Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach

Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors

Particle identification in ALICE : a Bayesian approach

Peer reviewe

The external micro-anatomy of the cephalon of the asellotan isopod Craseriella anops

The micro-anatomy of the cephalon is described in the troglobic asellotan isopod Craseriella anops from the Nohoch Nah Chich anchialine cave system in southeast Mexico. The cephalon is entirely covered by cuticular scales bordered by marginal spines. The anterior end of the cephalon is bordered by a carina that is wider medially. The isopod is eyeless. The distal seventh portion of the cephalon is characterized by the presence of two sutures and six setae. A suture is found on each side of the distal margin of the cephalon. Each suture is bordered by microtrichs. Two simple setae with a sensory hair, articulated on the base by a socket, are found one on each side of each of the sutures. Two additional setae, similar in shape and size, occur medially on the cephalon. A terminal pore is absent on the sensory hairs of all setae. These setae are suggested to be mechanoreceptors that provide directional sensitivity and enhance the sensibility of turbulent motion, viscosity and changes of hydrostatic pressure

Outcome predictors for status epilepticus-what really counts

In adult patients with status epilepticus (SE)-a life-threatening state of ongoing or repetitive seizures-the current evidence regarding outcome prediction is based on clinical, biochemical and EEG determinants. These predictors of outcome involve clinical features such as age, history of prior seizures or epilepsy, SE aetiology, level of consciousness, and seizure type at SE onset. The clinical risk-benefit calculation between the danger of undertreated persistent seizure activity and, conversely, the potential damage from unwarranted aggressive treatments remains a constant challenge. Improved knowledge of outcome determinants, as well as increased availability of reliable outcome prediction models early in the course of SE, is paramount for optimization of treatment of patients who develop this disorder. In this Review, we discuss the major prognostic determinants of outcome in SE. Through consideration of studies that provide measures of association between predictors of SE outcome and death, we propose a detailed-but as yet unvalidated-paradigm for assessment of these predictors during the course of SE. Such an algorithm could guide the organization of results from existing trials and provide direction with regard to the parameters that should be monitored in future studies of SE