Impact of template backbone heterogeneity on RNA polymerase II transcription.

Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA

A biological sequence comparison algorithm using quantum computers

Genetic information is encoded in a linear sequence of nucleotides, represented by letters ranging from thousands to billions. Mutations refer to changes in the DNA or RNA nucleotide sequence. Thus, mutation detection is vital in all areas of biology and medicine. Careful monitoring of virulence-enhancing mutations is essential. However, an enormous amount of classical computing power is required to analyze genetic sequences of this size. Inspired by human perception of vision and pixel representation of images on quantum computers, we leverage these techniques to implement a pairwise sequence analysis. The methodology has a potential advantage over classical approaches and can be further applied to identify mutations and other modifications in genetic sequences. We present a method to display and analyze the similarity between two genome sequences on a quantum computer where a similarity score is calculated to determine the similarity between nucleotides.Comment: 14 pages, 8 figures, 3 tables New version: typo in figure 7 New version because of a missing information in affiliations in footer, page

Chemoinformatics Research at the University of Sheffield: A History and Citation Analysis

This paper reviews the work of the Chemoinformatics Research Group in the Department of Information Studies at the University of Sheffield, focusing particularly on the work carried out in the period 1985-2002. Four major research areas are discussed, these involving the development of methods for: substructure searching in databases of three-dimensional structures, including both rigid and flexible molecules; the representation and searching of the Markush structures that occur in chemical patents; similarity searching in databases of both two-dimensional and three-dimensional structures; and compound selection and the design of combinatorial libraries. An analysis of citations to 321 publications from the Group shows that it attracted a total of 3725 residual citations during the period 1980-2002. These citations appeared in 411 different journals, and involved 910 different citing organizations from 54 different countries, thus demonstrating the widespread impact of the Group's work