Analyzing stromal lymphoma profiles

Status: selected

Praktikum (Bachelor/Master)

Field: Genomics, Data Analysis

Advisors: Spang, Kohler

Courses Required: Practical Bioinformatics I

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.

Data: We have more than 900 expression profiles of lymphoma tissues and 20-30 profiles of pure tumor cell lines.

First Steps:

• Get familiar with the lymphoma data sets including the phenotype data tables and the cell line data sets
• Detect genes that are highly expressed in lymphoma tissue but not in pure lymphoma cell lines.
• Using only this restricted stromal gene expression data set, reanalyze the lymphoma data set.
• Download cell line data of pure stromal cell types and try to identify the cell of oorigin of  the stromal genes

 Questions:   Which genes are expressed only in the stroma? From which stromal cells can they come? Can lymphoma subtypes (mBL, GCB, ABC, FL, etc.) be distinguished based on stromal gene expression? Does clustering the cases using only stromal gene expression reveal new lymphoma subtypes? Are their clinical differences between these subtypes?

Start reading:

Hummel et al. NEJM 2005

Lenz et al. NEJM 2008