Genetic Signatures of Drug Response Variability in Drosophila melanogaster.

Knowledge of the genetic basis underlying variation in response to environmental exposures or treatments is important in many research areas. For example, knowing the set of causal genetic variants for drug responses could revolutionize personalized medicine. We used Drosophila melanogaster to investigate the genetic signature underlying behavioral variability in response to methylphenidate (MPH), a drug used in the treatment of attention-deficit/hyperactivity disorder. We exposed a wild-type D. melanogaster population to MPH and a control treatment, and observed an increase in locomotor activity in MPH-exposed individuals. Whole-genome transcriptomic analyses revealed that the behavioral response to MPH was associated with abundant gene expression alterations. To confirm these patterns in a different genetic background and to further advance knowledge on the genetic signature of drug response variability, we used a system of inbred lines, the Drosophila Genetic Reference Panel (DGRP). Based on the DGRP, we showed that the behavioral response to MPH was strongly genotype-dependent. Using an integrative genomic approach, we incorporated known gene interactions into the genomic analyses of the DGRP, and identified putative candidate genes for variability in drug response. We successfully validated 71% of the investigated candidate genes by gene expression knockdown. Furthermore, we showed that MPH has cross-generational behavioral and transcriptomic effects. Our findings establish a foundation for understanding the genetic mechanisms driving genotype-specific responses to medical treatment, and highlight the opportunities that integrative genomic approaches have in optimizing medical treatment of complex diseases.

The fungal community changes over time in developing wheat heads.

Under normal conditions, wheat is colonized by a multitude of fungi that can have beneficial or adverse effects on plant growth and yield. To study the effect of spraying wheat heads with fungicides on the fungal community from emergence to harvest we applied an amplicon sequencing approach on single wheat heads. The climatic data showed that the spring of 2014 was very dry and without precipitation in the two weeks around flowering. An initial quantitative PCR showed that the total amount of fungal DNA increased during the entire period, without significant difference between sprayed and control wheat heads. Amplicon sequencing of the internal transcribed spacer 2 (ITS2) region showed that operational taxonomic units (OTUs) identified as Sporobolomyces roseus dominated in the first weeks, whereas Alternaria infectoria OTUs dominated in the last weeks before harvest. The only observed significant difference was that the control wheat heads contained more of the powdery mildew causing Blumeria graminis f. sp. tritici OTUs compared with the sprayed wheat heads. The dry conditions around flowering most likely also had an effect on Fusarium head blight infection as Fusarium OTUs were only sporadically encountered. Analyses of secondary metabolites produced by Fusarium and Alternaria in the wheat heads confirmed the observations from the amplicon sequencing. Enniatin B was the most frequent contaminant present in four sprayed (49-538 ng/g) and three control (56-355 ng/g) wheat heads. The A. infectoria secondary metabolites infectopyrone and 4Z-infectopyrone were however consistently observed in all samples collected the last five weeks before harvest.