training induces heterogeneous \emph{curvature-defined geometries} (i.e., preconditioner coordinate systems), and server-side model averaging updates computed under incompatible metrics, corrupting the global descent direction. To address this geometric mismatch, we propose \texttt{FedPAC}, a \emph{preconditioner alignment and correction} framework for reliable federated second-order optimization. \texttt{FedPAC} explicitly decouples parameter aggregation from geometry synchronization by: (i) \textbf{Alignment} (i.e.,aggregating local preconditioners into a global reference and warm-starting clients via global preconditioner); and (ii) \textbf{Correction} (i.e., steering local preconditioned updates using a global preconditioned direction to suppress long-term drift). We provide drift-coupled non-convex convergence guarantees with linear speedup under partial participation. Empirically, \texttt{FedPAC} consistently improves stability and accuracy across vision and language tasks, achieving up to $5.8\%$ absolute accuracy gain on CIFAR-100 with ViTs. Code is available at https://anonymous.4open.science/r/FedPAC-8B24.
  •  

Rethinking LoRA for Privacy-Preserving Federated Learning in Large Models

arXiv:2602.19926v1 Announce Type: cross Abstract: Fine-tuning large vision models (LVMs) and large language models (LLMs) under differentially private federated learning (DPFL) is hindered by a fundamental privacy-utility trade-off. Low-Rank Adaptation (LoRA), a promising parameter-efficient fine-tuning (PEFT) method, reduces computational and communication costs by introducing two trainable low-rank matrices while freezing pre-trained weights. However, directly applying LoRA in DPFL settings leads to performance degradation, especially in LVMs. Our analysis reveals three previously underexplored challenges: (1) gradient coupling caused by the simultaneous update of two asymmetric low-rank matrices, (2) compounded noise amplification under differential privacy, and (3) sharpness of the global aggregated model in the parameter space. To address these issues, we propose LA-LoRA (\textbf{L}ocal \textbf{A}lternating \textbf{LoRA}), a novel approach that decouples gradient interactions and aligns update directions across clients to enhance robustness under stringent privacy constraints. Theoretically, LA-LoRA strengthens convergence guarantees in noisy federated environments. Extensive experiments demonstrate that LA-LoRA achieves state-of-the-art (SOTA) performance on Swin Transformer and RoBERTa models, showcasing robustness to DP noise and broad applicability across both LVMs and LLMs. For example, when fine-tuning the Swin-B model on the Tiny-ImageNet dataset under a strict privacy budget ($\epsilon = 1$), LA-LoRA outperforms the best baseline, RoLoRA, by 16.83\% in test accuracy. Code is provided in \repolink.
  •  

DP-FedAdamW: An Efficient Optimizer for Differentially Private Federated Large Models

arXiv:2602.19945v1 Announce Type: cross Abstract: Balancing convergence efficiency and robustness under Differential Privacy (DP) is a central challenge in Federated Learning (FL). While AdamW accelerates training and fine-tuning in large-scale models, we find that directly applying it to Differentially Private FL (DPFL) suffers from three major issues: (i) data heterogeneity and privacy noise jointly amplify the variance of second-moment estimator, (ii) DP perturbations bias the second-moment estimator, and (iii) DP amplify AdamW sensitivity to local overfitting, worsening client drift. We propose DP-FedAdamW, the first AdamW-based optimizer for DPFL. It restores AdamW under DP by stabilizing second-moment variance, removing DP-induced bias, and aligning local updates to the global descent to curb client drift. Theoretically, we establish an unbiased second-moment estimator and prove a linearly accelerated convergence rate without any heterogeneity assumption, while providing tighter $(\varepsilon,\delta)$-DP guarantees. Our empirical results demonstrate the effectiveness of DP-FedAdamW across language and vision Transformers and ResNet-18. On Tiny-ImageNet (Swin-Base, $\varepsilon=1$), DP-FedAdamW outperforms the state-of-the-art (SOTA) by 5.83\%. The code is available in Appendix.
  •  
❌