bioRxiv Science⌕ Search

Biology subjects

Jandrasits, C.

Publications and source records attributed to Jandrasits, C..

3 recordsLinked to original sources

Improving tuberculosis surveillance by detecting international transmission using publicly available whole-genome sequencing data

IntroductionImproving the surveillance of tuberculosis (TB) is especially important for multidrug-resistant (MDR) and extensively drug-resistant (XDR)-TB. The large amount of publicly available whole-genome sequencing (WGS) data for TB gives us the chance to re-use data and to perform additional analysis at a large scale. AimWe assessed the usefulness of raw WGS data of global MDR/XDR-TB isolates available from public repositories to improve TB surveillance. MethodsWe extracted raw WGS data and the related metadata of Mycobacterium tuberculosis isolates available from the Sequence Read Archive. We compared this public dataset with WGS data and metadata of 131 MDR- and XDR-TB isolates from Germany in 2012-2013. ResultsWe aggregated a dataset that includes 1,081 MDR and 250 XDR isolates among which we identified 133 molecular clusters. In 16 clusters, the isolates were from at least two different countries. For example, cluster2 included 56 MDR/XDR isolates from Moldova, Georgia, and Germany. By comparing the WGS data from Germany and the public dataset, we found that 11 clusters contained at least one isolate from Germany and at least one isolate from another country. We could, therefore, connect TB cases despite missing epidemiological information. ConclusionWe demonstrated the added value of using WGS raw data from public repositories to contribute to TB surveillance. By comparing the German and the public dataset, we identified potential international transmission events. Thus, using this approach might support the interpretation of national surveillance results in an international context.

microbiology↗

Computational Pan-genome Mapping and pairwise SNP-distance improve Detection of Mycobacterium tuberculosis Transmission Clusters

Next-generation sequencing based base-by-base distance measures have become an integral complement to epidemiological investigation of infectious disease outbreaks. This study introduces PANPASCO, a computational pan-genome mapping based, pairwise distance method that is highly sensitive to differences between cases, even when located in regions of lineage specific reference genomes. We show that our approach is superior to previously published methods in several datasets and across different Mycobacterium tuberculosis lineages, as its characteristics allow the comparison of a high number of diverse samples in one analysis - a scenario that becomes more and more likely with the increased usage of whole-genome sequencing in transmission surveillance.\n\nAuthor summaryTuberculosis still is a threat to global health. It is essential to detect and interrupt transmissions to stop the spread of this infectious disease. With the rising use of next-generation sequencing methods, its application in the surveillance of Mycobacterium tuberculosis has become increasingly important in the last years. The main goal of molecular surveillance is the identification of patient-patient transmission and cluster detection. The mutation rate of M. tuberculosis is very low and stable. Therefore, many existing methods for comparative analysis of isolates provide inadequate results since their resolution is too limited. There is a need for a method that takes every detectable difference into account. We developed PANPASCO, a novel approach for comparing pairs of isolates using all genomic information available for each pair. We combine improved SNP-distance calculation with the use of a pan-genome incorporating more than 100 M. tuberculosis reference genomes for read mapping prior to variant detection. We thereby enable the collective analysis and comparison of similar and diverse isolates associated with different M. tuberculosis strains.

bioinformatics↗

seq-seq-pan: Building a computational pan-genome data structure on whole genome alignment

BackgroundThe increasing application of next generation sequencing technologies has led to the availability of thousands of reference genomes, often providing multiple genomes for the same or closely related species. The current approach to represent a species or a population with a single reference sequence and a set of variations cannot represent their full diversity and introduces bias towards the chosen reference. There is a need for the representation of multiple sequences in a composite way that is compatible with existing data sources for annotation and suitable for established sequence analysis methods. At the same time, this representation needs to be easily accessible and extendable to account for the constant change of available genomes.\n\nResultsWe introduce seq-seq-pan, a framework that provides methods for adding or removing new genomes from a set of aligned genomes and uses these to construct a whole genome alignment. Throughout the sequential workflow the alignment is optimized for generating a representative linear presentation of the aligned set of genomes, that enables its usage for annotation and in downstream analyses.\n\nConclusionsBy providing dynamic updates and optimized processing, our approach enables the usage of whole genome alignment in the field of pan-genomics. In addition, the sequential workflow can be used as a fast alternative to existing whole genome aligners. seq-seq-pan is freely available at https://gitlab.com/groups/rki_bioinformatics

bioinformatics↗