Breast cancer with bone metastasis

[ddolbae01]

I've already told my curiosity to Professor Yoo and Efrain.


I was curious about the order scores of parameters that have same position of target node with different parents orders or child orders.

I selected the 6 nodes with same trail in the Banjo graph (60 nodes).

The nodes are linked with edge as follow.


predecessor node (ARHGEF1; 0) - predecessor node (HOXA10; 1) - parent node (FRAT2; 2) - Target node (Group; 3) - child node (RPS6KB2; 4) - descendant node (FH; 5)


After running the Efrain order code,

the score of order as 0 1 2 3 4 5 , 5 number of parent was -305.725

the score of order as 1 0 2 3 4 5 was -305.725

the score of order as 2 1 0 3 4 5 was -305.725

the score of order as 5 4 3 2 1 0 was -256.336

the score of order as 4 5 3 2 1 0 was -256.336


upper three orders have same score....
I hope my curiosity help Efrain works.

[ddolbae01]

I tried to integrate the biological information into 1st degree Markov Blanket in this week.
Then, I found the nodes in the 1st degree MB had several biological relationships.
I attached the word file with figures and short comments about the study results.

The nodes in the structure are as follows (Fig 1.).
Three parents nodes are FRAT2, MAP2K2, and MEIS1.
Target node is Group (the presence of bone metastasis of breast cancer).
Five child nodes area TGFB3, LDHA, RPS6KB2, GNAS, and RPS6.
Six co-parent nodes are DVL1, HRAS, RASSF1, RCYT1A, HIST1H3G, SCO2, and ECT2.

I converted the 1st degree MB of Banjo structure into cytoscape graph (Figure 2).
Cytoscape can show us the genes and related pathways.
Among 16 genes in 1st MB, 12 genes had pathways registered in KEGG.

General Findings
1. FRAT2, MAP2K2, RPS6KB2, HRAS, DVL1 are Breast cancer related genes.

2. MAP2K2, RPS6KB2, RPS6, DVL1, HRAS are mTOR related genes (Figure 3).
* mTOR pathway has the strong relationship with cancer, cancer progression and poor prognosis.
* PI3K/Akt/mTOR and Ras/MEK/ERK pathways play a central role in many human cancers.

3. MEIS1,parent node gene, is oncogene related with breast cancer
FRAT2, parent node gene, is related with tumor progression.

4. LDHA, child node gene is related with the activation of metabolism of cancer cells.
TGFB3, child node gene is related with tumor progression and metastasis.
The mutation of GNAS, child node gene is related with cancer.

5. Co-parents node genes
The mutation of HRAS is related with cancer
DVL1 is related with cancer development
RASSF1 is tumor suppressor gene
SCO2 is counter gene of p53 tumor suppressor gene.
HIST1H3G is epigenetic factor related with cancer (may be related EMT)
ECT2 is related with malignant transformation of tumor
PCYT1A is related with good prognosis.

In summary, the genes in 1st MB can be classified several groups as follows
1. PI3K/Akt/mTOR and Ras/MEK/ERK pathway
2. Activation of metabolism of cancer cells
3. Gene mutation or oncogen
4. epigenetic factor as EMT (epithelial to mesenchymal transition)

Now, I am going to make GeNIe graph using the nodes in 1st degree MB. and try to find a probabilistic graphical model.
I expect the probabilistic model may predict the occurrence of bone metastasis of breast cancer well.

[ddolbae01]

I performed the order analysis using the recent Efrain's order code.
The program ran 6 times for analysing three sets as no prior set (6hrs vs 24 hrs analysing time), a prior set (3hrs vs 24hrs) and other prior set (3hrs vs 24hrs).

Among 6 sets analyses, the no prior with 24 hrs analysing time had the result with best score (-730.3982).
I attached the result.

[ddolbae01]

The study result for osteolytic metastatic bone has been accepted to journal of bone metabolism (https://www.e-jbm.org/)
The title is Causal inference network of genes related with bone metastasis of breast cancer and osteoblasts using causal Bayesian networks
I deeply thanks to Professor Yoo, Professor Roy and Efrain.

I attached the final manuscript.