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Table 3 Experimental data platforms to estimate cell sizes and calculate cell size scaling factors to adjust for systematic differences in size and transcriptomic activity between cell types. The table contains the type of experimental data (column 1), the metric used for cell size (column 2), a set of standards (gold, silver, and bronze) introduced by Dietrich et al. [20] (column 3), the format for how the data are captured (column 4), example data analysis challenges when using these data (column 5), and if the experimental data are orthogonal to using sc/snRNA-seq (column 6)

From: Challenges and opportunities to computationally deconvolve heterogeneous tissue with varying cell sizes using single-cell RNA-sequencing datasets

Experimental data

Cell size metric

Standard [74]

Data format

Data analysis challenges

Orthogonal to sc/snRNA-seq

FISH [4, 78,79,80]

Label intensity

Gold

Image

Label performance; cell segmentation; image artifact removal [22, 28, 35, 40, 74]

Yes

IHQ/IHC [36]

Label intensity

Gold

Yes

Labeled expression marker [79, 80]

Expression/label intensity

Silver

Yes

sc/snRNA-seq

mRNA spike-in expression

Silver

Gene expression counts

Embedding alignment, batch effects, dissociation biases, platform biases [26, 48, 81]

Yes

sc/snRNA-seq

Housekeeping gene expression

Silver

No

sc/snRNA-seq

Library size [36, 78, 82]

Bronze

No

sc/snRNA-seq

Expressed genes [36, 78, 82]

Bronze

No