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

arXiv.org Machine Learning

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.


From Video-to-PDE: Data-Driven Discovery of Nonlinear Dye Plume Dynamics

arXiv.org Machine Learning

Inferring continuum models directly from video is hampered by two facts: the recorded field is uncalibrated image intensity rather than a physical state, and direct numerical differentiation of noisy frames is unstable. We develop a video-to-PDE pipeline that converts grayscale recordings of an ink plume into a normalised scalar field $u(x,y,t)$, isolates a bulk drift $\mathbf{v}(t)$ from intrinsic spreading via the intensity-weighted centroid, and identifies an effective transport law by weak-form sparse regression. Conditioning, threshold-sweep and random-centre diagnostics show that overcomplete libraries are strongly collinear; the search is therefore restricted to compact gradient-based libraries. Coefficients are refined by an inverse physics-informed network and recalibrated against forward rollouts, with a chronological block bootstrap quantifying uncertainty. The selected reduced model $u_t+\mathbf v(t)\!\cdot\!\nabla u = 9.005\,|\nabla u|^{2}+0.666\,ฮ”u$ outperforms advection--diffusion baselines on held-out frames, retains a positive Laplacian coefficient, and admits a Cole--Hopf reduction to a linear advection--diffusion equation. The framework demonstrates that uncalibrated visual data can yield compact, predictive and structurally interpretable continuum models when discovery, calibration and uncertainty are treated as distinct stages.


Confirmation of Binary Clustering in Gamma-Ray Bursts through an Integrated $p$-value from Multiple Nonparametric Tests of Hypotheses

arXiv.org Machine Learning

The paper applies a new, nonparametric, interpoint distance-based measure to confirm the inherent groups prevailing in the brightest source of light in the universe: gamma-ray bursts. Our effective metric, in association with clustering methods like Gaussian-mixture model-based and $K$-means algorithms, resolves the conflict regarding the possibility about existence of more than binary clusters in the gamma-ray burst population. Here we carry out multiple nonparametric statistical tests of hypotheses, as many as the number of bursts available from the `BATSE' catalog. An integrated $p$-value achieved from the aforesaid dependent tests solves our concern confirming two groups of short and long bursts.


PAIR-CI: Calibrated Conditional Independence Testing for Causal Discovery with Incomplete Data

arXiv.org Machine Learning

The standard constraint-based paradigm for causal discovery with incomplete data -- impute first, test second -- is frequently miscalibrated: any consistent conditional independence (CI) test rejects a true null with probability approaching 1 when imputation error induces spurious conditional dependence. We introduce PAIR-CI, a nonparametric CI test that restores calibration by integrating multiple imputation directly into the inferential procedure via a paired permutation design. PAIR-CI compares cross-validated models that include and exclude the candidate variable while receiving the same imputed conditioning set, forcing imputation error to cancel in their loss difference rather than contaminate the test statistic. A provably consistent variance estimator jointly accounts for uncertainty arising from cross-validation and multiple imputation -- to our knowledge, the first formal unification of these two inferential frameworks. In simulations, existing imputation-based CI tests exhibit false positive rates of 28--45% when data are missing not at random (MNAR), whereas PAIR-CI averages below the nominal 5% level across data-generating processes and missingness mechanisms. These gains are largest in nonlinear settings and grow with causal graph size: when integrated into the PC algorithm, PAIR-CI reduces structural Hamming distance by 8% on 10-variable nonlinear graphs, 15% on 30-variable equivalents, and up to 44% on the 56-variable HAILFINDER network, with stable performance in all settings.


Self-Attention as Transport: Limits of Symmetric Spectral Diagnostics

arXiv.org Machine Learning

Large language models hallucinate in predictable ways: attention routing fails by over-concentrating on a narrow set of positions, or by spreading so diffusely that relevance is diluted, and the shape of the failure carries diagnostic signal. A widely used family of spectral methods analyzes the symmetric component of the degree-normalized attention operator, which governs transport capacity; we prove that every transpose-invariant spectral diagnostic of this operator is structurally orientation-blind (it cannot distinguish an operator from its transpose, and therefore cannot detect information-flow direction), with a quantitative converse establishing the asymmetry coefficient $G$ as the unique control parameter for direction. Pairing this with a closed-form bipartite-Cheeger landscape for canonical causal architectures, we show that uniform causal attention satisfies an $n$-independent floor $ฯ•\ge 1/5$ with worst cut at $t^\ast/n \approx 0.32$, while window attention pierces the floor as $O(w/n)$; failure modes are shape-different, not just value-different. The resulting two-axis diagnostic ($ฯ•$ for capacity, $G$ for direction) yields a falsifiable polarity prediction: bottleneck- and diffuse-dominated benchmarks should exhibit opposite polarity. Under length-controlled evaluation, transport features retain interpretable signal (LC-AUROC from 0.62 to 0.84) on tested models up to 8B parameters, with polarity reversing as predicted between HaluEval and MedHallu.


