Automated classification of cellular expression in multiplexed imaging data with Nimbus.

Multiplexed imaging offers a powerful approach to characterize the spatial topography of tissues in both health and disease. To analyze such data, the specific combination of markers that are present in each cell must be enumerated to enable accurate phenotyping, a process that often relies on unsupervised clustering. We constructed the Pan-Multiplex (Pan-M) dataset containing 197 million distinct annotations of marker expression across 15 different cell types. We used Pan-M to create Nimbus, a deep learning model to predict marker positivity from multiplexed image data. Nimbus is a pre-trained model that uses the underlying images to classify marker expression across distinct cell types, from different tissues, acquired using different microscope platforms, without requiring any retraining. We demonstrate that Nimbus predictions capture the underlying staining patterns of the full diversity of markers present in Pan-M. We then show how Nimbus predictions can be integrated with downstream clustering algorithms to robustly identify cell subtypes in image data. We have open-sourced Nimbus and Pan-M to enable community use at https://github.com/angelolab/Nimbus-Inference.

The steady state and response to a periodic stimulation of the firing rate for a theta neuron with correlated noise.

The stochastic activity of neurons is caused by various sources of correlated fluctuations and can be described in terms of simplified, yet biophysically grounded, integrate-and-fire models. One paradigmatic model is the quadratic integrate-and-fire model and its equivalent phase description by the theta neuron. Here we study the theta neuron model driven by a correlated Ornstein-Uhlenbeck noise and by periodic stimuli. We apply the matrix-continued-fraction method to the associated Fokker-Planck equation to develop an efficient numerical scheme to determine the stationary firing rate as well as the stimulus-induced modulation of the instantaneous firing rate. For the stationary case, we identify the conditions under which the firing rate decreases or increases by the effect of the colored noise and compare our results to existing analytical approximations for limit cases. For an additional periodic signal we demonstrate how the linear and nonlinear response terms can be computed and report resonant behavior for some of them. We extend the method to the case of two periodic signals, generally with incommensurable frequencies, and present a particular case for which a strong mixed response to both signals is observed, i.e. where the response to the sum of signals differs significantly from the sum of responses to the single signals. We provide Python code for our computational method: https://github.com/jannikfranzen/theta_neuron .