Spatially variable genes (SVGs) are essential for elucidating tissue organization within spatially resolved transcriptomics. While a number of computational methods have been developed for SVG identification, their reliance on algorithm-specific assumptions, such as predefined kernel functions or spatial neighborhood graphs, often results in substantial variability in sensitivity and inflated false discovery rates (FDRs) across heterogeneous datasets. To address this challenge, we here develop Castl, an ensemble-based framework for SVG identification that integrates multiple detection methods through statistically designed aggregation modules. Comprehensive evaluations on both simulated and real-world data demonstrate that Castl consistently identifies biologically meaningful spatial expression patterns, mitigates method-specific biases and effectively controls FDRs across various biological contexts, resolutions, and spatial technologies. This flexible, assumption-free framework offers a robust and standardized foundation for spatially informed feature discovery in complex biological systems.

State-of-the-art systems neuroscience experiments yield large-scale multimodal data, and these data sets require new tools for analysis. Inspired by the success of large pretrained models in vision and language domains, we reframe the analysis of large-scale, cellular-resolution neuronal spiking data into an auto-regressive spatiotemporal generation problem. Neuroformer is a multimodal, multitask generative pre-trained transformer (GPT) model that is specifically designed to handle the intricacies of data in systems neuroscience. It scales linearly with feature size, can process an arbitrary number of modalities, and is adaptable to downstream tasks, such as predicting behavior. We first trained Neuroformer on simulated datasets, and found that it both accurately predicted simulated neuronal circuit activity, and also intrinsically inferred the underlying neural circuit connectivity, including direction. When pretrained to decode neural responses, the model predicted the behavior of a mouse with only few-shot fine-tuning, suggesting that the model begins learning how to do so directly from the neural representations themselves, without any explicit supervision. We used an ablation study to show that joint training on neuronal responses and behavior boosted performance, highlighting the model's ability to associate behavioral and neural representations in an unsupervised manner. These findings show that Neuroformer can analyze neural datasets and their emergent properties, informing the development of models and hypotheses associated with the brain.

The purpose of this paper is to infer a global (collective) model of time-varying responses of a set of nodes as a dynamic graph, where the individual time series are respectively observed at each of the nodes. The motivation of this work lies in the search for a connectome model which properly captures brain functionality upon observing activities in different regions of the brain and possibly of individual neurons. We formulate the problem as a quadratic objective functional of observed node signals over short time intervals, subjected to the proper regularization reflecting the graph smoothness and other dynamics involving the underlying graph’s Laplacian, as well as the time evolution smoothness of the underlying graph. The resulting joint optimization is solved by a continuous relaxation and an introduced novel gradient-projection scheme. We apply our algorithm to a real-world dataset comprising recorded activities of individual brain cells. The resulting model is shown to not only be viable but also efficiently computable.

Gaussian Process Factor Analysis (GPFA) has been broadly applied to the problem of identifying smooth, low-dimensional temporal structure underlying large-scale neural recordings. However, spike trains are non-Gaussian, which motivates combining GPFA with discrete observation models for binned spike count data. The drawback to this approach is that GPFA priors are not conjugate to count model likelihoods, which makes inference challenging. Here we address this obstacle by introducing a fast, approximate inference method for non-conjugate GPFA models. Our approach uses orthogonal second-order polynomials to approximate the nonlinear terms in the non-conjugate log-likelihood, resulting in a method we refer to as polynomial approximate log-likelihood (PAL) estimators. This approximation allows for accurate closed-form evaluation of marginal likelihoods and fast numerical optimization for parameters and hyperparameters. We derive PAL estimators for GPFA models with binomial, Poisson, and negative binomial observations and find the PAL estimation is highly accurate, and achieves faster convergence times compared to existing state-of-the-art inference methods. We also find that PAL hyperparameters can provide sensible initialization for black box variational inference (BBVI), which improves BBVI accuracy. We demonstrate that PAL estimators achieve fast and accurate extraction of latent structure from multi-neuron spike train data.

Neural datasets often contain measurements of neural activity across multiple trials of a repeated stimulus or behavior. An important problem in the analysis of such datasets is to characterize systematic aspects of neural activity that carry information about the repeated stimulus or behavior of interest, which can be considered signal'', and to separate them from the trial-to-trial fluctuations in activity that are not time-locked to the stimulus, which for purposes of such analyses can be considerednoise''. Gaussian Process factor models provide a powerful tool for identifying shared structure in high-dimensional neural data. However, they have not yet been adapted to the problem of characterizing signal and noise in multi-trial datasets. Here we address this shortcoming by proposing ``signal-noise'' Poisson-spiking Gaussian Process Factor Analysis (SNP-GPFA), a flexible latent variable model that resolves signal and noise latent structure in neural population spiking activity. To learn the parameters of our model, we introduce a Fourier-domain black box variational inference method that quickly identifies smooth latent structure. The resulting model reliably uncovers latent signal and trial-to-trial noise-related fluctuations in large-scale recordings. We use this model to show that in monkey V1, noise fluctuations perturb neural activity within a subspace orthogonal to signal activity, suggesting that trial-by-trial noise does not interfere with signal representations. Finally, we extend the model to capture statistical dependencies across brain regions in multi-region data. We show that in mouse visual cortex, models with shared noise across brain regions out-perform models with independent per-region noise.

Methods based on sparse representation have achieved success in human activity recognition. However, these methods, either emphasize too much on the sparsity but neglect the correlation in the activity training set, or underline the correlation but ignore the discriminative ability of the sparsity. Besides, the recognition speed of these methods is not fast enough. This paper proposes a fast and adaptive sparse representation classification method for human activity recognition, taking both correlation and sparsity into consideration. Random projection is first used to reduce the dimensionality of the activity signals. And then a simplified near neighbor algorithm is proposed to quickly and optimally reduce the training set. Next, the class of the test sample is determined by solving an adaptively joint L1-norm and L2-norm minimization problem using our pro-posed Alternating Direction Optimization Method. The effectiveness of our method is finally validated on an open Wearable Action Recognition Database. Results demonstrate that our method beats the traditional sparse representation classification method and the conventional near neighbor algorithm in accuracy, and the runtime of our method is also much less than the traditional sparse representation classification method.

We propose an automated algorithm for segmentation of mitochondria from widefield fluorescence microscopy images for quantitative morphology characterization. Mitochondria are membrane-bound organelles that are essential to cells of higher living organisms. Reliable and precise quantitative characterization of their shape is crucial to understanding related physiology and disease mechanisms. Building upon the active-mask framework developed for segmentation of confocal fluorescence microscope images, we propose a new adaptive region-based distributing function to effectively address the problem of halo artifacts that are common in widefield fluorescence images. Such artifacts prevent the segmentation of weak features of mitochondria using existing algorithms. We compare the algorithm to the original active-mask algorithm as well as the geodesic active contour algorithm based on hand-segmented ground truth, and find that it performs significantly better both qualitatively and quantitatively.