Sunday, December 7, 2014

Ingenuity Pathways

Ingenuity Pathways

IPA ingenuity is a program that helps to unlock the relationships between genes and relevant pathways. Utilizing IPA pathways, I was able to locate my gene, FBN1. Upon the initial search, there does not appear to be any drugs that are associated with the product of FBN1 (as depicted below).

IPA Pathway: FBN 1. Absence of drug interactions. 

When I grew a pathway using my gene and constraining the relationships to direct relationships using all molecules, human species data, and removal of chemical and biological drugs, the following image was obtained with identification of 3 molecules and 3 relationship. The 3 molecules are TP63, MMP25, VCAN.

FBN1 pathway with listed constraints : 3 pathways identified


Since only 3 relationships were observed, I did not need to apply the trim instructions. The following is the screen shot of the pathway after applying “autolayout”.  

Autolayout of selected FBN1 pathways


There are 3 different types of relationship types for the 3 molecules identified. For example, TP63 has an "expression" relationship, MMP25 has a "molecular cleavage" relationship, and VCAN has a protein - protein interaction.  Binding of human FBN1 protein and a protein fragment containing a C-type lectin domain from human VERSICAN (VCAN) protein occurs in a system of purified components from A204 cells. Therefore, there is one protein-protein interaction and no activation or inhibition relationships. 


Protein-protein interaction between VCAN and FBN1


Molecular cleavage relationship of MMP25 to  FBN1

Expression relationship of TP63 to FBN1



Using the "Toggle SubcellularLayout" it is evident that the FBN1 gene is located in the extracellular space along with VCAN. MMP25 is located in the plasma membrane. TP63 increases the expression of human FBN1 mRNA and is appropriately located in the nucleus of cells.



Subcellular layout of FBN1 and related pathways



Overlay Canonical Pathway

Using the canonical pathway function, there was no single pathway that included FBN1 (as seen below). So I chose to proceed with assessing TP63  for the p53 signaling pathway.
Canonical pathways
The p53 signaling pathway is depicted below with a close up of where TP63 is in relation to the pathway. According to the pathway report, the p53 (TP53)  tumor suppressor protein is a key transcriptional regulator that responds to a variety of cellular stresses such as DNA damage, UV irradiation, and hypoxia. the p53 gene regulates key cellular processes such as DNA repair, cell-cycle progression, angiogenesis, and apoptosis. Loss of p53 is thought to be a contributing factor to cancer. 

p53 signaling pathway

Location of p63 in the p53 signaling pathway