Return to search

Detection of KRAS Synthetic Lethal Partners through Integration of Existing RNAi Screens

KRAS is a gene that plays a very important role in the initiation and development of several types of cancer. In particular, 90% of human pancreatic cancers are due to KRAS mutations. KRAS is difficult to target directly and a promising therapeutic path is its indirect inactivation by targeting one of its Synthetic Lethal Partners (SLPs).

A gene G is a Synthetic Lethal Partner of KRAS if the simultaneous perturbation of KRAS and G leads to cell death. In the past, efforts to identify KRAS SLPs with high-throughput RNAi screens have been performed. These studies have reported only few top-ranked SLPs. To our knowledge, these screens have never been considered in combination for further examination.

This thesis employs integrative analysis of the published screens, utilizing additional, independent data aiming at the detection of more robust therapeutic targets.

To this aim, RankSLP, a novel statistical analysis approach was implemented, which for the first time
i) consistently integrates existing KRAS-specific RNAi screens,
ii) consistently integrates and normalizes the results of various ranking methods,
iii) evaluates its findings with the use of external data and iv) explores the effects of random data inclusion.

This analysis was able to predict novel SLPs of KRAS and confirm some of the existing ones.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:14-qucosa-158069
Date18 December 2014
CreatorsChristodoulou, Eleni
ContributorsTechnische Universität Dresden, Fakultät Informatik, Prof. Dr. Michael Schroeder, Prof. Dr. Andreas Beyer, Prof. Dr. Annalisa Marsico
PublisherSaechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typedoc-type:doctoralThesis
Formatapplication/pdf

Page generated in 0.002 seconds