Abstract Nonnegative matrix factorization (NMF) is widely used to analyze high-dimensional count data because, in contrast to real-valued alternatives such as factor analysis, it produces an interpretable parts-based representation. However, in applications such as spatial transcriptomics, NMF fails to incorporate known structure between observations. Here, we present nonnegative spatial factorization (NSF), a spatially-aware probabilistic dimension reduction model based on transformed Gaussian processes that naturally encourages sparsity and scales to tens of thousands of observations. NSF recovers ground truth factors more accurately than real-valued alternatives such as MEFISTO in simulations, and has lower out-of-sample prediction error than probabilistic NMF on three spatial transcriptomics datasets from mouse brain and liver. Since not all patterns of gene expression have spatial correlations, we also propose a hybrid extension of NSF that combines spatial and nonspatial components, enabling quantification of spatial importance for both observations and features. A TensorFlow implementation of NSF is available fromhttps://github.com/willtownes/nsf-paper.
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Hybrid Clustering of Single-Cell Gene Expression and Spatial Information via Integrated NMF and K-Means
Advances in single cell transcriptomics have allowed us to study the identity of single cells. This has led to the discovery of new cell types and high resolution tissue maps of them. Technologies that measure multiple modalities of such data add more detail, but they also complicate data integration. We offer an integrated analysis of the spatial location and gene expression profiles of cells to determine their identity. We propose scHybridNMF (single-cell Hybrid Nonnegative Matrix Factorization), which performs cell type identification by combining sparse nonnegative matrix factorization (sparse NMF) with k-means clustering to cluster high-dimensional gene expression and low-dimensional location data. We show that, under multiple scenarios, including the cases where there is a small number of genes profiled and the location data is noisy, scHybridNMF outperforms sparse NMF, k-means, and an existing method that uses a hidden Markov random field to encode cell location and gene expression data for cell type identification.
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- Award ID(s):
- 2019771
- PAR ID:
- 10319835
- Date Published:
- Journal Name:
- Frontiers in Genetics
- Volume:
- 12
- ISSN:
- 1664-8021
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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