Proposed HCC epigenetic drugs are represented by inhibitors of DNMTs [ 95– 97] and histone deacetylases [ 98, 99] that, by interfering with epigenetic regulators activities, simultaneously affect multiple target genes.
In the linear model (1) e represents a vector of gene expression measurements across m conditions, S is a m × k matrix of the k regulators' activities and c is a sparse vector that represents the interaction between the gene and regulators.
We determined that the eigenvector-derived profiles of regulators' activity fully recapitulate NCA profiles.
Furthermore, the direct measurement of the regulators' activity is a challenging and expensive, if not an impossible, task.
However, Sall2-regulated genes in the categories of catalytic and enzyme regulator activities are exceptionally unbalanced, with 1.6-fold more of the upregulated genes than the downregulated genes.
The molecular function category was dominated by binding, catalytic, transporter, transcriptional regulator and enzyme regulator activities.
The most frequently reported events using the terminology of the Medical Dictionary for Regulator Activities (MedDRA) were headache, diarrhoea, nausea, abdominal pain, and influenza.
In fact, the current model is an open loop system, such that the regulation of regulator activity is itself viewed as exogenous to the system.
The GO terms related to regulation: biological regulation (4%), enzyme regulator activity (4%), and transcription regulator activity (4%) as well as proliferation: cell proliferation (4%), demonstrated the lowest percentage values.
Using a modified method from Freilich et al. [ 4], we grouped genes into four main categories according to their GO annotation: enzymatic activity, transporter, regulation (including transcription regulator activity, translation regulator activity, and enzyme regulator activity), and signal transduction.
In the absence of any scaffold protein, no activated response regulator activity is observed (Supplementary Figure S2, Supporting Information).
