Distinct changes of genomic biases in nucleotide substitution at the time of mammalian radiation

Differences in the regional substitution patterns in the human genome created patterns of large-scale variation of base composition known as genomic isochores. To gain insight into the origin of the genomic isochores we develop a maximum likelihood approach to determine the history of substitution patterns in the human genome. This approach utilizes the vast amount of repetitive sequence deposited in the human genome over the past ~250 MYR. Using this approach we estimate the frequencies of seven types of substitutions: the four transversions, two transitions, and the methyl-assisted transition of cytosine in CpG. Comparing substitutional patterns in repetitive elements of various ages, we reconstruct the history of the base-substitutional process in the different isochores for the past 250 Myr. At around 90 Myr ago (around the time of the mammalian radiation), we find an abrupt 4- to 8-fold increase of the cytosine transition rate in CpG pairs compared to that of the reptilian ancestor. Further analysis of nucleotide substitutions in regions with different GC-content reveals concurrent changes in the substitutional patterns. While the substitutional pattern was dependent on the regional GC-content in such ways that it preserved the regional GC-content before the mammalian radiation, it lost this dependence afterwards. The substitutional pattern changed from an isochore-preserving to an isochore-degrading one. We conclude that isochores have been established before the radiation of the eutherian mammals and have been subject to the process of homogenization since then

Mapping and Merging of Anatomical Ontologies

This article presents the principal results of the Ph.D. thesis Intelligent systems in bioinformatics: mapping and merging anatomical ontologies by Peter Petrov, successfully defended at the St. Kliment Ohridski University of Sofia, Faculty of Mathematics and Informatics, Department of Information Technologies, on 26 April 2013.The problem of mapping and merging ontologies in general is an important one in the area of ontology engineering. The same problem considered within the narrower area of anatomical ontologies (AOs) is important in bioinformatics because solving it could enable the transfer of data and the application of knowledge obtained from various model organisms to other model and non-model organisms, and even to research areas such as those of human health and medicine. This paper presents a detailed summary of the author’s PhD research done in the period 2007–2013. The paper’s main topic is the problem of mapping and merging of multiple species-specific AOs and the related approaches, methods, and procedures that can be used for solving it. ACM Computing Classification System (1998): J.3, E.1, G.2.2, G.2.3, I.2.1, I.2.4

Substantial regional variation in substitution rates in the human genome: importance of GC content, gene density and telomere-specific effects

This study presents the first global, 1 Mbp level analysis of patterns of nucleotide substitutions along the human lineage. The study is based on the analysis of a large amount of repetitive elements deposited into the human genome since the mammalian radiation, yielding a number of results that would have been difficult to obtain using the more conventional comparative method of analysis. This analysis revealed substantial and consistent variability of rates of substitution, with the variability ranging up to 2-fold among different regions. The rates of substitutions of C or G nucleotides with A or T nucleotides vary much more sharply than the reverse rates suggesting that much of that variation is due to differences in mutation rates rather than in the probabilities of fixation of C/G vs. A/T nucleotides across the genome. For all types of substitution we observe substantially more hotspots than coldspots, with hotspots showing substantial clustering over tens of Mbp's. Our analysis revealed that GC-content of surrounding sequences is the best predictor of the rates of substitution. The pattern of substitution appears very different near telomeres compared to the rest of the genome and cannot be explained by the genome-wide correlations of the substitution rates with GC content or exon density. The telomere pattern of substitution is consistent with natural selection or biased gene conversion acting to increase the GC-content of the sequences that are within 10-15 Mbp away from the telomere.Comment: 35 pages, 6 figure

Dimensional crossover for the beyond-mean-field correction in Bose gases

We present a detailed beyond-mean-field analysis of a weakly interacting Bose gas in the crossover from three to low dimensions. We find an analytical solution for the energy and provide a clear qualitative picture of the crossover in the case of a box potential with periodic boundary conditions. We show that the leading contribution of the confinement-induced resonance is of beyond-mean-field order and calculate the leading corrections in the three- and low-dimensional limits. We also characterize the crossover for harmonic potentials in a model system with particularly chosen short- and long-range interactions and show the limitations of the local-density approximation. Our analysis is applicable to Bose-Bose mixtures and gives a starting point for developing the beyond-mean-field theory in inhomogeneous systems with long-range interactions such as dipolar particles or Rydberg-dressed atoms.Comment: 5 pages and supplemental material, revised treatment of the harmonic confinemen