Identification, Review, and Systematic Cross-Validation of microRNA Prognostic Signatures in Metastatic Melanoma

In metastatic melanoma, it is vital to identify and validate biomarkers of prognosis. Previous studies have systematically evaluated protein biomarkers or mRNA-based expression signatures. No such analyses have been applied to microRNA (miRNA)-based prognostic signatures. As a first step, we identified two prognostic miRNA signatures from publicly available data sets (Gene Expression Omnibus/The Cancer Genome Atlas) of global miRNA expression profiling information. A 12-miRNA signature predicted longer survival after surgery for resection of American Joint Committee on Cancer stage III disease (>4 years, no sign of relapse) and outperformed American Joint Committee on Cancer standard-of-care prognostic markers in leave-one-out cross-validation analysis (error rates 34% and 38%, respectively). A similar 15-miRNA biomarker derived from The Cancer Genome Atlas miRNA-seq data performed slightly worse (39%) than these current biomarkers. Both signatures were then assessed for replication in two independent data sets and subjected to systematic cross-validation together with the three other miRNA-based prognostic signatures proposed in the literature to date. Five miRNAs (miR-142-5p, miR-150-5p, miR-342-3p, miR-155-5p, and miR-146b-5p) were reproducibly associated with patient outcome and have the greatest potential for application in the clinic. Our extensive validation approach highlighted among multiple independent cohorts the translational potential and limitations of miRNA signatures, and pointed to future directions in the analysis of this emerging class of markers

Directive 02-14: Tax Obligations of Persons Purchasing Cigarettes in Interstate Commerce for which the Massachusetts Cigarette Excise Has Not Been Paid

The development of accurate clinical biomarkers has been challenging in part due to the diversity between patients and diseases. One approach to account for the diversity is to use multiple markers to classify patients, based on the concept that each individual marker contributes information from its respective subclass of patients. Here we present a new strategy for developing biomarker panels that accounts for completely distinct patient subclasses. Marker State Space (MSS) defines "marker states" based on all possible patterns of high and low values among a panel of markers. Each marker state is defined as either a case state or a control state, and a sample is classified as case or control based on the state it occupies. MSS was used to define multi-marker panels that were robust in cross validation and training-set/test-set analyses and that yielded similar classification accuracy to several other classification algorithms. A three-marker panel for discriminating pancreatic cancer patients from control subjects revealed subclasses of patients based on distinct marker states. MSS provides a straightforward approach for modeling highly divergent subclasses of patients, which may be adaptable for diverse applications.</p

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) Spectrographs

We describe the design and performance of the near-infrared (1.51--1.70 micron), fiber-fed, multi-object (300 fibers), high resolution (R = lambda/delta lambda ~ 22,500) spectrograph built for the Apache Point Observatory Galactic Evolution Experiment (APOGEE). APOGEE is a survey of ~ 10^5 red giant stars that systematically sampled all Milky Way populations (bulge, disk, and halo) to study the Galaxy's chemical and kinematical history. It was part of the Sloan Digital Sky Survey III (SDSS-III) from 2011 -- 2014 using the 2.5 m Sloan Foundation Telescope at Apache Point Observatory, New Mexico. The APOGEE-2 survey is now using the spectrograph as part of SDSS-IV, as well as a second spectrograph, a close copy of the first, operating at the 2.5 m du Pont Telescope at Las Campanas Observatory in Chile. Although several fiber-fed, multi-object, high resolution spectrographs have been built for visual wavelength spectroscopy, the APOGEE spectrograph is one of the first such instruments built for observations in the near-infrared. The instrument's successful development was enabled by several key innovations, including a "gang connector" to allow simultaneous connections of 300 fibers; hermetically sealed feedthroughs to allow fibers to pass through the cryostat wall continuously; the first cryogenically deployed mosaic volume phase holographic grating; and a large refractive camera that includes mono-crystalline silicon and fused silica elements with diameters as large as ~ 400 mm. This paper contains a comprehensive description of all aspects of the instrument including the fiber system, optics and opto-mechanics, detector arrays, mechanics and cryogenics, instrument control, calibration system, optical performance and stability, lessons learned, and design changes for the second instrument.Comment: 81 pages, 67 figures, PASP, accepte

Traditional Medicine: Past, present and future research and development prospects and integration in the National Health System of Cameroon

Traditional medicine refers to health practices, approaches, knowledge and beliefs incorporating plant, animal and mineral based medicines, spiritual therapies, manual techniques and exercises, applied singularly or in combination to treat, diagnose and prevent illnesses or maintain well-being. In the last decade traditional medicine has become very popular in Cameroon, partly due to the long unsustainable economic situation in the country. The high cost of drugs and increase in drug resistance to common diseases like malaria, bacteria infections and other sexually transmitted diseases has caused the therapeutic approach to alternative traditional medicine as an option for concerted search for new chemical entities (NCE). The World Health Organisation (WHO) in collaboration with the Cameroon Government has put in place a strategic platform for the practice and development of TM in Cameroon. This platform aims at harmonizing the traditional medicine practice in the country, create a synergy between TM and modern medicine and to institutionalize a more harmonized integrated TM practices by the year 2012 in Cameroon. An overview of the practice of TM past, present and future perspectives that underpins the role in sustainable poverty alleviation has been discussed. This study gives an insight into the  strategic plan and road map set up by the Government of Cameroon for the organisational framework and research platform for the practice and development of TM, and the global partnership involving the management of TM in the country.Key words: Tradttional medicine, Cameroon

Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing

Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients to understand the range of aberrations that are occurring in each tumor. Because our understanding of PAC tumorigenesis is limited, evaluation of separate cases may reveal aberrations, that are less common but may provide relevant information on the disease, or that may represent viable therapeutic targets for the patient. We used next generation sequencing to assess global somatic events across 3 PAC patients to characterize each patient and to identify potential targets. This study is the first to report whole genome sequencing (WGS) findings in paired tumor/normal samples collected from 3 separate PAC patients. We generated on average 132 billion mappable bases across all patients using WGS, and identified 142 somatic coding events including point mutations, insertion/deletions, and chromosomal copy number variants. We did not identify any significant somatic translocation events. We also performed RNA sequencing on 2 of these patients' tumors for which tumor RNA was available to evaluate expression changes that may be associated with somatic events, and generated over 100 million mapped reads for each patient. We further performed pathway analysis of all sequencing data to identify processes that may be the most heavily impacted from somatic and expression alterations. As expected, the KRAS signaling pathway was the most heavily impacted pathway (P<0.05), along with tumor-stroma interactions and tumor suppressive pathways. While sequencing of more patients is needed, the high resolution genomic and transcriptomic information we have acquired here provides valuable information on the molecular composition of PAC and helps to establish a foundation for improved therapeutic selection

GReEn: a tool for efficient compression of genome resequencing data

Research in the genomic sciences is confronted with the volume of sequencing and resequencing data increasing at a higher pace than that of data storage and communication resources, shifting a significant part of research budgets from the sequencing component of a project to the computational one. Hence, being able to efficiently store sequencing and resequencing data is a problem of paramount importance. In this article, we describe GReEn (Genome Resequencing Encoding), a tool for compressing genome resequencing data using a reference genome sequence. It overcomes some drawbacks of the recently proposed tool GRS, namely, the possibility of compressing sequences that cannot be handled by GRS, faster running times and compression gains of over 100-fold for some sequences. This tool is freely available for non-commercial use at ftp://ftp.ieeta.pt/∼ap/codecs/GReEn1.tar.gz