SP-printer: reconstruction of tumor stage-specific microenvironments via phenotype-integrated spatial...

Area of Science:

• Oncology
• Genomics
• Bioinformatics

Background:

• Spatial transcriptomics (ST) enables high-resolution mRNA mapping within the tumor microenvironment (TME).
• Current ST methods often neglect crucial phenotypic information like malignancy status.
• This limits the comprehensive interpretation of TME mechanisms.

Purpose of the Study:

• To introduce SP-printer, a novel approach for integrating spatial and phenotypic data.
• To quantify stage-specific malignancy levels within the TME at a spot resolution.
• To enhance the interpretability and precision of ST analyses.

Main Methods:

• SP-printer utilizes a S-score strategy to identify stage-specific metagenes from bulk RNA-seq data.
• Metagenes are mapped to ST data at the pixel level using an information-enhanced strategy.
• Pixel-level mappings are aggregated to spot resolution for compatibility with standard ST workflows.

Main Results:

• SP-printer demonstrates superior performance in identifying malignant regions across various tumor types.
• Early diagnostic markers for primary liver cancer and liver metastasis were identified.
• The effects of seven drugs on the TME were evaluated, assessing therapeutic potential.

Conclusions:

• SP-printer provides a unified framework for dissecting the spatial TME.
• It bridges the gap between cellular context and phenotypic outcomes.
• This enhances TME analysis precision and supports informed clinical decision-making.