Gene regulatory network inference (GRNI) aims to discover how genes causally regulate each other from gene expression data. It is well-known that statistical dependencies in observed data do not necessarily imply causation, as spurious dependencies may arise from, such as non-coding RNAs. Numerous GRNI methods have thus been proposed to address this confounding issue. However, dependencies may also result from --only cells satisfying certain survival or inclusion criteria are observed--while these selection-induced spurious dependencies are frequently overlooked in gene expression data analyses. In this work, we show that such selection is ubiquitous and, when ignored or conflated with true regulations, can lead to flawed causal interpretation and misguided intervention recommendations. To address this challenge, a fundamental question arises: can we distinguish dependencies due to regulation, confounding, and crucially, selection? We show that gene perturbations offer a simple yet effective answer: selection-induced dependencies are under perturbation, while those from regulation or confounding are not. Building on this motivation, we propose GISL (Gene regulatory network Inference in the presence of Selection bias and Latent confounders), a principled algorithm that leverages perturbation data to uncover both true gene regulatory relations and non-regulatory mechanisms of selection and confounding up to the equivalence class. Experiments on synthetic and real-world gene expression data demonstrate the effectiveness of our method.

We consider the problem of clustering nested or hierarchical data, where observations are grouped and there are both group-level and observation-level variables. In our motivating OneK1K dataset, observations consist of single-cell RNA-sequencing (scRNA-seq) data from 982 individuals (groups), totaling 1.27 million cells (observations), along with individual-specific genotype data. This type of data would enable the identification of cell types and the investigation of how genetic variations among individuals influence differences in cell-type profiles. Our goal, therefore, is to jointly cluster cells and individuals to capture the heterogeneity across both levels using cell-specific gene expressions as well as individual-specific genotypes. However, existing grouped clustering methods do not incorporate group-level variables, thereby limiting their ability to capture the heterogeneity of genotypes in our motivating application. To address this, we propose the Nested Atoms Model (NAM), a new Bayesian nonparametric approach that enables the desired two-layered clustering, accounting for both group-level and observation-level variables. To scale NAM for high-dimensional data, we develop a fast variational Bayesian inference algorithm. Simulations show that NAM outperforms existing methods that ignore group-level variables. Applied to the OneK1K dataset, NAM identifies clusters of genetically similar individuals with homogeneous cell-type profiles. The resulting cell clusters align with known immune cell types based on differential gene expression, underscoring the ability of NAM to capture nested heterogeneity and provide biologically meaningful insights.

However, the undirected setting is often insufficient: only a causal (i.e., directed) network provides

Biclustering is an essential unsupervised machine learning technique for simultaneously clustering rows and columns of a data matrix, with widespread applications in genomics, transcriptomics, and other high-dimensional omics data. Despite its importance, existing biclustering methods struggle to meet the demands of modern large-scale datasets. The challenges stem from the accumulation of noise in high-dimensional features, the limitations of non-convex optimization formulations, and the computational complexity of identifying meaningful biclusters. These issues often result in reduced accuracy and stability as the size of the dataset increases. To overcome these challenges, we propose Sparse Convex Biclustering (SpaCoBi), a novel method that penalizes noise during the biclustering process to improve both accuracy and robustness. By adopting a convex optimization framework and introducing a stability-based tuning criterion, SpaCoBi achieves an optimal balance between cluster fidelity and sparsity. Comprehensive numerical studies, including simulations and an application to mouse olfactory bulb data, demonstrate that SpaCoBi significantly outperforms state-of-the-art methods in accuracy. These results highlight SpaCoBi as a robust and efficient solution for biclustering in high-dimensional and large-scale datasets.

In this paper, we present two algorithms of this type and prove that both are consistent under the faithfulness assumption.

However, the undirected setting is often insufficient: only a causal (i.e., directed) network provides

Computational modeling of single-cell gene expression is crucial for understanding cellular processes, but generating realistic expression profiles remains a major challenge. This difficulty arises from the count nature of gene expression data and complex latent dependencies among genes. Existing generative models often impose artificial gene orderings or rely on shallow neural network architectures. We introduce a scalable latent diffusion model for single-cell gene expression data, which we refer to as scLDM, that respects the fundamental exchangeability property of the data. Our VAE uses fixed-size latent variables leveraging a unified Multi-head Cross-Attention Block (MCAB) architecture, which serves dual roles: permutation-invariant pooling in the encoder and permutation-equivariant unpooling in the decoder. We enhance this framework by replacing the Gaussian prior with a latent diffusion model using Diffusion Transformers and linear interpolants, enabling high-quality generation with multi-conditional classifier-free guidance. We show its superior performance in a variety of experiments for both observational and perturbational single-cell data, as well as downstream tasks like cell-level classification.

Recent advances in multi-modal algorithms have driven and been driven by the increasing availability of large image-text datasets, leading to significant strides in various fields, including computational pathology.

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