The Department for “Computational Biology of Infection Research“ at HZI offers a Bachelor- /Master-Project on the field of “Metagenomics Research”. We are looking for highly motivated students of bioinformatics, computer science or similar to work on the problems outlined below.
Conjugation, the interbacterial transmission of circular DNA, is an biologically important and highly efficient mechanism for the horizontal spread of genes, allowing cells to adapt to different environments, for example by the uptake of antibiotic resistance genes (ABR). Plasmids and conjugative transposons harbor an immense repertoire of ABR genes and thus play a central role in the maintenance and spread of ABRs in bacterial communities.
Several culture-independent techniques have been developed to obtain insights into the plasmid diversity in metagenomics samples. These methods are based on physical segregation of plasmid and chromosomal DNA, which is costly and only applicable to new experiments. Therefore, the aims of your project are: (1) the development of a reference-based plasmid assembler and (2) the comparison with optimized de novo plasmid assembly techniques.
1. Marker gene-based plasmid assembly
· Generation of a phylogenetic tree using a fast maximum-likelihood method of all publicly available plasmid sequences,
· Identification of highly conserved proteins, shared between the majority of plasmids within one clade, to use as marker genes,
· Plasmid assembly using bait- or mapping-based techniques, using the identified marker genes as recruitment seeds,
· Automatic gene annotation of reconstructed plasmid sequences and subsequent assembly visualization.
2. Bayesian optimization of de novo assembly techniques
· Generation of test datasets for the optimization process.
· Development of an evaluation method (e.g. assembly score in respect to circularity, mapping identity to a curated plasmid database),
· Optimization of hyperparameters of assembly tools in respect to the evaluation score using Bayesian optimization techniques,
· Validation and application of optimized assembly technique to large-scale datasets and comparison to the reference-based plasmid assembly strategy outlined in (1).
- Bioinformatik der Infektionsforschung - Prof. Dr. Alice McHardy