1. A method of assigning the risk of progression of Barrett's esophagus to a subject, comprising: a) obtaining an upper gastrointestinal sample from the subject, wherein the upper gastrointestinal sample comprises one or more of the following tissues: surface epithelium, glandular epithelium, lamina propria, and stroma; b) labeling a plurality of biomarkers using fluorescent probes, stains, or antibodies in the upper gastrointestinal sample from the subject, wherein the plurality of biomarkers are selected from the group consisting of p53, HIF-1alpha, beta-catenin, COX-2, and any combination thereof; c) detecting the labeled biomarkers and nuclei with an optical scanner; d) generating digital image data from the detected labeled biomarkers and nuclei; e) storing the generated digital image data in a computer-readable storage medium; f) analyzing the digital image data with a computer processor implementing computer-executable program code to produce pixel-based segmentation and object-based classification of subcellular compartments and tissues; g) quantifying one or more descriptive features of each biomarker and nuclei, wherein the descriptive features are selected from the group consisting of mean intensity in a cell-based object including cell, cytoplasm, plasma membrane, and nucleus; and ratio of intensity between cell-based objects including cell, cytoplasm, plasma membrane, and nucleus; h) converting the analyzed and quantified digital image data to generate a score using a predictive statistical model developed in a set that comprises disease cases and unaffected controls, wherein the score is computed by linear combination of descriptive features weighted by coefficients obtained via linear regression model, and the score is correlated to a risk of progression to high grade dysplasia or esophageal adenocarcinoma; and i) using the score to identify which subjects to treat; wherein the subject with a high risk score is treated using a clinical treatment selected from the group consisting of endoscopic surveillance, endoscopic mucosal resection, radiofrequency ablation, and any combination thereof; and wherein the subject with a low risk score is not treated and avoids unnecessary invasive procedures and continues endoscopic surveillance at reduced frequency or discontinues endoscopic surveillance.