Team:Linkoping/Implementation



Implementation

We as a team hope that ClusteRsy will be used by clinicians and future iGEM teams. The user-friendliness of our software will entice new users to begin with transcriptomic analysis and that the knowledge needed to start the analysis has substantially been lowered. As with any analysis software, knowledge of the input and what to expect of the output is needed. With the ClusteRsy software and the designed workflow with the following youtube tutorial, we wish to open up the wonders of transcriptomic analysis. Below we have listed a few areas where we believe our project will have an impact.

”Alttext”
Figure 1. Overview of ClusteRsy workflow leading to further applications.


Biomarker discovery

The result of ClusteRsy is a network of differentially expressed genes and pivotal information of each gene which is a key aspect when discovering a potential biomarker. With a network, the user can see interacting factors of each gene and get a broader understanding of all interactions. ClusteRsy enables the user to download the output as a Cytoscape object making it easy for the user to visually analyze the output of ClusteRsy.



Transcriptomic analysis of designed bacterial cultures

ClusteRsy is not specific to any organism and we aim to add PPI networks of bacterial, yeast, and mammalian expression systems for future iGEM teams to analyze the transcriptomics of designed systems. This to further enable iGEM teams to understand and to optimize their expression systems.



Visualizing disease patterns

The two beta-testings and meetings with clinicians such as Maria Jenmalm, Sofia Nyström, and Jan Ernerudh have given important critique and insight into the understanding of disease patterns. With the received critique in mind, we have created and updated ClusteRsy to be as functional as possible and streamlined the workflow to be intuitive and informative. With advanced algorithms for transcriptomics analysis of ClusteRsy and the integration of Cytoscape to easily visualize the results, we hope that it will further help to understand diseases.



Screening infants for RSV risk factors

In the results of the modeling we have found a correlation between asthma and the Respiratory syncytial virus (RSV) and the genes involved. The correlation is known since before, but the genetics and specific molecular interactions are still unknown [1]. It has been shown that the leading cause of asthma is if the patient has been sick from the RSV virus when being an infant.

The results from the modeling were shown to Maria Jenmalm, a professor in Experimental Allergology and she thought the results were very interesting. With the now known genetics, it would have clinical significance to screen infants to see if they are in the risk group being prone to develop serious complications from the RSV virus, one of them being asthma.

Born infants inherit lgG antibodies from the mother, but due to the short half-life of lgG antibodies, infants lack immunity after three months leaving them vulnerable to infections. This in combination with a genetic set-up susceptible to severe RSV bronchiolitis makes it even more important to screen infants.

Since there is no vaccine towards RSV the medication palivizumab has been proven to prevent RSV infection [2]. Infants in the risk group can be given a monthly shot of palivizumab during peak RSV season to protect these infants from getting sick and developing serious complications.

References

[1]. Thomsen SF, van der Sluis S, Stensballe LG, Posthuma D, Skytthe A, Kyvik KO, Duffy DL, Backer V, Bisgaard H. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study. Am J Respir Crit Care Med. 2009 Jun 15;179(12):1091-7. doi: 10.1164/rccm.200809-1471OC. Epub 2009 Mar 12. PMID: 19286626.

[2]. Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, Quero J. Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J. 2003;22(9):823-7. doi: 10.1097/01.inf.0000086403.50417.7c. PMID: 14506376.