Hidden Markov random field models for cell-type assignment of spatially resolved transcriptomics

Author:

Zhong Cheng1,Tian Tian2,Wei Zhi1ORCID

Affiliation:

1. Department of Computer Science, Ying Wu College of Computing, New Jersey Institute of Technology , Newark, NJ 07102, United States

2. Center for Applied Genomics, Children’s Hospital of Philadelphia , Philadelphia, PA 19104, United States

Abstract

Abstract Motivation The recent development of spatially resolved transcriptomics (SRT) technologies has facilitated research on gene expression in the spatial context. Annotating cell types is one crucial step for downstream analysis. However, many existing algorithms use an unsupervised strategy to assign cell types for SRT data. They first conduct clustering analysis and then aggregate cluster-level expression based on the clustering results. This workflow fails to leverage the marker gene information efficiently. On the other hand, other cell annotation methods designed for single-cell RNA-seq data utilize the cell-type marker genes information but fail to use spatial information in SRT data. Results We introduce a statistical spatial transcriptomics cell assignment model, SPAN, to annotate clusters of cells or spots into known types in SRT data with prior knowledge of predefined marker genes and spatial information. The SPAN model annotates cells or spots from SRT data using predefined overexpressed marker genes and combines a mixture model with a hidden Markov random field to model the spatial dependency between neighboring spots. We demonstrate the effectiveness of SPAN against spatial and nonspatial clustering algorithms through extensive simulation and real data experiments. Availability and implementation https://github.com/ChengZ352/SPAN.

Funder

National Institutes of Health

National Center for Advancing Translational Sciences

National Science Foundation

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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