The technology disclosed relates to differential analysis of sets of time series pairs. In particular, it relates to building estimators of magnitude of difference between two time series. After the basic estimators are built, they are combined into ensemble estimators using linear or nonlinear prediction models to improve their accuracy. In one application, the ensemble is used for estimating the magnitudes of difference over sets of metric pairs observed from distributed applications and systems running over a computer network. The metric pairs are then ranked in decreasing order of magnitude of difference to guide an operator in prioritizing his root cause analysis of faults, thereby reducing the time-to-resolution of problems.