A sound epistemological foundation for biological inquiry comes, in part, from application of valid statistical procedures. This tenet is widely appreciated by scientists studying the new realm of high-dimensional biology, or 'omic' research, which involves multiplicity at unprecedented scales. Many papers aimed at the high-dimensional biology community describe the development or application of statistical techniques. The validity of many of these is questionable, and a shared understanding about the epistemological foundations of the statistical methods themselves seems to be lacking. Here we offer a framework in which the epistemological foundation of proposed statistical methods can be evaluated.