Gauge fixing for sequence-function relationships.

Computational biology relies heavily on mathematical models that predict biological activities from DNA, RNA, or protein sequences. Interpreting the parameters of these models, however, remains difficult. Here we address a core challenge for model interpretation-the presence of 'gauge freedoms', i.e., ways of changing model parameters without affecting model predictions. The results unify commonly used methods for eliminating gauge freedoms and show how these methods can be used to simplify complex models in localized regions of sequence space. This work thus overcomes a major obstacle in the interpretation of quantitative sequence-function relationships.