Comparing Multi-objective and Threshold-moving ROC Curve Generation for a Prototype-based Classifier

Proceedings of: GECCO 2013: 15th International Conference on Genetic and Evolutionary Computation Conference (Amsterdam, The Netherlands, July 06-10, 2013): a recombination of the 22nd International Conference on Genetic Algorithms (ICGA) and the 18th Annual Genetic Programming Conference (GP), Amsterdam, The Netherlands, July 06-10, 2013Receiver Operating Characteristics (ROC) curves represent the performance of a classifier for all possible operating con-ditions, i.e., for all preferences regarding the tradeoff be-tween false positives and false negatives. The generation of a ROC curve generally involves the training of a single classifier for a given set of operating conditions, with the subsequent use of threshold-moving to obtain a complete ROC curve. Recent work has shown that the generation of ROC curves may also be formulated as a multi-objective optimization problem in ROC space: the goals to be min-imized are the false positive and false negative rates. This technique also produces a single ROC curve, but the curve may derive from operating points for a number of different classifiers. This paper aims to provide an empirical compar-ison of the performance of both of the above approaches, for the specific case of prototype-based classifiers. Results on synthetic and real domains shows a performance advantage for the multi-objective approach.GECCO 2013 Presentation slidesThis work has been funded by the Spanish Ministry of Science under contract TIN2011-28336 (MOVES project)En prens

MUSCLE : automated multi-objective evolutionary optimization of targeted LC-MS/MS analysis:Automated multi-objective evolutionary optimization of targeted LC-MS/MS analysis

Summary: Developing liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of (bio)chemicals is both time consuming and challenging, largely because of the large number of LC and MS instrument parameters that need to be optimized. This bottleneck significantly impedes our ability to establish new (bio)analytical methods in fields such as pharmacology, metabolomics and pesticide research. We report the development of a multi-platform, user-friendly software tool MUSCLE (multi-platform unbiased optimization of spectrometry via closed-loop experimentation) for the robust and fully automated multi-objective optimization of targeted LC-MS/MS analysis. MUSCLE shortened the analysis times and increased the analytical sensitivities of targeted metabolite analysis, which was demonstrated on two different manufacturer’s LC-MS/MS instruments. Availability and implementation: Available at http://www.muscleproject.org. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice

SummaryWe recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation. These effects were consistent in 3T3-L1 adipocytes, C2C12 myoblasts, and in tissues from Nat1-deficient mice, including white adipose tissue, heart, and skeletal muscle. Nat1-deficient mice had changes in plasma metabolites and lipids consistent with a decreased ability to utilize fats for energy and a decrease in basal metabolic rate and exercise capacity without altered thermogenesis. Collectively, our results suggest that Nat1 deficiency results in mitochondrial dysfunction, which may constitute a mechanistic link between this gene and IR

Predictive network modeling in human induced pluripotent stem cells identifies key driver genes for insulin responsiveness.

Insulin resistance (IR) precedes the development of type 2 diabetes (T2D) and increases cardiovascular disease risk. Although genome wide association studies (GWAS) have uncovered new loci associated with T2D, their contribution to explain the mechanisms leading to decreased insulin sensitivity has been very limited. Thus, new approaches are necessary to explore the genetic architecture of insulin resistance. To that end, we generated an iPSC library across the spectrum of insulin sensitivity in humans. RNA-seq based analysis of 310 induced pluripotent stem cell (iPSC) clones derived from 100 individuals allowed us to identify differentially expressed genes between insulin resistant and sensitive iPSC lines. Analysis of the co-expression architecture uncovered several insulin sensitivity-relevant gene sub-networks, and predictive network modeling identified a set of key driver genes that regulate these co-expression modules. Functional validation in human adipocytes and skeletal muscle cells (SKMCs) confirmed the relevance of the key driver candidate genes for insulin responsiveness

Stony coral tissue loss disease: a review of emergence, impacts, etiology, diagnostics, and intervention

Stony coral tissue loss disease (SCTLD) is destructive and poses a significant threat to Caribbean coral reef ecosystems. Characterized by the acute loss of coral tissue, SCTLD has impacted over 22 stony coral species across the Caribbean region, leading to visible declines in reef health. Based on the duration, lethality, host range, and spread of this disease, SCTLD is considered the most devastating coral disease outbreak ever recorded. Researchers are actively investigating the cause and transmission of SCTLD, but the exact mechanisms, triggers, and etiological agent(s) remain elusive. If left unchecked, SCTLD could have profound implications for the health and resilience of coral reefs worldwide. To summarize what is known about this disease and identify potential knowledge gaps, this review provides a holistic overview of SCTLD research, including species susceptibility, disease transmission, ecological impacts, etiology, diagnostic tools, host defense mechanisms, and treatments. Additionally, future research avenues are highlighted, which are also relevant for other coral diseases. As SCTLD continues to spread, collaborative efforts are necessary to develop effective strategies for mitigating its impacts on critical coral reef ecosystems. These collaborative efforts need to include researchers from diverse backgrounds and underrepresented groups to provide additional perspectives for a disease that requires creative and urgent solutions