Gene Expression Prediction and Smoothing from Whole Slide Histopathology Images

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Abstract: Recent advances in Spatial Transcriptomics (ST) pair histology images with spatially resolved gene expression profiles, enabling predictions of gene expression across different tissue locations based on image patches. This opens up new possibilities for enhancing whole slide image (WSI) prediction tasks with localized gene expression. However, existing methods do not fully leverage the interactions between different tissue locations, which are crucial for accurate joint prediction. To address this, we introduce MERGE (Multi-faceted hiErarchical gRaph for Gene Expressions), which combines a multi-faceted hierarchical graph construction strategy with graph neural networks (GNN) to improve gene expression predictions from WSIs. By clustering tissue image patches based on both spatial and morphological features, and incorporating intra- and inter-cluster edges, our approach fosters interactions between distant tissue locations during GNN learning. As an additional contribution, we evaluate different data smoothing techniques that are necessary to mitigate artifacts in ST data, often caused by technical imperfections. We advocate for adopting gene-aware smoothing methods that are more biologically justified. Experimental results on gene expression prediction show that our GNN method outperforms state-of-the-art techniques on multiple metrics such as mean squared error (MSE), mean absolute error (MAE), and pearson correlation coefficient (PCC). Qualitative analysis establishes the effectiveness of MERGE in capturing cancer marker genes, thus consolidating its utility in diagnostics. As an extension of this work, we use MERGE in a setting with an uncertainty calibration branch to perform robust gene expression smoothing. We show that using patch-wise uncertainty from an uncertainty calibration model and the gene expression predictions from MERGE to enrich the ground truth gene expression matrix, results in better alignment with pathologist annotations, thus establishing that the smoothing is biologically informed.

Speaker: Aniruddha Ganguly

Location: Virtual Zoom Meeting


https://stonybrook.zoom.us/j/5474847973?pwd=Sng0Q2h1c1d3cm9sbFBmYUczMHZNdz09
Meeting ID: 547 484 7973
Passcode: 206739

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