CVAM: CNA Profile Inference of the Spatial Transcriptome Based on the VGAE and HMM.
Biomolecules(2023)
Abstract
Tumors are often polyclonal due to copy number alteration (CNA) events. Through the CNA profile, we can understand the tumor heterogeneity and consistency. CNA information is usually obtained through DNA sequencing. However, many existing studies have shown a positive correlation between the gene expression and gene copy number identified from DNA sequencing. With the development of spatial transcriptome technologies, it is urgent to develop new tools to identify genomic variation from the spatial transcriptome. Therefore, in this study, we developed CVAM, a tool to infer the CNA profile from spatial transcriptome data. Compared with existing tools, CVAM integrates the spatial information with the spot's gene expression information together and the spatial information is indirectly introduced into the CNA inference. By applying CVAM to simulated and real spatial transcriptome data, we found that CVAM performed better in identifying CNA events. In addition, we analyzed the potential co-occurrence and mutual exclusion between CNA events in tumor clusters, which is helpful to analyze the potential interaction between genes in mutation. Last but not least, Ripley's K-function is also applied to CNA multi-distance spatial pattern analysis so that we can figure out the differences of different gene CNA events in spatial distribution, which is helpful for tumor analysis and implementing more effective treatment measures based on spatial characteristics of genes.
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Key words
spatial transcriptome,cna profile inference
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