Regulatory bioinformatics for food and drug safety.

"Regulatory Bioinformatics" strives to develop and implement a standardized and transparent bioinformatic framework to support the implementation of existing and emerging technologies in regulatory decision-making. It has great potential to improve public health through the development and use of clinically important medical products and tools to manage the safety of the food supply. However, the application of regulatory bioinformatics also poses new challenges and requires new knowledge and skill sets. In the latest Global Coalition on Regulatory Science Research (GCRSR) governed conference, Global Summit on Regulatory Science (GSRS2015), regulatory bioinformatics principles were presented with respect to global trends, initiatives and case studies. The discussion revealed that datasets, analytical tools, skills and expertise are rapidly developing, in many cases via large international collaborative consortia. It also revealed that significant research is still required to realize the potential applications of regulatory bioinformatics. While there is significant excitement in the possibilities offered by precision medicine to enhance treatments of serious and/or complex diseases, there is a clear need for further development of mechanisms to securely store, curate and share data, integrate databases, and standardized quality control and data analysis procedures. A greater understanding of the biological significance of the data is also required to fully exploit vast datasets that are becoming available. The application of bioinformatics in the microbiological risk analysis paradigm is delivering clear benefits both for the investigation of food borne pathogens and for decision making on clinically important treatments. It is recognized that regulatory bioinformatics will have many beneficial applications by ensuring high quality data, validated tools and standardized processes, which will help inform the regulatory science community of the requirements necessary to ensure the safe introduction and effective use of these applications.

Nucleotide polymorphism in the Est6 promoter, which is widespread in derived populations of Drosophila melanogaster, changes the level of Esterase 6 expressed in the male ejaculatory duct.

Previous analysis of an Australian population of D. melanogaster revealed two predominant Est6 promoter haplotypes, P1 and P7. These haplotypes, which differ at 14 sites over a 325-bp region, are associated with a 15-20% difference in male EST6 activity. Here we show that the P1/P7 sequence difference causes the male activity variation by recreating the activity difference among >60 independently transformed lines containing representative P1 or P7 promoter alleles fused to an identical Est6 coding region. Furthermore we find that the whole fly difference reflects about a twofold difference in EST6 activity in the anterior sperm ejaculatory duct. EST6 activity variation in this tissue is known to affect reproductive fitness. Using a combination of RFLP analysis and DNA sequencing, we show that P1 and P7 are predominant in six populations from America, Asia, and Australia, albeit less frequent in a population from the presumptively ancestral east African range of the species. The sequence data show significant departures from neutral expectations for the derived American and Australian populations but not the presumptively ancestral Zimbabwean population. Thus the P1/P7 difference could be a major source of adaptively significant EST6 activity variation through much of the now cosmopolitan range of D. melanogaster.