Regime-Conditioned Evaluation in Multi-Context Bayesian Optimization

arXiv.org Machine Learning

Published transfer-BO comparisons often estimate an average treatment effect of acquisition choice over hidden regime variables, while practitioners need the conditional effect for their specific prior quality, budget ratio, and metric. An audit of 40 transfer-BO papers from NeurIPS, ICML, ICLR, AISTATS, UAI, TMLR, JMLR, and AutoML-Conf (2022-2025) finds that 98% never vary B/|A| as a controlled axis. On the same GDSC2 benchmark, changing only the budget reverses the ranking: at B=50, Greedy outperforms UCB by 0.050 Hit@1, while at B=100, UCB outperforms Greedy by 0.035. We capture this transition with the Portable Regime Score PRS=(B/|A|)(1-rho), where rho is the prior rank correlation and can be estimated from pilot contexts before the main comparison. Across 79 conditions spanning chemistry, drug-response biology, and HPO, a hierarchical model gives beta=0.50 (p=1.1e-9), and 19% of conditions fall in an equivalence zone where |advantage|<0.01 Hit@1. In five published reversal cases, PRS predicts the winner from pre-comparison observables. A No-Free-Leaderboard proposition explains why unconditional rankings are unstable: when CATE changes sign across regimes, the reported ATE becomes a function of benchmark mixture. RegimePlanner, which estimates rho online and switches acquisition accordingly, wins all 16 HPO-B search spaces at B=100 and exceeds the matched {Greedy,UCB} per-context oracle on GDSC2 by 18%. Pre-registered predictions achieve 27/40=67.5% overall accuracy and above 90% within EMA prior families. The practical protocol is simple: report B/|A|, rho, K, and metric alongside any claimed acquisition advantage.


When Does Gene Regulatory Network Inference Break? A Controlled Diagnostic Study of Causal and Correlational Methods on Single-Cell Data

arXiv.org Machine Learning

Despite theoretical advantages, causal methods for Gene Regulatory Network (GRN) inference from single-cell RNA-seq data consistently fail to match or outperform correlation-based baselines in many realistic benchmarks, a persistent puzzle which casts doubt on the value of causality for this task. We argue that existing benchmarks are insufficiently controlled to answer this question because they evaluate on real or semi-real data where multiple pathologies co-occur, confounding failure modes, and obscuring the specific conditions under which different inference methods excel or fail. To address this gap, we introduce a controlled diagnostic framework that isolates seven biologically motivated pathologies (dropout, latent confounders, cell-type mixing, feedback loops, network density, sample size, and pseudotime drift) and measure how six representative methods spanning three inference paradigms degrade as each pathology intensifies. Across 6,120 controlled experiments, we find that causal methods genuinely dominate in clean and structurally favorable regimes, but specific pathologies (notably dropout and latent confounders) selectively neutralize their advantages. We further introduce an errortype decomposition that reveals methods with similar aggregate accuracy commit qualitatively different errors. To probe whether single-pathology effects persist when multiple stressors co-occur, we perform an interaction sweep over the three most impactful pathologies and find that their joint effects are sub-additive, while also exposing density-conditional cross-overs invisible to single-dial analysis. Our findings offer a nuanced understanding of when and why different methods succeed or fail for GRN inference, providing actionable insights for method development and practical guidance for practitioners.3


Jacobian-Velocity Bounds for Deployment Risk Under Covariate Drift

arXiv.org Machine Learning

We study long-horizon deployment of a frozen predictor under dynamic covariate shift. A time-domain Poincarรฉ inequality reduces temporal risk volatility to derivative energy, and a Jacobian-velocity theorem identifies directional tangent energy along the deployment path as the governing quantity under explicit along-path regularity and domination assumptions. Under low-rank drift, that quantity reduces to directional Jacobian energy in the drift subspace, motivating drift-aligned tangent regularization (DTR) and a matched monitoring proxy. Rather than smoothing the network isotropically, DTR penalizes sensitivity only along estimated drift directions. We validate the theorem-to-method pipeline in four experiments: a synthetic benchmark for the time-domain inequality, a controlled synthetic comparison against isotropic Jacobian regularization, and two frozen-deployment studies on the UCI Air Quality and Tetouan power-consumption datasets. DTR reduces risk volatility and directional gain in the controlled low-rank regime, beats isotropic smoothing there, and gives validation-selected deployment gains on both real datasets when the Air Quality drift subspace is estimated from target-orthogonal sensor motion. Moderate drift-subspace misspecification is tolerable while orthogonal misspecification largely removes the benefit.


Adaptivity Under Realizability Constraints: Comparing In-Context and Agentic Learning

arXiv.org Machine Learning

We compare in-context learning with fixed queries and agentic learning with adaptive queries for uniform approximation of task families. We consider two settings: an unrestricted regime, where querying and approximation are arbitrary functions, and a realizable regime, where we require these operations to be implemented by ReLU neural networks. In both settings, adaptivity never hinders approximation performance. However, this advantage can change when one passes from the unrestricted regime to the realizable regime. We identify four distinct approximation scenarios, each witnessed by an explicit task family: (a) no advantage of adaptivity; (b) an advantage in the unrestricted regime that persists under ReLU realizability; (c) an advantage that arises only under realizability; and (d) an advantage that disappears under realizability. This demonstrates that representational constraints interact profoundly with the effect of adaptivity.


Scalable inference of spatial regions and temporal signatures from time series

arXiv.org Machine Learning

Regionalization aims to partition a spatial domain into contiguous regions that share similar characteristics, enabling more effective spatial analysis, policy making, and resource management. Existing approaches for spatial regionalization typically rely on static spatial snapshots rather than evolving time series. Meanwhile, most time series clustering methods ignore spatial structure or enforce spatial continuity through ad hoc regularization, constraining the number of inferred regions a priori either explicitly or implicitly. Utilizing the minimum description length principle from information theory, here we propose an efficient and fully nonparametric framework for the regionalization of spatial time series. Our method jointly infers a spatial partition along with a set of representative time series archetypes ("drivers") that best compress a spatiotemporal dataset, with a runtime log-linear in the number of time series. We demonstrate that this method can accurately recover planted regional structure and drivers in synthetic time series, and can extract meaningful structural regularities in large-scale empirical air quality and vegetation index records. Our method provides a principled and scalable framework for spatially contiguous partitioning, allowing interpretable temporal patterns and homogeneous regions to emerge directly from the data itself.