The Yule-Nielsen modified spectral Neugebauer model enhanced for accounting for ink spreading in the different ink superposition conditions (EYNSN) requires measuring the reflectances of halftone calibration patches in order to compute the ink spreading curves mapping nominal ink surface coverages to effective ink surface coverages. Spectral measurements of dozens of halftone patch reflectance spectra for each considered halftoning method, screen shape or screen frequency variant is cumbersome and time consuming. As an alternative, we compute automatically the reflectance of the calibration patches necessary to establish the ink spreading curves by making use of the two-by-two dot centering model (abbreviated “2-by-2”). The two-by-two dot centering model requires its own set of calibration patches, among which a very small subset is necessary for predicting the reflectance of the EYNSN calibration patches. For a given combination of printer, paper and inks, using only 68 two-by-two calibration patches for the three CMY inks, respectively 118 two- by-two calibration patches for the four CMYK inks, we are able to predict the reflection spectra of most classical halftone screens and at many different frequencies. We compare the results of predictions where the EYNSN model calibration patches are measured or are predicted with the two-by-two dot centering model. For 125 (CMY) and 625 (CMYK) uniformly distributed patches printed with an ink-jet printer at three different screen frequencies (75lpi, 100lpi and 125lpi), the mean reflectance prediction accuracy is similar, i.e. the decrease in accuracy due to the two-by-two prediction of EYNSN calibration patch reflectance is less than ΔE94=0.4.