De Moor, B. | Search bioRxiv

bioRxiv2020

Correspondence-aware manifold learning for microscopic and spatial omics imaging: a novel data fusion method bringing MSI to a cellular resolution.

High-dimensional molecular measurements are transforming the field of pathology into a data-driven discipline. While H&E stainings are still the gold standard to diagnose disease, the integration of microscopic and molecular information is becoming crucial to advance our understanding of tissue heterogeneity. To this end, we propose a data fusion method that integrates spatial omics and microscopic data obtained from the same tissue slide. Through correspondence-aware manifold learning, we can visualise the biological trends observed in the high-dimensional omics data at microscopic resolution. While data fusion enables the detection of elements that would not be detected taking into account the separate data modalities individually, out-of-sample prediction makes it possible to predict molecular trends outside of the measured tissue area. The proposed dimensionality reduction-based data fusion paradigm will therefore be helpful in deciphering molecular heterogeneity by bringing molecular measurements such as MSI to the cellular resolution.

bioinformatics↗

bioRxiv2020

Spatially-Aware Clustering of Ion Images in Mass Spectrometry Imaging Data Using Deep Learning

Computational analysis is crucial to capitalize on the wealth of spatio-molecular information generated by mass spectrometry imaging (MSI) experiments. Currently, the spatial information available in MSI data is often under-utilized, due to the challenges of in-depth spatial pattern extraction. The advent of deep learning has greatly facilitated such complex spatial analysis. In this work, we use a pre-trained neural network to extract high-level features from ion images in MSI data, and test whether this improves downstream data analysis. The resulting neural network interpretation of ion images, coined neural ion images, are used to cluster ion images based on spatial expressions. We evaluate the impact of neural ion images on two ion image clustering pipelines, namely DBSCAN clustering, combined with UMAP-based dimensionality reduction, and k-means clustering. In both pipelines, we compare regular and neural ion images from two different MSI datasets. All tested pipelines could extract underlying spatial patterns, but the neural network-based pipelines provided better assignment of ion images, with more fine-grained clusters, and greater consistency in the spatial structures assigned to individual clusters. Additionally, we introduce the Relative Isotope Ratio metric to quantitatively evaluate clustering quality. The resulting scores show that isotopical m/z values are more often clustered together in the neural network-based pipeline, indicating improved clustering outcomes. The usefulness of neural ion images extends beyond clustering towards a generic framework to incorporate spatial information into any MSI-focused machine learning pipeline, both supervised and unsupervised.

bioinformatics↗