Identification of spatial expression trends in single-cell gene expression data

As methods for measuring spatial gene expression at single-cell resolution become available, there is a need for computational analysis strategies. Karolinska Institutet researchers present trendsceek, a method based on marked point processes that identifies genes with statistically significant spatial expression trends. trendsceek finds these genes in spatial transcriptomic and sequential fluorescence in situ hybridization data, and also reveals significant gene expression gradients and hot spots in low-dimensional projections of dissociated single-cell RNA-seq data.

Application of trendsceek to spatial and single-cell gene expression data

rna-seq

(a) Spatial transcriptomics data from mouse olfactory bulb (tissue section “replicate 3”; n = 269 array spots). Left, hematoxylin-and-eosin-stained tissue section. Right, examples of genes with significant expression trends in the tissue sample. Expression was scaled to the range of 0–1 by unity-based normalization. (b) Density plots of gene expression in the sample shown in a, with cells in regions of significantly elevated expression colored red. (c,d) Spatial transcriptomics data (c) and density plots (d) from mouse olfactory bulb (tissue section “replicate 12”; n = 280 array spots). (e) Spatial transcriptomics data from breast cancer biopsy (histological section “Layer 2,” n = 251 array spots), with examples of genes with significant expression trends within the tissue sample. (a,c,e) The distance between array spots is 200 μm, and each spot covers multiple cells. (f) Examples of distinct spatial gene expression patterns identified by trendsceek in E6.5 mouse epiblast cells . (g) Identification of spatial patterns related to the positions of male and female cells within the cluster shown in f, with mutually exclusive expression of Xist (expressed in female cells) and Eif2s3y (located on the Y-chromosome and expressed only in male cells). (h) Examples of spatial expression patterns identified in mouse hippocampus seqFISH data (cells imaged in each highlighted region: H, 93; O, 89; T, 208; S, 214). Left, an illustration of hippocampus with labels indicating the 21 regions imaged in a previous study. CA, cornu ammonis; DG, dentate gyrus. P values represent mark-correlation (ae), mark-variogram (f,g) and E-mark (h) (two-sided, Benjamini–Hochberg adjusted).

Availabilityhttps://github.com/edsgard/trendsceek

Edsgärd D, Johnsson P, Sandberg R. (2018) Identification of spatial expression trends in single-cell gene expression data. Nat Methods [Epub ahead of print]. [abstract]

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