Chern, K. | bioRxiv Science

bioRxiv2022

SpatialSort: A Bayesian Model for Clustering and CellPopulation Annotation of Spatial Proteomics Data

Emerging spatial proteomics technologies have created new opportunities to move beyond quantifying the composition of cell types in tissue and begin probing spatial structure. However, current methods for analysing such data are designed for non-spatial data and ignore spatial information. We present SpatialSort, a spatially aware Bayesian clustering approach that allows for the incorporation of prior biological knowledge. SpatialSort clusters cells by accounting for affinities of cells of different types to neighbours in space. Additionally, by incorporating prior information about cell types, SpatialSort outperforms current methods and can perform automated annotation of clusters.

bioinformatics↗

bioRxiv2020

Efficient Bayesian inference of phylogenetic trees from large scale, low-depth genome-wide single-cell data

A new generation of scalable single cell whole genome sequencing (scWGS) methods allows unprecedented high resolution measurement of the evolutionary dynamics of cancer cell populations. Phylogenetic reconstruction is central to identifying sub-populations and distinguishing the mutational processes that gave rise to them. Existing phylogenetic tree building models do not scale to the tens of thousands of high resolution genomes achievable with current scWGS methods. We constructed a phylogenetic model and associated Bayesian inference procedure, sitka, specifically for scWGS data. The method is based on a novel phylogenetic encoding of copy number (CN) data, the sitka transformation, that simplifies the site dependencies induced by rearrangements while still forming a sound foundation to phylogenetic inference. The sitka transformation allows us to design novel scalable Markov chain Monte Carlo (MCMC) algorithms. Moreover, we introduce a novel point mutation calling method that incorporates the CN data and the underlying phylogenetic tree to overcome the low per-cell coverage of scWGS. We demonstrate our method on three single cell datasets, including a novel PDX series, and analyse the topological properties of the inferred trees. Sitka is freely available at https://github.com/UBC-Stat-ML/sitkatree.git.

bioinformatics↗