Statistical Methods for Spatial Biology
Statistical Methods for Spatial Biology
We are an interdisciplinary team at the University of Michigan, developing innovative spatial analysis methods and software tools for spatial multiplex imaging, digital histopathology, and spatial transcriptomics.
Our goal is to elucidate the mechanisms underlying oncogenesis and the interactions between cells within the spatial context of the tumor microenvironment. By understanding these dynamics, we aim to advance the collective knowledge of cancer mechanisms and guide the development of innovative therapeutic strategies that improve clinical outcomes.
Please check out our recent review paper in this area.
Research Topics
Our research utilizes cutting-edge multiplex imaging to explore the complex interactions within the tumor microenvironment (TME). We employ state-of-the-art multiplex imaging technologies to simultaneously detect multiple biomarkers, enabling precise mapping of the spatial and functional relationships among diverse cellular populations.
In addition to using tissue segmentation, signal quantification, and cell phenotyping, we focus on developing specialized methods to study cellular interactions. These techniques are crucial for understanding the complex dynamics between tumor cells, immune cells, and the extracellular matrix.
A better understanding of cellular interactions within TME can aid in developing predictive models for treatment response and identifying novel targets for cancer therapy.
Our research focuses on the quantitative analysis of cancer digital histopathology. We utilize high-resolution images of tissue samples, mainly Hematoxylin and Eosin (H&E) stained images, to perform detailed assessments of the tumor microenvironment (TME).
The analysis involves preprocessing techniques such as semantic, patch, or cell segmentation to prepare images for advanced statistical modeling.
By employing sophisticated statistical models, we explore the complex interplay between different cellular components within the TME. This includes assessing interactions between tumor cells and other cellular entities, which are crucial for understanding disease progression and treatment responses.
Our goal is to harness these insights to predict patient outcomes more accurately and to identify potential therapeutic targets in oncology.
Our research focuses on spatial transcriptomics, an advanced technique that combines gene expression profiling with spatial information. This method allows us to observe where specific genes are expressed within the context of tissue architecture.
Utilizing this technology, we develop methods and analytic tools to gain a gene-level understanding of cellular organization, interactions, and functions within cancer tissues.
It enables the identification of novel therapeutic targets and the development of more precise diagnostic and treatment strategies by preserving the spatial context of gene activity.
Research Projects
DIMPLE: an R package to quantify, visualize, and model spatial cellular interactions from multiplex imaging with distance matrices
This paper introduces DIMPLE, a scalable analytical framework and accompanying R package designed to quantify, visualize, and model cell-cell interactions in the tumor microenvironment (TME) using advanced multiplexed imaging technologies. By applying DIMPLE to publicly available MI data, we identify statistically significant associations between image-level measures of cell-cell interactions and patient-level covariates, highlighting the potential of this tool to enhance our understanding of tumor biology.
Paper: https://doi.org/10.1016/j.patter.2023.100879
Github/R Package: https://github.com/nateosher/dimple
Shiny App: https://bayesrx.shinyapps.io/DIMPLE_Shiny
SPARTIN: a Bayesian method for the quantification and characterization of cell type interactions in spatial pathology data
This paper presents SPARTIN, a Bayesian method for spatially quantifying immune cell infiltration in high-resolution digital pathology images, introducing the Cell Type Interaction Probability (CTIP) to measure tumor-immune interactions. Using SPARTIN to analyze 335 melanoma biopsies, the study reveals significant associations between CTIP scores and immune cell prevalence as well as genomic and clinical outcomes. The findings highlight SPARTIN's potential to enhance understanding of spatial cellular interactions and their implications for treatment and prognosis in skin cutaneous melanoma.
Paper: https://doi.org/10.3389/fgene.2023.1175603
Github/R Package: https://github.com/bayesrx/SPARTIN
Data Visualization Platform: https://nateosher.github.io/SPARTIN-vis.html
This paper presents SpaceX, a Bayesian methodology designed to identify shared and cluster-specific gene co-expression networks in spatially resolved transcriptomics data. By employing an over-dispersed spatial Poisson model and a high-dimensional factor model, SpaceX enhances the detection of co-expression patterns while accounting for spatial correlations and noise. Analysis of datasets from mouse hypothalamus and human breast cancer reveals multiple hub genes associated with cognitive functions and tumor biology.
Paper: https://doi.org/10.1093/bioinformatics/btac645
Github/R Package: https://github.com/bayesrx/SpaceX
GraphR: probabilistic graphical modeling under heterogeneity
This paper introduces GraphR, a Bayesian framework for incorporating sample heterogeneity in probabilistic graphical models to study complex biological networks in multi-omics data. GraphR utilizes a regression-based formulation to capture sample-specific network structures and variational Bayes for computational efficiency, enabling sparse, scalable, and interpretable network estimation. Applied to diverse multi-omics and spatial transcriptomics datasets, GraphR identifies network features associated with intra- and inter-sample variability, uncovering biological insights that are challenging for traditional homogeneous models.
Paper: https://doi.org/10.1101/2023.10.13.562136
Github/R Package: https://github.com/bayesrx/GraphR
Shiny App: https://bayesrx.shinyapps.io/GraphR