Further advancement of RNA-Seq technology and its application call for the development of effective normalization methods for RNA-Seq data. Currently, different normalization methods are compared and validated by their correlations with a certain gold standard. Gene expression measurements generated by a different technology or platform such as Real-time reverse transcription polymerase chain reaction (qRT-PCR) or Microarray are usually used as the gold standard. Although the current approach is intuitive and easy to implement, it becomes statistically inadequate when the gold standard is also subject to measurement error (ME). Furthermore, the current approach is not informative, because the correlation of a normalization method with a certain gold standard does not provide much information about the exact quality of the normalized RNA-Seq measurements.