The present invention provides methods of detection, including early detection, for cancer or other diseases and normal physiologic processes mediated by global epigenetic changes, by using one or more of the following biomarkers: a global DNA methylation index, a global histone H4 acetylation index, and a global histone H4 trimethylation index. These methods are useful for, among other things, assessing the effectiveness of treatment, monitoring relapse, and clinical staging of cancer and other chronic as well as acute diseases. These methods are also useful for among other things monitoring the effectiveness of strategies and therapies used to modify lifestyle and contextual effects to prevent disease, foster wellness and enable health promotion.