CISPA
Browse
v1_covered.pdf (1.19 MB)

Biologically informed NeuralODEs for genome-wide regulatory dynamics

Download (1.19 MB)
preprint
posted on 2024-03-25, 14:01 authored by Intekhab Hossain, Viola Fanfani, John Quackenbush, Rebekka BurkholzRebekka Burkholz
Models that are formulated as ordinary differential equations (ODEs) can accurately explain temporal gene expression patterns and promise to yield new insights into important cellular processes, disease progression, and intervention design. Learning such ODEs is challenging, since we want to predict the evolution of gene expression in a way that accurately encodes the causal gene-regulatory network (GRN) governing the dynamics and the nonlinear functional relationships between genes. Most widely used ODE estimation methods either impose too many parametric restrictions or are not guided by meaningful biological insights, both of which impedes scalability and/or explainability. To overcome these limitations, we developed PHOENIX, a modeling framework based on neural ordinary differential equations (NeuralODEs) and Hill-Langmuir kinetics, that can flexibly incorporate prior domain knowledge and biological constraints to promote sparse, biologically interpretable representations of ODEs. We test accuracy of PHOENIX in a series of in silico experiments benchmarking it against several currently used tools for ODE estimation. We also demonstrate PHOENIX's flexibility by studying oscillating expression data from synchronized yeast cells and assess its scalability by modelling genome-scale breast cancer expression for samples ordered in pseudotime. Finally, we show how the combination of user-defined prior knowledge and functional forms from systems biology allows PHOENIX to encode key properties of the underlying GRN, and subsequently predict expression patterns in a biologically explainable way.

History

Primary Research Area

  • Trustworthy Information Processing

Open Access Type

  • Green

BibTeX

@misc{Hossain:Fanfani:Quackenbush:Burkholz:2023, title = "Biologically informed NeuralODEs for genome-wide regulatory dynamics", author = "Hossain, Intekhab" AND "Fanfani, Viola" AND "Quackenbush, John" AND "Burkholz, Rebekka", year = 2023, month = 3, doi = "10.21203/rs.3.rs-2675584/v1" }