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In order to perform such an examination, a new dataset is constructed using previous results along with additional data retrieved from the Athens Stock Exchange website (http://www.ase.gr).gr

The hand curated dataset was constructed using two parallel approaches: The entire PDB was searched using Dockground server [23] in order to collect protein-protein complexes.

The ribosomal protein dataset was constructed using the composite database strategy, as described in [ 9].

The training dataset was constructed using 150 domain swapping and 150 non-domain swapping sequences.

Following Rot et al. [ 12], a LAGLIDADG dataset was constructed using BLASTP searches.

A second dataset was constructed using outbreak isolates genotyped by Aikimbayev et.al. [ 29].

The final analytic dataset was constructed using R software and statistical analysis was performed using SAS v9.3 and Joinpoint Regression Program [ 24].

An independent validation dataset was constructed using fresh frozen tumor tissue of 24 patients with an HNSCC originating from the oral cavity, the oropharynx, or the larynx.

We assembled two distinct datasets: our pathogenic dataset was constructed using heritable germ-line mutations from the Human Gene Mutation Database (Stenson et al., 2014) (release 2013.4, subsequently denoted HGMD) and our control dataset was constructed using SNVs from the 1000 Genomes Project (The 1000 Genomes Project Consortium, 2012).

One thousand bootstrap pseudo-datasets were constructed using the program seqboot, which was used as input into ProML that used a Hidden Markov Model method to infer evolutionary rates among residue positions [38] with the Jones, Talyor, and Thorton [39] probability matrix.

The randomized datasets were constructed using R version 3.1.1 [ 38].

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