Related papers: Interpretable Modeling of Single-cell perturbation…
Phenotypic drug discovery has attracted widespread attention because of its potential to identify bioactive molecules. Transcriptomic profiling provides a comprehensive reflection of phenotypic changes in cellular responses to external…
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…
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…
Learning robust representations to discriminate cell phenotypes based on microscopy images is important for drug discovery. Drug development efforts typically analyse thousands of cell images to screen for potential treatments. Early works…
Predicting drug response in patients from preclinical data remains a major challenge in precision oncology due to the substantial biological gap between in vitro cell lines and patient tumors. Rather than aiming to improve absolute in vitro…
Predicting transcriptional responses to novel drugs provides a unique opportunity to accelerate biomedical research and advance drug discovery efforts. However, the inherent complexity and high dimensionality of cellular responses, combined…
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…
Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains…
This paper introduces the Single-Cell Perturbation Prediction Diffusion Model (scPPDM), the first diffusion-based framework for single-cell drug-response prediction from scRNA-seq data. scPPDM couples two condition channels,…
Single-cell data provide high-dimensional measurements of the transcriptional states of cells, but extracting insights into the regulatory functions of genes, particularly identifying transcriptional mechanisms affected by biological…
Microscopy-based phenotypic profiling is scalable for drug discovery but lacks the mechanistic depth of transcriptomics, which remains costly and scarce. Existing multimodal approaches either use images to support other modalities or…
Understanding the relationships among genes, compounds, and their interactions in living organisms remains limited due to technological constraints and the complexity of biological data. Deep learning has shown promise in exploring these…
We present a systematic evaluation framework - thirty-seven analyses, 153 statistical tests, four cell types, two perturbation modalities - for assessing mechanistic interpretability in single-cell foundation models. Applying this framework…
Estimating single-cell responses across various perturbations facilitates the identification of key genes and enhances drug screening, significantly boosting experimental efficiency. However, single-cell sequencing is a destructive process,…
When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize…
A central goal in systems biology and drug discovery is to predict the transcriptional response of cells to perturbations. This task is challenging due to the noisy and sparse nature of single-cell measurements, as well as the fact that…
We train a neural network to predict distributional responses in gene expression following genetic perturbations. This is an essential task in early-stage drug discovery, where such responses can offer insights into gene function and inform…
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…
Without any means of interpretation, neural networks that predict molecular properties and bioactivities are merely black boxes. We will unravel these black boxes and will demonstrate approaches to understand the learned representations…
Predicting the effects of chemical and genetic perturbations on quantitative cell states is a central challenge in computational biology, molecular medicine and drug discovery. Recent work has leveraged large-scale single-cell data and…