STAMarker: determining spatial domain-specific variable genes with saliency maps in deep learning

Author:

Zhang Chihao12,Dong Kangning12,Aihara Kazuyuki3ORCID,Chen Luonan4567ORCID,Zhang Shihua125ORCID

Affiliation:

1. NCMIS, CEMS, RCSDS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences , Beijing  100190 , China

2. School of Mathematical Sciences, University of Chinese Academy of Sciences , Beijing  100049 , China

3. International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, The University of Tokyo , Tokyo  113-0033 , Japan

4. Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai  200031 , China

5. Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences , Hangzhou  310024 , China

6. School of Life Science and Technology, Shanghai Tech University , Shanghai  201210 , China

7. Guangdong Institute of Intelligence Science and Technology , Hengqin, Zhuhai , Guangdong  519031 , China

Abstract

Abstract Spatial transcriptomics characterizes gene expression profiles while retaining the information of the spatial context, providing an unprecedented opportunity to understand cellular systems. One of the essential tasks in such data analysis is to determine spatially variable genes (SVGs), which demonstrate spatial expression patterns. Existing methods only consider genes individually and fail to model the inter-dependence of genes. To this end, we present an analytic tool STAMarker for robustly determining spatial domain-specific SVGs with saliency maps in deep learning. STAMarker is a three-stage ensemble framework consisting of graph-attention autoencoders, multilayer perceptron (MLP) classifiers, and saliency map computation by the backpropagated gradient. We illustrate the effectiveness of STAMarker and compare it with serveral commonly used competing methods on various spatial transcriptomic data generated by different platforms. STAMarker considers all genes at once and is more robust when the dataset is very sparse. STAMarker could identify spatial domain-specific SVGs for characterizing spatial domains and enable in-depth analysis of the region of interest in the tissue section.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

JST Moonshot R&D Grant

AMED

JSPS KAKENHI

Institute of AI and Beyond at the University of Tokyo

Chinese Academy of Sciences

ey-Area Research and Development of Guangdong Province

CAS Project for Young Scientists in Basic Research

Publisher

Oxford University Press (OUP)

Subject

Genetics

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