rcorces
commented
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ArchR's
.addGeneScoreMatfunction incorrectly calculates what region flanking a gene to include in the gene score in the presence of fully overlapping genes.This issue affects about 16% of genes in the default ArchR Hg38 annotation. (I suspect this high count is due to the inclusion of many miRNA in the default annotation)
An example for debugging is the gene SYN2, which fully encloses the gene TIMP4 in ArchR's Hg38 gene annotation
To illustrate what happens, consider a pair of genes, one inside of the other:
ArchR will extend these gene regions as follows:
This is because
.addGeneScoreMatfinds neighboring genes by sorting based on start coordinate. So the outer gene sees the inner gene as its right-hand neighbor, and the inner gene sees the right-hand neigbor of the outer gene as its right-hand neighbor.What to do in the case of overlapping genes is a bit of a judgement call, but I'd propose extending as follows:
This could be easily implemented by removing fully enclosed genes prior to running the existing sort-based neighbor finding logic, and setting all fully enclosed genes to have the minimum flanking extension.