ABSTRACT
Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to a broad community, we implemeted VarCap on a Galaxy webserver, which is accessible at http://galaxy.csb.univie.ac.at.
ABSTRACT
BACKGROUND: Wikipedia is an important source of medical information for both patients and medical professionals. Given its wide reach, improving the quality, completeness, and accessibility of medical information on Wikipedia could have a positive impact on global health. OBJECTIVE: We created a prototypical implementation of an automated system for keeping drug-drug interaction (DDI) information in Wikipedia up to date with current evidence about clinically significant drug interactions. Our work is based on Wikidata, a novel, graph-based database backend of Wikipedia currently in development. METHODS: We set up an automated process for integrating data from the Office of the National Coordinator for Health Information Technology (ONC) high priority DDI list into Wikidata. We set up exemplary implementations demonstrating how the DDI data we introduced into Wikidata could be displayed in Wikipedia articles in diverse languages. Finally, we conducted a pilot analysis to explore if adding the ONC high priority data would substantially enhance the information currently available on Wikipedia. RESULTS: We derived 1150 unique interactions from the ONC high priority list. Integration of the potential DDI data from Wikidata into Wikipedia articles proved to be straightforward and yielded useful results. We found that even though the majority of current English Wikipedia articles about pharmaceuticals contained sections detailing contraindications, only a small fraction of articles explicitly mentioned interaction partners from the ONC high priority list. For 91.30% (1050/1150) of the interaction pairs we tested, none of the 2 articles corresponding to the interacting substances explicitly mentioned the interaction partner. For 7.21% (83/1150) of the pairs, only 1 of the 2 associated Wikipedia articles mentioned the interaction partner; for only 1.48% (17/1150) of the pairs, both articles contained explicit mentions of the interaction partner. CONCLUSIONS: Our prototype demonstrated that automated updating of medical content in Wikipedia through Wikidata is a viable option, albeit further refinements and community-wide consensus building are required before integration into public Wikipedia is possible. A long-term endeavor to improve the medical information in Wikipedia through structured data representation and automated workflows might lead to a significant improvement of the quality of medical information in one of the world's most popular Web resources.
