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20.07.2016

Masterarbeit/Bachelorarbeit

Am Institut für Funktionelle Genomik ist eine interdisziplin?re Masterarbeit/Bachelorarbeit für Biologen/Biochemiker/Chemiker oder Physiker im Bereich der NMR-basierten Metabolomik zu vergeben. Ziel der Arbeit ist die Unterscheidung verschiedener Nierenleiden anhand ihrer metabolischen Profile in Patienten mit chronischen Nierenerkrankungen (CKD). ... mehr


09.11.2015

Regression analysis based on metabolic data without prior normalization

Objective: Regression analyses based on biofluids such as plasma and urine usually require the prior application of appropriate normalization procedures to remove unwanted sample-to-sample variations. A newly “in house” developed algorithm shows promise to achieve these goals without prior normalization assuming that only linear shifts between data sets exists. In this exercise, the student is to systematically test this algorithm on various metabolic data sets and to compare it to existing methods. Test data sets were already acquired by means of NMR spectroscopy and hyphenated mass spectrometry. They were mostly obtained in context of various chronic and non-chronic kidney diseases. In case that tests proof to be successful wide spread application of the novel algorithm can be expected. During this exercise the student will gain knowledge in the statistical analysis of metabolic data and will also gain insight in the underlying biological background. ... mehr


09.11.2015

Extension of GSEA with the drug signature database DSigDB

Objective: In our inhouse R-package compdiagTools, we maintain an implementation of the Gene Set Enrichment Analysis (GSEA) by Subramaniam et al. containing the gene signature database MSigDB version 3.0 by Liberzon et al. This database contains gene sets related to Gene Ontology terms, KEGG pathways, genome positions, as well as signatures computed by cancer related microarray analysis. Our implementation of GSEA generates an HTML-page for each analysed gene set and an order of significant gene sets for a list of differential genes based on a microarray gene expression analysis. In this exercise, the student is to add additional gene sets related to drugs from DSigDB developed by Yoo et al. to our inhouse GSEA implementation. This implies the understanding of the corresponding R-package and the seamless integration of the DSigDB gene sets, including the adaptation of the corresponding user interface and its documentation. In addition to this programming task, gene sets from DSigDB are to be compared with the ones from MSigDB. Furthermore, differences in microarray analysis results on a microarray gene expression dataset are to be reported. ... mehr


09.11.2015

Prognostic impact of gene expression in lymphomas

Objective: The expression levels of genes can hold prognostic information on the clinical outcome (survival) of lymphoma patients. Today Diffuse Large B-Cell Lymphomas (DLBCL) are treated using the R-CHOP protocol, while some years ago the CHOP protocol was used. In this project we try to identify genes that indicate a good prognosis in R-CHOP treated patients and a poor prognosis in CHOP treated patients. This migh give additional insights into how the R-CHOP therapy works. Data: We use the data set of Lentz et al (2008). It consists of gene expression profiles and clinical data of both CHOP and R-CHOP treated patients. ... mehr


09.11.2015

Predicting proteomes from transcriptomes

Objective: In order to make a protein, a cell needs a mRNA. However, gene expression (mRNA quantities) and protein expression (protein quantities) correlate only weakly. Translation is regulated, and so is RNA processing as well as RNA and Protein degradation. All these processes affect mRNA and protein quantities and compromise the correlation between gene and protein expression. However, the regulating processes might leave their own traces in the expression of other genes. Here we aim at predicting the expression of proteins not only from the expression of the corresponding gene, but from the expression of all genes on a microarray.... mehr


09.11.2015

Predicting nanoString from Affymetrix data – non linear regression

Objective: Gene expression profiles from micro arrays can be used to diagnose tumors. However the experimental protocols are difficult and can only be carried out in large medical centers (like the DKFZ). nanoString is an alternative method to measure gene expression that is experimentally simpler and can be run in every small hospital. We want to move diagnostic signatures from the microarray platform to the nanoString platform. In a pilot study we have profiled 48 genes in 50 lymphomas using both technologies. The measurements for the same gene display a strong but non linear dependence. Here we want to use machine learning curve fitting procedures to predict potential nanoString data from microarray data. ... mehr


09.11.2015

Analyzing stromal lymphoma profiles

Objective: A lymphoma biopsy does not only consist of tumor cells. In addition there are typically cells from the tumor microenvironment (stroma). These include fibroblasts, epithelial cells from blood vessels and immune cells. If we extract RNA from the lymphoma tissue approximately 20%-30% of the total RNA is not from lymphoma cells. Some genes are only expressed in stromal cells, for them all RNA is stromal. Differences in the expression of these genes reflect the cellular composition of the lymphoma microenvironment. In this project we want to generate “pure” stromal profiles of lymphomas and analyze them.... mehr


09.11.2015

Predicting Interactions between microRNAs and mRNA

Objective: microRNAs (miRNAs) are short RNAs (~21-24 nt) which can bind to other mRNAs and regulate their abundances and thus affect various biological processes. Modern high-throughput technologies, allow to detect the paired expression of many RNAs and miRNAs. For paired expression profiles it was shown that by using a least angle regression approach the gene expression could be reconstructed from the miRNA expression and new interactions which can be associated with cancer [1] discovered. In this project, the approach described in [1] should be applied on newer and larger miRNA-mRNA datasets and the results compared to the previous outcomes.... mehr


09.11.2015

Use new sequencing technologies for faithful alignments and improved detection of differential expressed genes

Objective: Transcriptome data from a new sequencing platform, PacBio, are now available for the human cell lines MCF7, hESC H1 and GM12878. These data comprise full length transcript sequences of nearly all expressed transcripts in these cells. In current analysis workflows RNA-Seq data from Illumina is mapped to the genome and analysed with Tophat or Cufflinks which predict transcript isoforms from canonical splice sites, causing large numbers of false transcript isoforms. This happens especially with long genes containing many exons or genes containing intronic transposable elements. ... mehr


09.11.2015

Evaluation of genetic risk scores (GRS) of complex diseases and phenotypes in patients with age-related macular degeneration

Objective: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in individuals over 65 years of age. It is characterized by a progressive degeneration of the central retina conferred by genetic and environmental risk factors. The genetic risk of an individual to develop AMD has been quantified using a so called genetic risk score (GRS). Similar scores have been reported for other complex diseases, e.g. type II diabetes, cardiovascular disease or arteriosclerosis. In the proposed project, we want to investigate a potential overlap of the genetic risk (expressed as a genetic risk score) for AMD with the genetic risk of other complex diseases.... mehr


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