Yves Bernaerts

Jonas Beck, Michael Deistler, Yves Bernaerts et al.

Simulation-based Bayesian inference (SBI) can be used to estimate the parameters of complex mechanistic models given observed model outputs without requiring access to explicit likelihood evaluations. A prime example for the application of SBI in neuroscience involves estimating the parameters governing the response dynamics of Hodgkin-Huxley (HH) models from electrophysiological measurements, by inferring a posterior over the parameters that is consistent with a set of observations. To this end, many SBI methods employ a set of summary statistics or scientifically interpretable features to estimate a surrogate likelihood or posterior. However, currently, there is no way to identify how much each summary statistic or feature contributes to reducing posterior uncertainty. To address this challenge, one could simply compare the posteriors with and without a given feature included in the inference process. However, for large or nested feature sets, this would necessitate repeatedly estimating the posterior, which is computationally expensive or even prohibitive. Here, we provide a more efficient approach based on the SBI method neural likelihood estimation (NLE): We show that one can marginalize the trained surrogate likelihood post-hoc before inferring the posterior to assess the contribution of a feature. We demonstrate the usefulness of our method by identifying the most important features for inferring parameters of an example HH neuron model. Beyond neuroscience, our method is generally applicable to SBI workflows that rely on data features for inference used in other scientific fields.

Yves Bernaerts, Philipp Berens, Dmitry Kobak

Patch-seq, a recently developed experimental technique, allows neuroscientists to obtain transcriptomic and electrophysiological information from the same neurons. Efficiently analyzing and visualizing such paired multivariate data in order to extract biologically meaningful interpretations has, however, remained a challenge. Here, we use sparse deep neural networks with and without a two-dimensional bottleneck to predict electrophysiological features from the transcriptomic ones using a group lasso penalty, yielding concise and biologically interpretable two-dimensional visualizations. In two large example data sets, this visualization reveals known neural classes and their marker genes without biological prior knowledge. We also demonstrate that our method is applicable to other kinds of multimodal data, such as paired transcriptomic and proteomic measurements provided by CITE-seq.