deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes

Superior removal of humic acid from aqueous stream using novel calf bones charcoal nanoadsorbent in a reversible process

While the potable water disinfection regimen has significantly reduced waterborne diseases, development of disinfection byproducts (DBP) during this process has brought a global threat to the environment and human health. The most notorious water pollutant, humic acid (HA), transforms into carcinogenic byproducts during the disinfection process (chlorination) of water treatment. HA removal methods are neither economic nor widely available. This study addresses the most urgent global issue of HA removal by developing an innovative and self-regenerative process based on a low-cost and self-regenerative calf bone char (CBC) that removed 92.1–100% of HA. CBC-based HA removal has not been described yet. The developed CBC, as a super adsorbent of HA, was initially characterized by a scanning electron microscope. Various parameters of adsorption/desorption and self-regeneration of CBC adsorbent were experimentally determined. Results show that prepared CBC with a 112 m2/g surface area exhibited adsorption of 38.08 mg/g (HA = 20 mg/L, pH = 4.0) which is several folds higher than the typical amount of HA present in water. The 30 m reaction time was enough to remove HA which is the shorter HA time in comparison to other similar studies. The increase of HA from 0.5 to 5 g/L, raises % HA removal (36.7–99.8%) while a pH decrease (10–4) increases adsorption (12.3–98.3%). The adsorption data fitted well with the pseudo-second-order model and the Langmuir isotherm which demonstrate that adsorption takes place by a monolayer formation. Thermodynamic constants supported the endothermic, spontaneous and reversible nature of adsorption which can attain 100% HA removal. 100% regeneration of exhausted CBC by NaOH further supports the sustainability of the process. CBC as a new adsorbent material thus provides an economical and sustainable water pre-treatment procedure. The present study provides technical guidance for building a cost-effective and scalable process capable of providing clean water

Evidence-based and heuristic approaches for customization of care in cardiometabolic syndrome after spinal cord injury

Component and coalesced health risks of the cardiometabolic syndrome (CMS) are commonly reported in persons with spinal cord injuries (SCIs). These CMS hazards are also co-morbid with physical deconditioning and elevated pro-atherogenic inflammatory cytokines, both of which are common after SCI and worsen the prognosis for all-cause cardiovascular disease. This article describes a systematic procedure for individualized CMS risk assessment after SCI, and emphasizes evidence-based and intuition-centered countermeasures to disease. A unified approach will propose therapeutic lifestyle intervention as a routine plan for aggressive primary prevention in this risk-susceptible population. Customization of dietary and exercise plans then follow, identifying shortfalls in diet and activity patterns, and ways in which these healthy lifestyles can be more substantially embraced by both stakeholders with SCI and their health care providers. In cases where lifestyle intervention utilizing diet and exercise is unsuccessful in countering risks, available pharmacotherapies and a preferred therapeutic agent are proposed according to authoritative standards. The over-arching purpose of the monograph is to create an operational framework in which existing evidence-based approaches or heuristic modeling becomes best practice. In this way persons with SCI can lead more active and healthy lives