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

Strategic Technology Investments in Open Economies

We study a general equilibrium model of international trade with heterogeneous firms, where countries can strategically invest in technology. The countries' motive is to improve firms' productivity, leading to a competitive advantage in international trade. We are interested in how trade liberalization affects this governmental incentive to invest in technology. In the closed economy countries invest if consumers have a sufficiently high preference for varieties. In the open economy we analyze the Nash-equilibrium policy and the cooperative policy. If there are no cross-country investment spillovers, countries strategically compete in their investment levels and increase their investments with higher trade openness. From a social perspective we have an overinvestment problem. If there are cross-country investment spillovers, we differentiate between weak and strong spillovers. In both cases the cooperative solution predicts a positive relationship between investments and trade openness. If there are weak (strong) spillovers, we find a positive (hump-shaped) relationship between technology investments and trade openness in the Nash-equilibrium. From a social perspective we obtain an over (under)-investment problem if spillovers are weak (strong).Der Artikel untersucht strategische Technologieinvestitionen in einem allgemeinen Gleichgewichtsmodell mit heterogenen Firmen. Länder haben die Möglichkeit, durch Technologieinvestitionen die Produktivität ihrer Firmen zu verbessern und ihnen somit einen Konkurrenzvorteil im internationalen Wettbewerb zu geben. In diesem Modellrahmen betrachten wir den Einfluss von Handelsliberalisierung auf den Anreiz in Technologie zu investieren. In geschlossenen Volkswirtschaften investieren Länder dann, wenn Konsumenten eine ausreichend starke Präferenz für Varietäten aufweisen. In der offenen Volkswirtschaft untersuchen wir das Nash-Gleichgewicht sowie die kooperative Lösung. Ohne Spillover-Effekte durch Technologieinvestitionen auf ein anderes Land, erhöhen Länder ihre Investitionsniveaus strategisch mit zunehmender Handelsoffenheit. Dies führt zu, aus wohlfahrtstheoretischer Perspektive, zu hohen Investitionen. Werden länderübergreifende Spillover-Effekte angenommen, so dass ein Land von den Investitionen eines anderen Landes profitiert, differenzieren wir zwischen einem schwachen und einem starken Spillover. In beiden Szenarien ist in der kooperativen Lösung ein positiver Zusammenhang zwischen Handelsliberalisierung und Investitionen zu beobachten. Im Nash-Gleichgewicht beobachten wir im Fall von einem schwachen (starken) Spillover einen positiven (u-förmigen) Zusammenhang zwischen Technologieinvestitionen und zunehmender Handelsoffenheit. Aus wohlfahrtstheoretischer Perspektive weist dieses Szenario ein zu hohes (zu niedriges) Investitionsvolumen auf