Learning and development of pipelines for processing and analysis of new generation sequencing data, which enable data wrangling and improved efficiency of identification of new antimicrobial substances and quantification of presence and mobility of antimicrobial resistance.
F.01 Acquisition of new practical knowledge, information and skills
COBISS.SI-ID: 1540168900FEMS 2017 Poster Award: Due to the increasing problem of antimicrobial resistance, modeling and analysis of horizontal gene transfer processes is an essential research area. We focus on the most widespread and damaging of these processes, conjugation, where transfer of plasmids between different microbial hosts allows the storage and transfer of resistance genes. I will present a new approach to analysis of plasmids based on interpreting the origin-of-transfer, a merely 200 bp long non-coding plasmid DNA region that is the enzymatic substrate for the relaxase. Using a statistical approach we have only recently verified that these enzymatic DNA substrates contain conserved structural properties in relation to groups of conserved relaxases, and that computational DNA structure prediction much more accurately distinguishes substrate properties than analysis of nucleotide sequences. Therefore, using a newly developed structural representation of DNA and bioinformatic algorithm, we develop a tool to determine the mobility of plasmids, which can predict even the range of potential plasmid hosts. Our algorithm has proved so effective, that it can uncover new DNA substrates, and we have identified hundreds of new plasmid transfer regions based on an initial set of 64 experimentally determined ones. Our tools for prediction of DNA structural properties and for determining the mobility and host range of plasmids were implemented as Web tools on the server http://dnatools.eu. We are also establishing a tool for structural alignment of DNA, which will allow characterization of a number of new DNA substrates that until now could not be detected using existing tools.
E.02 International awards
COBISS.SI-ID: 30703911The webtool for prediction of mobility of bacterial plasmids and their potential hosts. The tool is very useful for a wide degree of research fields, which include analysis of development of antimicrobial resistance. The report that describes development of the tool is in publishing process.
F.23 Development of new system-wide, normative and programme solutions, and methods
COBISS.SI-ID: 1539179972Matlab tools for analysis of plasmids.
F.23 Development of new system-wide, normative and programme solutions, and methods
COBISS.SI-ID: 1540184260Presentation at an annual symposium/meeting of a consortium of universities and experts in the field of analysis and prediction of structural properties of RNA and DNA molecules. Identification of regulatory regions in DNA is important for resolving biological processes. The representation of DNA molecules as strings of four letters, has in many cases been shown to be insufficient to describe protein binding features in regulatory regions and enable us to resolve the regions according to protein defined functional groups. A representation of DNA based on its conformational and physicochemical properties should therefore be tested and used in construction of algorithms for sorting and discovering regulatory regions. We applied our structural models and representations of DNA in a system of regions that regulate the transfer of bacterial plasmids. In this system, only about 60 such regions have been experimentally determined and sorted into 4 mobility groups defined by amino acid sequences of plasmid- encoded mobilization proteins. However, many more plasmids that carry such regulatory regions have been sequenced, and in light of the rising threat of antimicrobial resistance facilitated by horizontal gene transfer of plasmids, it is important to be able to quickly determine plasmid mobility by characterizing the regulatory regions. To facilitate characterization of regulatory regions and mobility groups, we developed bioinformatic procedures based on structural representations of DNA and a dynamic programming algorithm. The properties of the new representations and algorithm were tested and fine tuned using statistical procedures. Using the procedures, we discovered new regulatory regions in hundreds of plasmids and mobile elements. We statistically confirmed that DNA structural properties in regulatory regions are highly conserved in the mobility groups, much more in fact than nucleotide sequences. Therefore, the structural representation can be used to discriminate among the groups more efficiently than by using nucleotide sequences. Consequently, plasmid mobility groups can now be resolved with almost perfect accuracy, and procedures for prediction of plasmid MOB groups were implemented in a web-tool available at http://www.dnatools.eu.
B.06 Other
COBISS.SI-ID: 1539179716