Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

Fuzzy Model for Quantitative Assessment of Environmental Start-up Projects in Air Transport.

The purpose of this paper is to develop an applied fuzzy model of information technology to obtain quantitative estimates of environmental start-up projects in air transport. The developed model will become a useful tool for venture funds, business angels, or crowdfunding platforms for the development of innovative air transport businesses. Obtaining a quantitative estimate of the environmental start-up projects will increase the sustainability of the decision making on the security of financing of such projects by investors. This article develops a fuzzy evaluation model of project start-ups in air transport as an application of our neuro-fuzzy model in a specific air transport environment. The applied model provides output ranking of start-up project teams in air transport based on a four-layer neuro-fuzzy network. The presented model declares the possibilities of the application to solve these economic problems and offers the space for subsequent research focused on its usability in several areas of start-up development, in sectors and processes differentiated. The benefits are also visible for several types of policies, with an emphasis on decision-making processes in regulatory mechanisms to support the state funding in Slovakia, the EU etc.

Treatments for mild-to-moderate recalcitrant plaque psoriasis: expected clinical and economic outcomes for first-line and second-line care.

The cost effectiveness of treatments for psoriasis has been evaluated previously by several different investigators. Such evaluations should be updated as new products or data become available. To this end, a comparison of expected treatment-related clinical and economic outcomes is undertaken from the payer perspective using a disease-intervention model, decision analyses, and newly emergent information. The model is based on academy guidelines and recommended clinical practice. Model inputs (clinical and cost data) are culled from the medical literature and advisory clinical assessment surveys. Comparable therapies are various topical pharmacotherapies and phototherapies, including the 308-nm excimer laser (XTRAC, PhotoMedex, Montgomeryville, PA). Analytic results indicate that clinical and economic outcomes are influenced by treatment selections but are muted by the rotational nature of treatment regimens. Multiple analyses are required to reveal individual product performance. On the basis of these analyses, the addition of the 308-nm excimer laser to the rotational mix of treatments commonly utilized as second-line therapies for mild-to-moderate plaque psoriasis is expected to add incremental clinical benefit for patients without incremental cost for payers, because the laser can replace both more costly and less costly alternatives for appropriately selected patients who require a different therapeutic modality to maintain or improve their responsiveness.

Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing.

As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95-99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.

Initial sequencing and comparative analysis of the mouse genome.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.