Removing Inter-Experimental Variability from Functional Data in Systems Neuroscience

Dominic Gonschorek, Larissa Höfling, Klaudia P. Szatko, Katrin Franke, Timm Schubert, Benjamin Adric Dunn, Philipp Berens, David A. Klindt, Thomas Euler

Keywords: systems neuroscience, inter-experimental variability, cell type classification, retina, domain adaptation, autoencoder, adversarial optimization

TL;DR: We offer a flexible approach to remove inter-experimental variability and integrate datasets across experiments in systems neuroscience.

Abstract: Integrating data from multiple experiments is common practice in systems neuroscience but it requires inter-experimental variability to be negligible compared to the biological signal of interest. This requirement is rarely fulfilled; systematic changes between experiments can drastically affect the outcome of complex analysis pipelines. Modern machine learning approaches designed to adapt models across multiple data domains offer flexible ways of removing inter-experimental variability where classical statistical methods often fail. While applications of these methods have been mostly limited to single-cell genomics, in this work, we develop a theoretical framework for domain adaptation in systems neuroscience. We implement this in an adversarial optimization scheme that removes inter-experimental variability while preserving the biological signal. We compare our method to previous approaches on a large-scale dataset of two-photon imaging recordings of retinal bipolar cell responses to visual stimuli. This dataset provides a unique benchmark as it contains biological signal from well-defined cell types that is obscured by large inter-experimental variability. In a supervised setting, we compare the generalization performance of cell type classifiers across experiments, which we validate with anatomical cell type distributions from electron microscopy data. In an unsupervised setting, we remove inter-experimental variability from the data which can then be fed into arbitrary downstream analyses. In both settings, we find that our method achieves the best trade-off between removing inter-experimental variability and preserving biological signal. Thus, we offer a flexible approach to remove inter-experimental variability and integrate datasets across experiments in systems neuroscience. Code available at https://github.com/eulerlab/rave.

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Code: https://github.com/eulerlab/rave