Latent space of a small genetic network: Geometry of dynamics and information

Author:

Seyboldt Rabea1,Lavoie Juliette1ORCID,Henry Adrien1ORCID,Vanaret Jules12,Petkova Mariela D.3,Gregor Thomas456,François Paul1ORCID

Affiliation:

1. Physics Department, McGill University, Montreal, QC H3A2T8, Canada

2. Université Lyon, Ecole Normale Supérieure de Lyon, Laboratoire de Physique, UMR 5672, Université Claude Bernard Lyon 1, CNRS, 69342, Lyon, France

3. Program in Biophysics, Harvard University, Cambridge, MA 02138

4. Joseph Henry Laboratory of Physics, Princeton University, Princeton, NJ 08544

5. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544

6. Department of Stem Cell and Developmental Biology, UMR3738, Institut Pasteur, 75015 Paris, France

Abstract

The high-dimensional character of most biological systems presents genuine challenges for modeling and prediction. Here we propose a neural network–based approach for dimensionality reduction and analysis of biological gene expression data, using, as a case study, a well-known genetic network in the early Drosophila embryo, the gap gene patterning system. We build an autoencoder compressing the dynamics of spatial gap gene expression into a two-dimensional (2D) latent map. The resulting 2D dynamics suggests an almost linear model, with a small bare set of essential interactions. Maternally defined spatial modes control gap genes positioning, without the classically assumed intricate set of repressive gap gene interactions. This, surprisingly, predicts minimal changes of neighboring gap domains when knocking out gap genes, consistent with previous observations. Latent space geometries in maternal mutants are also consistent with the existence of such spatial modes. Finally, we show how positional information is well defined and interpretable as a polar angle in latent space. Our work illustrates how optimization of small neural networks on medium-sized biological datasets is sufficiently informative to capture essential underlying mechanisms of network function.

Funder

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

National Science Foundation

HHS | National Institutes of Health

Simons Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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