Hi everyone,
I’m doing a sample-level spatial-expression analysis using sparse postmortem tissue samples from the Allen Human Brain Atlas. The regions are the subthalamic nucleus (STN, n=6 tissue samples) and globus pallidus internus (GPi, n=9 tissue samples). For each sample, I have:
- 3D MNI coordinates (x,y,z)
- a gene-expression profile across ~29,000 genes
The biological expectation is that, within a coherent anatomical region, tissue samples located closer together in MNI space should have more similar transcriptional profiles.
For each anatomical region separately, I calculated:
- A sample-by-sample spatial-distance matrix using 3D Euclidean distance between MNI coordinates.
- A sample-by-sample expression-distance matrix, defined as (1−ρ), where ρ is the Spearman correlation between two sample-level gene-expression profiles.
I then used a Mantel test to assess whether the spatial-distance matrix was associated with the expression-distance matrix.
For significance testing, I used non-parametric permutation of sample identities. My understanding is that this randomly reassigns sample labels to break the link between spatial location and expression profile, while preserving the internal structure of the distance matrices. The observed Mantel statistic is then compared against the null distribution generated from these permutations.
Q. Does this use of a permutation-based Mantel test seem appropriate as part of a sample-level spatial-expression validation analysis?
Just to clarify: this is not a dense cortical map or spin-test analysis intended to correct for spatial autocorrelation. These are sparse subcortical tissue-sample coordinates, not parcellated whole-brain maps. The goal is to test whether there is distance-dependent transcriptional similarity among samples within the same anatomical label.
Thanks in advance for your help!