相关论文: Modeling Gene Expression Distributional Shifts for…
Cellular response to a perturbation is the result of a dynamic system of biological variables linked in a complex network. A major challenge in drug and disease studies is identifying the key factors of a biological network that are…
We consider the problem of predicting perturbation effects via causal models. In many applications, it is a priori unknown which mechanisms of a system are modified by an external perturbation, even though the features of the perturbation…
Feedback in cellular processes is typically inferred through cellular responses to experimental perturbations. Modular response analysis provides a theoretical framework for translating specific perturbations into feedback sensitivities…
Observation of phenotypic diversity in a population of genetically identical cells is often linked to the stochastic nature of chemical reactions involved in gene regulatory networks. We investigate the distribution of population averaged…
Stochasticity in gene expression can result in fluctuations in gene product levels. Recent experiments indicated that feedback regulation plays an important role in controlling the noise in gene expression. A quantitative understanding of…
Predicting the responses of a cell under perturbations may bring important benefits to drug discovery and personalized therapeutics. In this work, we propose a novel graph variational Bayesian causal inference framework to predict a cell's…
Understanding how small molecules perturb gene expression is essential for uncovering drug mechanisms, predicting off-target effects, and identifying repurposing opportunities. While prior deep learning frameworks have integrated multimodal…
Biological structure and function depend on complex regulatory interactions between many genes. A wealth of gene expression data is available from high-throughput genome-wide measurement technologies, but effective gene regulatory network…
We consider the problem of modeling the effects of perturbations like gene knockouts on measurements such as single-cell RNA counts. Given data for some perturbations, we aim to predict the distribution of measurements for new combinations…
Fluctuations in the measured mRNA levels of unperturbed cells under fixed conditions have often been viewed as an impediment to the extraction of information from expression profiles. Here, we argue that such expression fluctuations should…
Next-generation sequencing technologies now constitute a method of choice to measure gene expression. Data to analyze are read counts, commonly modeled using Negative Binomial distributions. A relevant issue associated with this…
We present a new experimental-computational technology of inferring network models that predict the response of cells to perturbations and that may be useful in the design of combinatorial therapy against cancer. The experiments are…
Gene expression is significantly stochastic making modeling of genetic networks challenging. We present an approximation that allows the calculation of not only the mean and variance but also the distribution of protein numbers. We assume…
Metabolic heterogeneity is widely recognised as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular…
We propose a probabilistic model for interpreting gene expression levels that are observed through single-cell RNA sequencing. In the model, each cell has a low-dimensional latent representation. Additional latent variables account for…
Signal-processing molecules inside cells are often present at low copy number, which necessitates probabilistic models to account for intrinsic noise. Probability distributions have traditionally been found using simulation-based approaches…
Gene expression in individual cells is highly variable and sporadic, often resulting in the synthesis of mRNAs and proteins in bursts. Bursting in gene expression is known to impact cell-fate in diverse systems ranging from latency in HIV-1…
In tumoral cells, gene regulation mechanisms are severely altered, and these modifications in the regulations may be characteristic of different subtypes of cancer. However, these alterations do not necessarily induce differential…
Gene regulation involves a hierarchy of events that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. The effects of DNA sequence on these processes have typically been studied based…
Gene expression-based heterogeneity analysis has been extensively conducted. In recent studies, it has been shown that network-based analysis, which takes a system perspective and accommodates the interconnections among genes, can be more…