arXiv subjects

Sisi Chen

Publications and source records attributed to Sisi Chen.

3 recordsLinked to original sources

arXiv2025

A Model Intercomparison Study of Mixed-Phase Clouds in a Laboratory Chamber

Mixed-phase clouds, composed of supercooled liquid droplets and ice crystals, play a critical role in weather and climate systems. Their complex microphysical interactions and coupling with turbulence at microscales govern the cloud properties at macroscales, yet remain challenging to observe and quantify under atmospheric conditions. This model intercomparison study utilizes ten model configurations to simulate mixed-phase cloud evolution in the Michigan Technological University's Pi Chamber. The models span a range of frameworks, including box models, direct numerical simulation, and large-eddy simulation models, and incorporate both bin and Lagrangian microphysics. Each model was tuned to reproduce the observed liquid-phase steady state prior to ice injection. Ice particles were then introduced into the domain at various rates to examine cloud glaciation behavior. By the intercomparison design, all models successfully reproduced the observed mean droplet radius and number concentration during the liquid-phase stage. Increasing ice particle injection rates led to consistent qualitative trends across models: depletion of liquid water, reduced total water content, and a shift in particle size distributions toward larger radii. However, quantitative differences arose due to variations in model treatment in dynamics and microphysics, including subgrid-scale turbulence parameterizations, wall forcing, and particle removal parameterizations. Most models that simulate the full chamber retained liquid droplets near the lower boundary, where supersaturation forcing is strongest and droplets are replenished before mixing into the core region. These surviving liquids droplets were absent in simulations assuming a well-mixed domain, excluding the near-wall region, or using coarse grid spacing.

physics.ao-ph↗

arXiv2022

Therapeutic algebra of immunomodulatory drug responses at single-cell resolution

Therapeutic modulation of immune states is central to the treatment of human disease. However, how drugs and drug combinations impact the diverse cell types in the human immune system remains poorly understood at the transcriptome scale. Here, we apply single-cell mRNA-seq to profile the response of human immune cells to 502 immunomodulatory drugs alone and in combination. We develop a unified mathematical model that quantitatively describes the transcriptome scale response of myeloid and lymphoid cell types to individual drugs and drug combinations through a single inferred regulatory network. The mathematical model reveals how drug combinations generate novel, macrophage and T-cell states by recruiting combinations of gene expression programs through both additive and non-additive drug interactions. A simplified drug response algebra allows us to predict the continuous modulation of immune cell populations between activated, resting and hyper-inhibited states through combinatorial drug dose titrations. Our results suggest that transcriptome-scale mathematical models could enable the design of therapeutic strategies for programming the human immune system using combinations of therapeutics.

q-bio.GN↗

arXiv2022

Active feature selection discovers minimal gene sets for classifying cell types and disease states with single-cell mRNA-seq data

Sequencing costs currently prohibit the application of single-cell mRNA-seq to many biological and clinical analyses. Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here, we introduce an active learning method (ActiveSVM) that identifies minimal but highly-informative gene sets that enable the identification of cell-types, physiological states, and genetic perturbations in single-cell data using a small number of genes. Our active feature selection procedure generates minimal gene sets from single-cell data through an iterative cell-type classification task where misclassified cells are examined at each round of analysis to identify maximally informative genes through an `active' support vector machine (ActiveSVM) classifier. By focusing computational resources on misclassified cells, ActiveSVM scales to analyze data sets with over a million single cells. We demonstrate that ActiveSVM feature selection identifies gene sets that enable ~90% cell-type classification accuracy across a variety of data sets including cell atlas and disease characterization data sets. The method generalizes to reveal genes that respond to genetic perturbations and to identify region specific gene expression patterns in spatial transcriptomics data. The discovery of small but highly informative gene sets should enable substantial reductions in the number of measurements necessary for application of single-cell mRNA-seq to clinical tests, therapeutic discovery, and genetic screens.

q-bio.GN↗