Optimization-based predictive models in medicine and biology

Summary We present novel optimization-based classification models that are general purpose and suitable for developing predictive rules for large heterogeneous biological and medical data sets. Our predictive model simultaneously incorporates (1) the ability to classify any number of distinct groups; (2) the ability to incorporate heterogeneous types of attributes as input; (3) a high-dimensional data transformation that eliminates noise and errors in biological data; (4) the ability to incorporate constraints to limit the rate of misclassification, and a reserved-judgment region that provides a safeguard against over-training (which tends to lead to high misclassification rates from the resulting predictive rule); and (5) successive multi-stage classification capability to handle data points placed in the reserved judgment region. Application of the predictive model to a broad class of biological and medical problems is described. Applications include: the differential diagnosis of the type of erythemato-squamous diseases; genomic analysis and prediction of aberrant CpG island meythlation in human cancer; discriminant analysis of motility and morphology data in human lung carcinoma; prediction of ultrasonic cell disruption for drug delivery; identification of tumor shape and volume in treatment of sarcoma; multistage discriminant analysis of biomarkers for prediction of early atherosclerosis; fingerprinting of native and angiogenic microvascular networks for early diagnosis of diabetes, aging, macular degeneracy and tumor metastasis, and prediction of protein localization sites. In all these applications, the predictive model yields correct classification rates ranging from 80% to 100%. This provides motivation for pursuing its use as a medical diagnostic, monitoring and decision-making tool.