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We demonstrate a method of quantifying the penalty of in-band crosstalk that accounts for the varying spectral content. Experimentally evaluated penalties for widely varying crosstalk spectral content are shown to be readily predetermined based on the crosstalk spectral content and power within a single 112 Gb/s polarization-division multiplexing quadrature phase-shift keying (PDM-QPSK) link. Optical signal-to-noise ratio (OSNR) penalties predicted using a weighted crosstalk correlated with experimental results to within 1 dB for 8 spans AllWave [standard single-mode fiber (SSMF)] or TrueWave [nonzero dispersion fiber (NZDF)] links with different dispersion maps. Moreover, we identify a nonlinearity-enhanced crosstalk effect that is evident in the nonlinear transport regime and induce additional crosstalk-induced ONSR penalty.