The expected fraction of hotspot (or non-hotspot) mutations in the functional region type (p2) is the fraction of the genome that constitutes the functional region. The observed fraction of hotspot (or non-hotspot) mutations in the functional region is calculated by adding all mutations in the functional region type and dividing by the total number of mutations genome-wide (p1). The log odds ratio of the enrichment of hotspot (or non-hotspot) mutations in a functional region type is given by,\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm{LOD} = {\mathrm{ln}}(\frac{{p_1/(1 - p_1)}}{{p_2/(1 - p_2)}})$$\end{document}LOD=ln(p1∕(1-p1)p2∕(1-p2))The standard error of the LOD is calculated as,\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm{SE}}_{\mathrm{LOD}} = \sqrt {\frac{{{{\mathrm{SE}}_{p1}}^2}}{{{p_1}^2 - \left( {1 - p_1} \right)^2}} + \frac{{{{\mathrm{SE}}_{p2}}^2}}{{{p_2}^2 - \left( {1 - p_2} \right)^2}}}$$\end{document}SELOD=SEp12p12-1-p12+SEp22p22-1-p22The statistical significance of the enrichment was evaluated by the Z-test.