One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.
Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed “reads” are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions.
We introduce a framework for detecting driver mutations via functional network analysis, which is applied to individual genomes and does not require pooling multiple samples. It probabilistically evaluates 1) functional network links between different mutations in the same genome and 2) links between individual mutations and known cancer pathways. In addition, it can employ correlations of mutation patterns in pairs of genes. The method was used to analyze genomic alterations in two TCGA datasets, one for glioblastoma multiforme and another for ovarian carcinoma, which were generated using different approaches to mutation profiling. The proportions of drivers among the reported de novo point mutations in these cancers were estimated to be 57.8% and 16.8%, respectively. The both sets also included extended chromosomal regions with synchronous duplications or losses of multiple genes. We identified putative copy number driver events within many such segments. Finally, we summarized seemingly disparate mutations and discovered a functional network of collagen modifications in the glioblastoma. In order to select the most efficient network for use with this method, we used a novel, ROC curve-based procedure for benchmarking different network versions by their ability to recover pathway membership.CONCLUSIONS:
The results of our network-based procedure were in good agreement with published gold standard sets of cancer genes and were shown to complement and expand frequency-based driver analyses. On the other hand, three sequence-based methods applied to the same data yielded poor agreement with each other and with our results. We review the difference in driver proportions discovered by different sequencing approaches and discuss the functional roles of novel driver mutations. The software used in this work and the global network of functional couplings are publicly available at http://research.scilifelab.se/andrej_alexeyenko/downloads.html.
Original Russian thought came into existence fairly late - as late as the 18th and 19th centuries. Creating their own conceptions, Russian thinkers readily referred to various philosophical traditions: the Eastern Christian one as well as the schools and currents that emerged in the West. At the same time, one can observe a reverse phenomenon: Western intellectuals too - philosophers, theologians, men of letters - in one way or another would refer to the oeuvre by Russian writers. This process, which in its broadest sense can be described as the reception of Russian thought in the West (above all in Europe), was begun still in Vladimir Solovyov's lifetime (19th century) and has continued till this day. The notion of reception, employed in this publication, is quite broad in its sense. It means both the influence of Russian philosophy on the works by Western fellow writers, and the criticism and polemics undertaken by the latter, as well as the development, study and research into the thought created in the Russian milieu. All these aspects have come to be reflected in the book hereby presented for the Reader.
A paper is devoted to the project of annual international scientific and educational seminars on the philosophy of history “Eschatos”. The seminars are organized from 2010 by joint forces of scholars from Odessa I.I. Mechnikov national university and Perm state university. Philosophers, historians and culturologists from Russia, Ukraine, Germany, Israel, France, Italy, Moldova and Uzbekistan took part in the debates on history of eschatological conceptions in European tradition , on the morphology of historical time.
The article examines the main trends in the study of the Stalinist period and the phenomenon of Stalinism in connection with the mass opening of the archives.