We have already done some works in this relative field about gene network construction and analysis presented in our published papers [
15‐
19]. By integration of gene regulatory network infer (GRNInfer) and the database for annotation, visualization and integrated discovery (DAVID) we constructed significant molecule
TNFRSF11B development network and compared
TNFRSF11B up- and down-stream gene numbers of activation and inhibition between HIVE-control patients and HIVE (Table
1).
Table 1
Up- and down-stream gene numbers of activation and inhibition of each module with TNFRSF11B gene in TNFRSF11B development cluster between frontal cortex of HIVE-control patients and HIVE.
Apoptosis | 1 | 1 | | | 1 | 1 | | |
Signal Transduction | 2 | 1 | | | 4 | 4 | 4 | 5 |
Developmental Process | | | 2 | 0 | 0 | 6 | 4 | 4 |
In
TNFRSF11B developmental process of upstream network of frontal cortex of HIVE-control patients there was no result, whereas in that of HIVE, our integrative result reflected that
DGKG, PDCD4 activate
TNFRSF11B. In
TNFRSF11B developmental process of downstream network of HIVE-control patients, our integrative result illustrated that
TNFRSF11B inhibits
BST2, DGKG, GAS1, PDCD4, TGFBR3, VEZF1, whereas in that of HIVE,
TNFRSF11B activates
CFDP1, DGKG, GAS1, PAX6 and inhibits
BST2, PDCD4, TGFBR3, VEZF1 (Figure
1,
2; Table
2).
PAX6 is identified by molecular function of transcription factor, homeobox transcription factor, nucleic acid binding and DNA-binding protein, and it is involved in biological process of nucleoside, nucleotide and nucleic acid metabolism, mRNA transcription, mRNA transcription regulation, developmental processes, neurogenesis, segment specification and ectoderm development (DAVID database).
PAX6's relational study also can be presented in these papers [
20‐
25].
DGKG has been proved to be concerned with molecular function of kinase, and biological process of lipid, fatty acid and steroid metabolism, signal transduction, intracellular signaling cascade and lipid metabolism (DAVID).
DGKG's relational study also can be presented in these papers [
26‐
29].
GAS1's molecular function consists of mRNA processing factor, mRNA splicing factor, kinase modulator, dehydrogenase and kinase activator, and it is concerned with biological process of glycolysis, amino acid catabolism, pre-mRNA processing, mRNA splicing, cell proliferation and differentiation (DAVID database).
GAS1's relational study also can be presented in these papers [
30‐
33].
PDCD4 is relevant to molecular function of nucleic acid binding, translation factor, translation elongation factor and miscellaneous function, and biological process of protein metabolism and modification, protein biosynthesis, apoptosis, induction of apoptosis (DAVID).
PDCD4's relational study also can be presented in these papers [
34‐
39].
CFDP1 has been reported to have molecular function of mRNA splicing factor, select calcium binding proteins and KRAB box transcription factor, and to be concerned with biological process of mRNA transcription regulation and cell motility (DAVID database).
CFDP1's relational study also can be presented in these papers [
40‐
44]. We gained the positive result of
TNFRSF11B developmental process through the net numbers of activation minus inhibition compared with HIVE-control patients and predicted possibly the increase of
TNFRSF11B developmental process in HIVE.
Table 2
Activation and inhibition gene names of TNFRSF11B up- and down-stream development cluster in frontal cortex of HIVE-control patients and HIVE.
Developmental process | | |
DGKG, PDCD4
| |
Term
|
TNFRSF11B
downstream
|
|
con(act)
|
con(inh)
|
exp(act)
|
exp(inh)
|
Developmental process | |
BST2, DGKG, GAS1, PDCD4, TGFBR3, VEZF1
|
CFDP1, DGKG, GAS1, PAX6
|
BST2, PDCD4, TGFBR3, VEZF1
|
Importantly, we datamined that
TNFRSF11B development cluster of HIVE is involved in T-cell mediated immunity, cell projection organization and cell motion (only in HIVE terms) without apoptosis, plasma membrane and kinase activity (only in HIVE-control patients terms), the condition is vital to inflammation, brain morphology and cognition impairment of HIVE. Our result demonstrated that common terms in both HIVE-control patients and HIVE include developmental process, signal transduction, negative regulation of cell proliferation, RNA-binding, zinc-finger, cell development, positive regulation of biological process and cell differentiation, therefore we deduced the stronger
TNFRSF11B development network in HIVE consistent with our number computation. Some researchers indicated that tumor necrosis factor receptor studied to relate with inflammation, brain morphology and cognition [
45,
46]. Therefore, we predicted the stronger
TNFRSF11B development function in HIVE. It would be necessary of the stronger
TNFRSF11B development function to inflammation, brain morphology and cognition of HIVE.