SD2: spatially resolved transcriptomics deconvolution through integration of dropout and spatial information

Haoyang Li, Hanmin Li, Juexiao Zhou, Xin Gao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Motivation: Unveiling the heterogeneity in the tissues is crucial to explore cell–cell interactions and cellular targets of human diseases. Spatial transcriptomics (ST) supplies spatial gene expression profile which has revolutionized our biological understanding, but variations in cell-type proportions of each spot with dozens of cells would confound downstream analysis. Therefore, deconvolution of ST has been an indispensable step and a technical challenge toward the higher-resolution panorama of tissues. Results: Here, we propose a novel ST deconvolution method called SD2 integrating spatial information of ST data and embracing an important characteristic, dropout, which is traditionally considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract the dropout-based genes as informative features from ST and scRNA-seq data by fitting a Michaelis–Menten function. After synthesizing pseudo-ST spots by randomly composing cells from scRNA-seq data, auto-encoder is applied to discover low-dimensional and non-linear representation of the real- and pseudo-ST spots. Next, we create a graph containing embedded profiles as nodes, and edges determined by transcriptional similarity and spatial relationship. Given the graph, a graph convolutional neural network is used to predict the cell-type compositions for real-ST spots. We benchmark the performance of SD2 on the simulated seqFISHþ dataset with different resolutions and measurements which show superior performance compared with the state-of-the-art methods. SD2 is further validated on three real-world datasets with different ST technologies and demonstrates the capability to localize cell-type composition accurately with quantitative evidence.

Original languageEnglish (US)
Pages (from-to)4878-4884
Number of pages7
JournalBioinformatics
Volume38
Issue number21
DOIs
StatePublished - Nov 1 2022

Bibliographical note

Funding Information:
This work was supported by the Office of Research Administration (ORA) at King Abdullah University of Science and Technology (KAUST) [BAS/1/1624-01, FCC/1/1976-23-01, URF/1/4077-01-01, URF/1/4098-01-01, REI/1/4216-01-01, REI/1/4437-01-01, REI/1/4473-01-01, URF/1/4352-01-01 and REI/1/ 4742-01-01].

Publisher Copyright:
VC The Author(s) 2022. Published by Oxford University Press.

ASJC Scopus subject areas

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

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