CACHE (Critical Assessment of Computational Hit-finding Experiments): A public–private partnership benchmarking initiative to enable the development of computational methods for hit-finding

One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small-molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small-molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared and openly published. CACHE will launch three new benchmarking exercises every year. The outcomes will be better prediction methods, new small-molecule binders for target proteins of importance for fundamental biology or drug discovery and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins. [Figure not available: see fulltext.

Stakeholders' perspectives on the regulation and integration of complementary and alternative medicine products in Lebanon: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The regulation of the markets for Complementary and Alternative Medicine (CAM) products presents a global challenge. There is a dearth of studies that have examined or evaluated the regulatory policies of CAM products in the Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and the barriers for the proper regulation and integration of CAM products in Lebanon, as an example of an EMR country with a weak public infrastructure.</p> <p>Methods</p> <p>We utilized a qualitative study design involving a series of semi-structured interviews with stakeholders of the CAM market in Lebanon. Snowball sampling was used to identify interviewees; interviews continued until the "saturation" point was reached. A total of 16 interviews were carried out with decision makers, representatives of professional associations, academic researchers, CAM product importers, policy makers and a media representative. Interviews were transcribed and thematic analysis of scripts was carried out.</p> <p>Results</p> <p>There was a consensus among all stakeholders that the regulation of the market for CAM products in Lebanon needs to be strengthened. Thematic analysis identified a number of impediments jeopardizing the safety of public consumption and hindering the integration of CAM therapies into mainstream medicine; including: weak infrastructure, poor regulation, ineffective policies and politics, weak CAM awareness and sub-optimal coordination and cooperation among stakeholders. With respect to policy instruments, voluntary instruments (self regulation) were deemed ineffective by stakeholders due to poor awareness of both users and providers on safe use of CAM products. Stakeholders' rather recommended the adoption of a combination of mixed (enhancing public awareness and integration of CAM into medical and nursing curricula) and compulsory (stricter governmental regulation) policy instruments for the regulation of the market for CAM products.</p> <p>Conclusions</p> <p>The current status quo with respect to the regulation of CAM products in Lebanon is not conducive to public safety, nor does it support the integration of CAM products into the healthcare system. The Ministry of Health indeed plays a dominant role in the regulation of these products through a combination of mixed and compulsory policy instruments. Yet, the proper implementation of these regulations requires political resolve coupled with the cooperation of all CAM stakeholders.</p

Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations

To investigate the regulation of seed metabolism and to estimate the degree of metabolic natural variability, metabolite profiling and network analysis were applied to a collection of 76 different homozygous tomato introgression lines (ILs) grown in the field in two consecutive harvest seasons. Factorial ANOVA confirmed the presence of 30 metabolite quantitative trait loci (mQTL). Amino acid contents displayed a high degree of variability across the population, with similar patterns across the two seasons, while sugars exhibited significant seasonal fluctuations. Upon integration of data for tomato pericarp metabolite profiling, factorial ANOVA identified the main factor for metabolic polymorphism to be the genotypic background rather than the environment or the tissue. Analysis of the coefficient of variance indicated greater phenotypic plasticity in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability suggested that the mode of inheritance of metabolite traits in the seed differed from that in the fruit. Correlation-based metabolic network analysis comparing metabolite data for the seed with that for the pericarp showed that the seed network displayed tighter interdependence of metabolic processes than the fruit. Amino acids in the seed metabolic network were shown to play a central hub-like role in the topology of the network, maintaining high interactions with other metabolite categories, i.e., sugars and organic acids. Network analysis identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile, Val, and Pro. The strong interdependence of this group was confirmed by the mQTL mapping. Taken together these results (i) reflect the extensive redundancy of the regulation underlying seed metabolism, (ii) demonstrate the tight co-ordination of seed metabolism with respect to fruit metabolism, and (iii) emphasize the centrality of the amino acid module in the seed metabolic network. Finally, the study highlights the added value of integrating metabolic network analysis with mQTL mapping

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome