So, there is a manuscript called, "Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis."
Essentially, by exploiting huge amounts of data, the authors of that manuscript were able to leverage LD information to pinpoint the variants that actually produce the association of the MHC region in RA, rather than simply being passenger mutations.
The analyses took into account haplotype structure and several other layers of analysis, and ultimately pinpoint 3 variants (in HLA-A, -B, and -DRB1) all mapping to the peptide binding grooves of the respective molecules.
This purely in silico paper therefore represented a significant advance in biological understanding that wet lab techniques had not been successful in framing. Because the amino acids bear such resemblance, the manuscript has the effect of almost writing the next (very specific) hypothesis for the reader.
I was just curious as to any similar papers that you really enjoyed, and that sort of transcended experimental techniques to produce better understanding.
Anyone have examples? Have fun!