MSc Thesis – Analysis of protein-DNA interactions from ChIP-seq data

Remark

This thesis will be a joint project of the Algorithmische Bioinformatik group at FU-Berlin and the Cardiovascular Genetics group (http://www.molgen.mpg.de/~heart/index.htm) at the Experimental and Clinical Research Center (ECRC). The focus of this thesis is on the application of existing software and data analysis.

Topic

Chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) has become the method of choice to investigate genome-wide in vivo binding pattern of transcription factors (TFs) and chromatin histone marks. In the group of Prof. Dr. Silke R. Sperling, ChIP-seq data were generated from different TFs and chromatin remodeling factors (Hey1, Gata4, Dpf3, MyoD, Brg1, Baf60c) as well as histone modifications (H3ac, H3K4me1/2/3, H3K36me3, H4K16ac) in HL1 cells (mouse cardiomyocytes) and C2C12 cells (skeletal muscle cells). Aim of this master thesis is the ChIP-seq data analysis which is divided into (I) quality control of next- generation sequencing data, (II) mapping of the obtained sequenced reads to the reference genome, (III) normalization of read counts to account for experimental differences between different sequencing runs, (IV) calling of enriched sites (peaks) and (V) the discovery of sequence binding motifs.

Timeline

There will be regular meetings to discuss progress and problems.

References

[1] The Cardiac Transcription Network Modulated by Gata4, Mef2a, Nkx2.5, Srf, Histone Modifications, and MicroRNAs. Schlesinger J, Schueler M, Grunert M, Fischer JJ, Zhang Q, Krueger T, Lange M, Tönjes M, Dunkel I, and Sperling SR. PLoS Genet 7(2): e1001313.

[2] Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. Lange M, Kaynak B, Forster UB, Toenjes M, Fischer JJ, Grimm C, Schlesinger J, Just S, Dunkel I, Krueger T, Mebus S, Lehrach H, Lurz R, Gobom J, Rottbauer W, Abdelilah-Seyfried S, and Sperling RS. Genes & Development 22(17):2370-84 2008.

[3] Identifying ChIP-seq enrichment using MACS. Feng J, Liu T, Qin B, Zhang Y, Liu XS. Nat Protoc. 2012 Aug 30;7(9):1728-40.

[4] Model-based analysis of ChIP-Seq (MACS). Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, Liu XS. Genome Biol. 2008;9(9):R137.

[5] http://www.bioinformatics.babraham.ac.uk/projects/fastqc/

[6] http://www.oxfordjournals.org/our_journals/bioinformatics/nextgenerationsequencing.html