# IFIH1 gene ontology analysis

The *Homo sapiens* interferon-induced helicase C domain-containing protein 1 (IFIH1) gene codes for the melanoma differentiation-associated protein 5 (MDA5). This plays an important role in the innate immunity being a pattern recognition receptor. MDA5 can recognize double-stranded (ds) RNA, a molecule that is not normally present in humans and other animals' cells. The ds-RNA is present in certain pathogens such as reovirus, rotavirus, birnavirus, etc. When the ds-RNA is detected, a signal mediated by the mitochondrial antiviral-signaling protein (MAVS) initiates the cytokines (interferons) clearing the virus by killing the infected host cells and participating in inflammation regulation.

By using gene ontology (GO) analysis a network model of the IFIH1 gene.

Figure 1. IFIH1 gene network created using Cytoscape Software with STRING layout. The yellow nodes and red edges represent a cluster of the first neighbor selected.

In order to visualize the GO of significantly over-represented categories within the selected gene, a GO enrichment analysis was created by using BiNGO tools (Figure 1 and Table 1).

Figure 2. Pathway of biological process related to the IFIH1 gene in the *Homo sapiens*. The yellow nodes shows the proteins that are over-represented (p>0.05) in biological proceses related with IFIH1 gene.

**Table 1. IFIH1 enriched GO terms**
| GO ID | description_MDA5 | pValue_MDA5 | adjustedPValue_MDA5 | N_MDA5 | nn_MDA5 | X_MDA5_ | xx_MDA5 | Degree |
|:-----:|:-------------------------------------------:|:-----------:|:-------------------:|:------:|:-------:|:-------:|:-------:|:------:|
| 51260 | protein homooligomerization | 1.56E-04 | 1.59E-02 | 14305 | 104 | 3 | 2 | 1 |
| 51259 | protein oligomerization | 5.22E-04 | 2.14E-02 | 14305 | 190 | 3 | 2 | 2 |
| 10815 | bradykinin catabolic process | 6.29E-04 | 2.14E-02 | 14305 | 3 | 3 | 1 | 1 |
| 50435 | beta-amyloid metabolic process | 1.05E-03 | 2.57E-02 | 14305 | 5 | 3 | 1 | 1 |
| 43171 | peptide catabolic process | 1.26E-03 | 2.57E-02 | 14305 | 6 | 3 | 1 | 3 |
| 42447 | hormone catabolic process | 1.89E-03 | 3.21E-02 | 14305 | 9 | 3 | 1 | 2 |
| 6461 | protein complex assembly | 3.67E-03 | 4.68E-02 | 14305 | 507 | 3 | 2 | 3 |
| 70271 | protein complex biogenesis | 3.67E-03 | 4.68E-02 | 14305 | 507 | 3 | 2 | 2 |
| 65003 | macromolecular complex assembly | 6.48E-03 | 6.01E-02 | 14305 | 676 | 3 | 2 | 3 |
| 43933 | macromolecular complex subunit organization | 7.42E-03 | 6.30E-02 | 14305 | 724 | 3 | 2 | 2 |
| 6518 | peptide metabolic process | 1.15E-02 | 6.39E-02 | 14305 | 55 | 3 | 1 | 2 |
| 22607 | cellular component assembly | 1.17E-02 | 6.39E-02 | 14305 | 913 | 3 | 2 | 3 |
| 44085 | cellular component biogenesis | 1.49E-02 | 7.25E-02 | 14305 | 1035 | 3 | 2 | 3 |
| 42445 | hormone metabolic process | 2.29E-02 | 1.02E-01 | 14305 | 110 | 3 | 1 | 3 |
| 10817 | regulation of hormone levels | 3.17E-02 | 1.35E-01 | 14305 | 153 | 3 | 1 | 2 |
| 9100 | glycoprotein metabolic process | 4.01E-02 | 1.55E-01 | 14305 | 194 | 3 | 1 | 2 |
| 16043 | cellular component organization | 8.48E-02 | 2.07E-01 | 14305 | 2563 | 3 | 2 | 3 |
| 44260 | cellular macromolecule metabolic process | 1.51E-01 | 2.53E-01 | 14305 | 3507 | 3 | 2 | 3 |
| 44248 | cellular catabolic process | 1.54E-01 | 2.53E-01 | 14305 | 776 | 3 | 1 | 3 |
| 43170 | macromolecule metabolic process | 1.92E-01 | 2.76E-01 | 14305 | 4016 | 3 | 2 | 2 |
| 9056 | catabolic process | 1.97E-01 | 2.78E-01 | 14305 | 1006 | 3 | 1 | 3 |
| 44237 | cellular metabolic process | 2.80E-01 | 3.76E-01 | 14305 | 4989 | 3 | 2 | 5 |
| 65008 | regulation of biological quality | 2.90E-01 | 3.79E-01 | 14305 | 1542 | 3 | 1 | 2 |
| 8152 | metabolic process | 3.76E-01 | 4.51E-01 | 14305 | 5958 | 3 | 2 | 5 |
| 65007 | biological regulation | 4.78E-01 | 5.30E-01 | 14305 | 6943 | 3 | 2 | 2 |
| 9987 | cellular process | 7.25E-01 | 7.32E-01 | 14305 | 9369 | 3 | 2 | 2 |
| 8150 | biological_process | 1 | 1 | 14305 | 14305 | 3 | 3 | 5 |

By using the enrichment network analysis I learned that MDA5, the protein encoded by IFIH1, plays a role in the different interconnected biological processes. In the center of the network is the biological process node that generates sub nodes. There are eight processes that are over-represented (yellow nodes in figure 2) and they are listed in table 1 based on their hierarchy. Interestingly, all of these processes are not directly interconected with each other. There are four connected over-represented nodes: protein homooligomerization; protein oligomerization; protein complex assemby and protein complex biogenesis, that are part of cellular component biogenesis and macromolecular complex assembly. There are two connected over-represented nodes: peptide and bradykinin catabolic processes that belong to a cellular metabolic process which generates a cellular macromolecule metabolic process that gives origin to another over-represented node: the beta-amyloid metabolic process. Finally the hormone catabolic process is part of a metabolic process that is related with hormone regulation. In conclusion, the MDA5 protein encoded by IFIH1 gene plays diverse roles in biological processes not only limited to the immune system.

### References
Maere S, Heymans K, Kuiper M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in biological networks. Bioinformatics 21, 3448-3449
The UniProt Consortium (2019). UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 47: D506-515
Doncheva NT, Morris JH, Gorodkin J, Jensen LJ. (2019) Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data. J Proteome Res. 18(2):623-632