FEAST

Simulation and interpolation of spatial transcriptomics from parameter cloud

FEAST: Simulation and interpolation of spatial transcriptomics from parameter cloud

Status: Independent first-author project; manuscript in final preparation

Role: First author, Independent Research Project

Institution: ZJU-UoE Institute, Zhejiang University; collaboration with Prof. Maizie Zhou Lab, Vanderbilt University

Duration: August 2024 – Present (Remote and on-site collaboration)

Preprint PDF

Project Overview

FEAST (FEAture-space based modeling for Spatial Transcriptomics) is an independent first-author project on parameter-cloud modeling for spatial transcriptomics. The framework represents gene-level mean, variance, and sparsity in a latent parameter space, then uses that structure to simulate realistic slices and interpolate tissue states across space.

Beyond two dimensions, FEAST extends to 3D interpolation through optimal-transport-guided transitions between parameter clouds, supporting volumetric reconstruction and systematic benchmarking for spatial omics methods.

Code: GitHub · PyPI

Technical Innovation

Statistical Modeling:

  • Parameter-cloud representation: models gene-level mean, variance, and sparsity in a unified latent space
  • C-vine copula modeling: captures nonlinear and asymmetric dependence among gene parameters
  • Flexible count models: supports Poisson, Negative Binomial, ZIP, and ZINB distributions

Simulation Framework:

  • Single-slice simulation: generates realistic 2D spatial transcriptomics slices with controllable perturbations
  • Expression alteration: tunes mean, variance, and sparsity for robustness testing
  • Spatial transformation: enables geometry-aware benchmarking for alignment methods

3D Interpolation:

  • Optimal transport: Wasserstein-style interpolation between parameter clouds
  • Alignment-guided coordinates: transport-informed coordinate interpolation
  • Volumetric reconstruction: generates intermediate slices for continuous 3D tissue architectures

Key Results

  • High-fidelity simulation with near-perfect correlation for gene means and variances across multiple ST platforms (10x Visium, MERFISH, OpenST, Slide-seqV2, Xenium, Stereo-seq)
  • Clustering benchmarking revealed algorithmic sensitivities under controlled expression and sparsity perturbations
  • Alignment evaluation demonstrated Spateo’s robustness over SPACEL under geometric transformations
  • 3D interpolation achieved >0.9 correlation with ground-truth experimental slices in leave-one-out validation

Research Scope

This project has involved the full cycle of independent method development:

  • literature review and problem formulation
  • model construction and implementation
  • benchmarking and application studies
  • manuscript preparation and figure development

Current Positioning

FEAST is the clearest expression of my independent research direction so far: building mathematically grounded computational frameworks for simulation, benchmarking, and representation of spatial biological data.