Prioritization of pharmacological compounds for tumor immunogenic profile manipulation using next-generation sequencing data

Κατωπόδη, Ξανθή-Λήδα; Katopodi, Xanthi-Lida

dc.contributor.author	Κατωπόδη, Ξανθή-Λήδα	el
dc.contributor.author	Katopodi, Xanthi-Lida	en
dc.date.accessioned	2020-12-15T10:31:03Z
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/52532
dc.identifier.uri	http://dx.doi.org/10.26240/heal.ntua.20230
dc.rights	Default License
dc.subject	Cancer	en
dc.subject	Next-Generation sequencing data	en
dc.subject	Immunotherapy	en
dc.subject	Immunoinformatics	en
dc.subject	Pharmacological compounds	en
dc.subject	Καρκίνος	el
dc.subject	Ανοσοθεραπεία	el
dc.subject	Βιοπληροφορική ανοσοποιητικού συστήματος	el
dc.subject	Δεδομένα αλληλούχισης επόμενης γενεάς	el
dc.subject	Φαρμακολογικές ουσίες	el
dc.title	Prioritization of pharmacological compounds for tumor immunogenic profile manipulation using next-generation sequencing data	en
heal.type	bachelorThesis
heal.classification	Bioinformatics	en
heal.dateAvailable	2021-12-14T22:00:00Z
heal.language	en
heal.access	embargo
heal.recordProvider	ntua	el
heal.publicationDate	2020-10-09
heal.abstract	Cancer is the second leading cause of death worldwide and one of the most well- researched medical topics. Nevertheless, the lack of effective treatment for the majority of tumor types is evident, while existing therapeutic approaches are unable to guarantee desired results. In the frame of this diploma thesis, a novel holistic approach is adopted for the discovery of drugs, compounds, and gene targets that can alter the immunogenic profile of tumors and expand the arsenal of immunotherapeutics. The approach described in this study comes as a means to eradicate the current limitations of existing immunotherapies and improve their efficiency. In general, immunotherapy leverages components of the immune system in order to boost its ability to detect and destroy malignant cells. Unfortunately, only a small fraction of patients respond to immunotherapy, with the primary reason being the ability of tumor cells to bypass the immune system’s control. Thus, it is essential for the improvement of existing immunotherapies that the tumor emanates its malignant nature in order for the immune system to detect and combat cancer cells. The proposed method is based on the existence of Tumor Specific Antigens (TSAs) that can elicit an immune response. The hypothesis made is that personalized gene targeting and drug administration are able to manipulate the antigenic profile of tumor cells as they will allow for the controlled generation of strongly immunogenic TSAs; such TSAs will act as targets for the immune system. Following this approach, tumors that were able to escape the control of the immune system can now be sensitized to immunotherapy. For this purpose, a plethora of publicly available Next Generation Sequencing (NGS) studies were analyzed to reveal tumor-specific antigens whose production was induced following drug administration or gene targeting. An annotation-free and hypothesis-free approach to capture the expression and translation spaces was incorporated, allowing for unbiased characterization of the putative antigen spaces. After comparison of the two spaces to sets of data derived from healthy samples, results revealed significant cancer- specific effects on the transcriptome and translatome. Furthermore, the effect of treatment on the expression space was also evident on all three case studies included in the study, both in the number of treatment-specific transcripts and in the expression change between treatment and control. Last but not least, the implementation of a database structure was initiated which will enable efficient storing of analyzed results and cross-study comparisons.	en
heal.advisorName	Μπουντουβής, Ανδρέας	el
heal.committeeMemberName	Μπουντουβής, Ανδρέας	el
heal.committeeMemberName	Vlachos, Ioannis S.	en
heal.committeeMemberName	Ζουμπουλάκης, Λουκάς	el
heal.academicPublisher	Εθνικό Μετσόβιο Πολυτεχνείο. Σχολή Χημικών Μηχανικών	el
heal.academicPublisherID	ntua
heal.numberOfPages	66 σ.	el
heal.fullTextAvailability	false
heal.fullTextAvailability	false