This is because the epigenetic signature in all fetal cells, including germ cells, is established during early development and the signature then interprets the information in the genetic code that is inherited from both parents by means that do not involve a change in DNA sequence [ 54].
As the maturity of spMNs grown in vitro compared to spMNs in vivo remains largely unaddressed, it is unclear to what extent this in vitro system captures critical aspects of spMN development and molecular signatures associated with ALS.
They attempt to detect malicious activity, but were designed when firewalls were at an earlier stage in their development and use techniques – signatures and noise – which generate resource-consuming false positives.
However, despite the resources allocated to their development and validation, prognostic signatures have proven to add limited information to prognostic models based on clinicopathological parameters and standardized assessment of ER, PR, HER2, and proliferation.
By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined.
Since no annotation for the 13th signature member was available at the time of the signature development, and to be consistent with the bootstrapping results, we replaced the 13th signature member by the 14th most frequently selected feature, TNFRSF10B, another p53 transcriptional target (Wu et al., 1997).
We start with a theoretical analysis that shows how the choice of four specific components of data analysis protocols for molecular signature development and their statistical testing affects the statistical power to detect predictive signal.
The Matlab code used for signature development and validation is provided in Supplementary Material.
Details on the development and validation of the signature and the corresponding prognostic score can be found in (Metzeler et al. 2008).
The development and use of such signatures might be of special interest when less well-characterised pathways are targeted, and knowledge about predictive markers is limited.
