Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer

BACKGROUND: The recurrence and non-random distribution of translocation breakpoints in human tumors are usually attributed to local sequence features present in the vicinity of the breakpoints. However, it has also been suggested that functional constraints might contribute to delimit the position of translocation breakpoints within the genes involved, but a quantitative analysis of such contribution has been lacking. METHODOLOGY: We have analyzed two well-known signatures of functional selection, such as reading-frame compatibility and non-random combinations of protein domains, on an extensive dataset of fusion proteins resulting from chromosomal translocations in cancer. CONCLUSIONS: Our data provide strong experimental support for the concept that the position of translocation breakpoints in the genome of cancer cells is determined, to a large extent, by the need to combine certain protein domains and to keep an intact reading frame in fusion transcripts. Additionally, the information that we have assembled affords a global view of the oncogenic mechanisms and domain architectures that are used by fusion proteins. This can be used to assess the functional impact of novel chromosomal translocations and to predict the position of breakpoints in the genes involved

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

Enhancement of surface properties for coal beneficiation. Final report

This report will focus on means of pyrite removal from coal using surface-based coal cleaning technologies. The major subjects being addressed in this study are the natural and modulated surface properties of coal and pyrite and how they may best be utilized to facilitate their separation using advanced surface-based coal cleaning technology. Emphasis is based on modified flotation and oil agglomerative processes and the basic principles involved. The four areas being addressed are: (1) Collectorless flotation of pyrite; (2) Modulation of pyrite and coal hydrophobicity; (3) Emulsion processes and principles; (4) Evaluation of coal hydrophobicity

Effect of frother type in collectorless flotation of two high-rank coking coals of Gondwana origin

Two high-rank coking coals of drift origin, which exhibited strong natural hydrophobicity, were used in this work. As high as 64-74% yield could be achieved through collectorless batch flotation with three different frothers: pine oil, MIBC, and a synthetic frother for three different feed sizes. It appears that a fairly long wetting time minimized the frother consumption. The flotation response of three different sizes, -0.5 mm, -0.5+0.1 mm,and -0.1 mm of the same feed, was found to be different for the three frothers. Frother performance was also found to vary with the same size of the two coals. The performance of the synthetic frother and MIBC was found to be superior for the -0.5 + 0.1 mm and -0.1 mm feeds, respectively. MIBC performed best for the -0.5 mm feed of one coal, whereas the synthetic frother did the same for the other coal. Frother performance also seems to be dependent on performance evaluation methodology