We introduce an additive Gaussian process (GP) framework accounting for monotonicity constraints and scalable to high dimensions. Our contributions are threefold. First, we show that our framework enables to satisfy the constraints everywhere in the input space. We also show that more general componentwise linear inequality constraints can be handled similarly, such as componentwise convexity. Second, we propose the additive MaxMod algorithm for sequential dimension reduction. By sequentially maximizing a squared-norm criterion, MaxMod identifies the active input dimensions and refines the most important ones. This criterion can be computed explicitly at a linear cost. Finally, we provide open-source codes for our full framework. We demonstrate the performance and scalability of the methodology in several synthetic examples with hundreds of dimensions under monotonicity constraints as well as on a real-world flood application.

The regulatory process of Drosophila is thoroughly studied for understanding a great variety of biological principles. While pattern-forming gene networks are analysed in the transcription step, post-transcriptional events (e.g. translation, protein processing) play an important role in establishing protein expression patterns and levels. Since the post-transcriptional regulation of Drosophila depends on spatiotemporal interactions between mRNAs and gap proteins, proper physically-inspired stochastic models are required to study the link between both quantities. Previous research attempts have shown that using Gaussian processes (GPs) and differential equations lead to promising predictions when analysing regulatory networks. Here we aim at further investigating two types of physically-inspired GP models based on a reaction-diffusion equation where the main difference lies in where the prior is placed. While one of them has been studied previously using protein data only, the other is novel and yields a simple approach requiring only the differentiation of kernel functions. In contrast to other stochastic frameworks, discretising the spatial space is not required here. Both GP models are tested under different conditions depending on the availability of gap gene mRNA expression data. Finally, their performances are assessed on a high-resolution dataset describing the blastoderm stage of the early embryo of Drosophila melanogaster

Gaussian process (GP) modulated Cox processes are widely used to model point patterns. Existing approaches require a mapping (link function) between the unconstrained GP and the positive intensity function. This commonly yields solutions that do not have a closed form or that are restricted to specific covariance functions. We introduce a novel finite approximation of GP-modulated Cox processes where positiveness conditions can be imposed directly on the GP, with no restrictions on the covariance function. Our approach can also ensure other types of inequality constraints (e.g. monotonicity, convexity), resulting in more versatile models that can be used for other classes of point processes (e.g. renewal processes). We demonstrate on both synthetic and real-world data that our framework accurately infers the intensity functions. Where monotonicity is a feature of the process, our ability to include this in the inference improves results.

To survive environmental conditions, cells transcribe their response activities into encoded mRNA sequences in order to produce certain amounts of protein concentrations. The external conditions are mapped into the cell through the activation of special proteins called transcription factors (TFs). Due to the difficult task to measure experimentally TF behaviors, and the challenges to capture their quick-time dynamics, different types of models based on differential equations have been proposed. However, those approaches usually incur in costly procedures, and they present problems to describe sudden changes in TF regulators. In this paper, we present a switched dynamical latent force model for reverse-engineering transcriptional regulation in gene expression data which allows the exact inference over latent TF activities driving some observed gene expressions through a linear differential equation. To deal with discontinuities in the dynamics, we introduce an approach that switches between different TF activities and different dynamical systems. This creates a versatile representation of transcription networks that can capture discrete changes and non-linearities. We evaluate our model on both simulated data and real data (e.g., microaerobic shift in E. coli, yeast respiration), concluding that our framework allows for the fitting of the expression data while being able to infer continuous-time TF profiles.