Deconfounded Dimension Reduction via Partial Embeddings.

Dimension reduction tools preserving similarity and graph structure such as t-SNE and UMAP can capture complex biological patterns in high-dimensional data. However, these tools typically are not designed to separate effects of interest from unwanted effects due to confounders. We introduce the partial embedding (PARE) framework, which enables removal of confounders from any distance-based dimension reduction method. We then develop partial t-SNE and partial UMAP and apply these methods to genomic and neuroimaging data. Our results show that the PARE framework can remove batch effects in single-cell sequencing data as well as separate clinical and technical variability in neuroimaging measures. We demonstrate that the PARE framework extends dimension reduction methods to highlight biological patterns of interest while effectively removing confounding effects.

MIMoSA: An Automated Method for Intermodal Segmentation Analysis of Multiple Sclerosis Brain Lesions.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) is crucial for in vivo detection and characterization of white matter lesions (WMLs) in multiple sclerosis. While WMLs have been studied for over two decades using MRI, automated segmentation remains challenging. Although the majority of statistical techniques for the automated segmentation of WMLs are based on single imaging modalities, recent advances have used multimodal techniques for identifying WMLs. Complementary modalities emphasize different tissue properties, which help identify interrelated features of lesions. METHODS: Method for Inter-Modal Segmentation Analysis (MIMoSA), a fully automatic lesion segmentation algorithm that utilizes novel covariance features from intermodal coupling regression in addition to mean structure to model the probability lesion is contained in each voxel, is proposed. MIMoSA was validated by comparison with both expert manual and other automated segmentation methods in two datasets. The first included 98 subjects imaged at Johns Hopkins Hospital in which bootstrap cross-validation was used to compare the performance of MIMoSA against OASIS and LesionTOADS, two popular automatic segmentation approaches. For a secondary validation, a publicly available data from a segmentation challenge were used for performance benchmarking. RESULTS: In the Johns Hopkins study, MIMoSA yielded average Sørensen-Dice coefficient (DSC) of .57 and partial AUC of .68 calculated with false positive rates up to 1%. This was superior to performance using OASIS and LesionTOADS. The proposed method also performed competitively in the segmentation challenge dataset. CONCLUSION: MIMoSA resulted in statistically significant improvements in lesion segmentation performance compared with LesionTOADS and OASIS, and performed competitively in an additional validation study.