One of the major limitations of a gene expression analysis study is the lack of empirical evidence for functionality of any of the identified candidate genes that may cause an aberrant phenotype or enhance a trait of interest.
Although evidence of functionality of specific lncRNAs continues to accumulate, conflicting, confusing, and overlapping terminology has fostered ambiguity and lack of clarity in the field in general.
SNP selection was balanced between literature-based evidence of functionality and apparent signatures of selection.
We thus already restricted the presented pathway analyses to variants with strong evidence of functionality.
Whilst strongly suggestive, does filtering for variants with strong evidence of functionality alter these conclusions?
Direct evidence of functionality has also been reported for some pseudogenes.
Evidence of functionality requires assays of T cell proliferation or cytokine production for the given HLA-peptide complex.
Studies that also included experiments providing evidence of functionality for associated variant(s) were scored as adequate.
However, whenever possible functionality should be supported with a Ka/Ks significantly <1 or Ka/Ks significantly >1 for the particular orphans to provide additional evidence of functionality.
Rather, we looked for consistency of association across the different studies that reported results for a particular SNP, as well as evidence of functionality.
As a result, many cis-element sequence data in these databases include superficial core motifs for which no evidence of functionality has been obtained.
