Multi-Split-Mapping of NGS reads for variant detection

Student
Sabrina Krakau

Academic Advisor
Prof. Dr. Knut Reinert, Anne-Katrin Emde

Expose

The goal of this thesis is to design, implement and test a “bisulphite mapping ” method that

1. maps bisulphite treated reads to a reference genome
2. determines the boundaries of the unmethylated/methylated regions
3. compares speed and sensitivity using simulated and real data (from the honey bee)

The thesis should also result in a comprehensive analysis pipeline which conducts read mapping for the easy cases (completely methylated resp. completely unmethylated) and then develops a method for reads that are partially methylated.

The main steps of the algorithm could be:

1. generate local matches on the methylated and unmethylated genome for all reads
   • using STELLAR
   • optional: using external matches (code should be generic enough such that external (STELLAR) matches can be imported from a file)
2. generate possible complete bisulphite matches for each read
3. compute boundaries of methylation

A first step in the thesis should be an evaluation framework which can assess the quality of the solution for the developed algorithm and external tools. Simulated reads shall be generated by an extension of the Mason read simulator.

Literature

[1] Xi, Yuanxin, and Wei Li. 2009. “BSMAP: whole genome bisulfite sequence MAPping program..” BMC Bioinformatics 10: 232. doi:10.1186/1471-2105-10-232.

[2] Chen, Pao-Yang, Shawn J Cokus, and Matteo Pellegrini. 2010. “BS Seeker: precise mapping for bisulfite sequencing..” BMC Bioinformatics 11: 203. doi:10.1186/1471-2105-11-203.

[3] Lyko, Frank, Sylvain Foret, Robert Kucharski, Stephan Wolf, Cassandra Falckenhayn, and Ryszard Maleszka. 2010. “The Honey Bee Epigenomes: Differential Methylation of Brain DNA in Queens and Workers.” PLoS biology 8 (11): –. doi:10.1371/journal.pbio.1000506.

Work Plan

1. read literature (2 weeks)
2. develop model and optimization criteria for bisulphite treated reads (2 week)
3. extend Mason to generate bisulphite treated reads (4 weeks)
4. develop easy benchmark for bisulphite mapping (4 weeks)
5. implement bisulphite mapper (6 weeks)
6. program analsyis pipeline (1 weeks)
7. evaluate data (2 weeks)
8. write up thesis (3 weeks)