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Register a new userMapping the spectrum of 3D communities in human chromosome conformation capture data
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Several experiments show that the three dimensional (3D) organization of chromosomes affects genetic processes such as transcription and gene regulation. To better understand this connection, researchers developed the Hi-C method that is able to detect the pairwise physical contacts of all chromosomal loci. The Hi-C data show that chromosomes are composed of 3D compartments that range over a variety of scales. However, it is challenging to systematically detect these cross-scale structures. Most studies have therefore designed methods for specific scales to study foremost topologically associated domains (TADs) and A/B compartments. To go beyond this limitation, we tailor a network community detection method that finds communities in compact fractal globule polymer systems. Our method allows us to continuously scan through all scales with a single resolution parameter. We found: (i) polymer segments belonging to the same 3D community do not have to be in consecutive order along the polymer chain. In other words, several TADs may belong to the same 3D community. (ii) CTCF proteins---a loop-stabilizing protein that is ascribed a big role in TAD formation---are well correlated with community borders only at one level of organization. (iii) TADs and A/B compartments are traditionally treated as two weakly related 3D structures and detected with different algorithms. With our method, we detect both by simply adjusting the resolution parameter. We therefore argue that they represent two specific levels of a continuous spectrum 3D communities, rather than seeing them as different structural entities.
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Modern biological techniques such as Hi-C permit to measure probabilities that different chromosomal regions are close in space. These probabilities can be visualised as matrices called contact maps. In this paper, we introduce a multifractal analysis of chromosomal contact maps. Our analysis reveals that Hi-C maps are bifractal, i.e. complex geometrical objects characterized by two distinct fractal dimensions. To rationalize this observation, we introduce a model that describes chromosomes as a hierarchical set of nested domains and we solve it exactly. The predicted multifractal spectrum is in excellent quantitative agreement with experimental data. Moreover, we show that our theory yields to a more robust estimation of the scaling exponent of the contact probability than existing methods. By applying this method to experimental data, we detect subtle conformational changes among chromosomes during differentiation of human stem cells.
All genes on the human Y-chromosome were studied using fractal dimension and Shannon entropy. Clear outlier clusters were identified. Among these were 6 sequences that have since been withdrawn as CDSs and 1 additional sequence that is not in the current assembly. A methodology for ranking the sequences based on deviation from average values of FD and SE was developed. The group of sequences scored among the 10% largest deviations had abnormally high likelihood to be from centromeric or pseudoautosomal regions and low likelihood to be from X-chromosome transposed regions. lncRNA sequences were also enriched among the outliers. In addition, the number of expressed genes previously identified for evolutionary study tended to not have large deviations from the average. Keywords: Y-chromosome; Shannon di-nucleotide entropy; fractal dimension; centromeric genes; gene degredation; lncRNA
We analyze the statistical properties of Poincare recurrences of Homo sapiens, mammalian and other DNA sequences taken from Ensembl Genome data base with up to fifteen billions base pairs. We show that the probability of Poincare recurrences decays in an algebraic way with the Poincare exponent $beta approx 4$ even if oscillatory dependence is well pronounced. The correlations between recurrences decay with an exponent $ u approx 0.6$ that leads to an anomalous super-diffusive walk. However, for Homo sapiens sequences, with the largest available statistics, the diffusion coefficient converges to a finite value on distances larger than million base pairs. We argue that the approach based on Poncare recurrences determines new proximity features between different species and shed a new light on their evolution history.
We study the genetic behaviour of a population formed by haploid individuals which reproduce asexually. The genetic information for each individual is stored along a bit-string (or chromosome) with L bits, where 0-bits represent the wild-type allele and 1-bits correspond to harmful mutations. Each newborn inherits this chromosome from its parent with some few random mutations: on average a fixed number m of bits are flipped. Selection is implemented according to the number N of 1-bits counted along the individuals chromosome: the smaller N the higher the probability an individual has to survive a new time step. Such a population evolves, with births and deaths, and its genetic distribution becomes stabilised after many enough generations have passed. The question we pose concerns the procedure of increasing L. The aim is to get the same distribution of relative genetic loads N/L among the equilibrated population, in spite of a larger L. Should we keep the same mutation rate m/L for different values of L? The answer is yes, which intuitively seems to be plausible. However, this conclusion is not trivial, according to our simulational results: the question involves also the population size.
In spring turnip rape (Brassica rapa L. spp. oleifera) the most promising F1 hybrid system would be the Ogu-INRA CMS/Rf system. A Kosena fertility restorer gene Rfk1, homologue of the Ogura restorer gene Rfo, was successfully transferred from oilseed rape into turnip rape and that restored the fertility in female lines carrying Ogura cms. The trait was, however, unstable in subsequent generations. The physical localization of the radish chromosomal region carrying the Rfk1 gene was investigated using 8 GISH (genomic in situ hybridization) and BAC-FISH (bacterial artificial chromosome fluorescence in situ hybridization) methods. The metaphase chromosomes were hybridized using radish DNA as the genomic probe and BAC64 probe, which is linked with Rfo gene. Both probes showed a signal in the chromosome spreads of the restorer line 4021-2 Rfk of turnip rape but not in the negative control line 4021B. The GISH analyses clearly showed that the turnip rape restorer plants were either monosomic (2n=2x=20+1R) or disomic (2n=2x=20+2R) addition lines with one or two copies of a single alien chromosome region originating from radish. In the BAC-FISH analysis, double dot signals were detected in sub-terminal parts of the radish chromosome arms showing that the fertility restorer gene Rfk1 was located in this additional radish chromosome. Detected disomic addition lines were found to be unstable for turnip rape hybrid production. Using the BAC-FISH analysis, weak signals were sometimes visible in two chromosomes of turnip rape and a homologous region of Rfk1 in chromosome 9 of the B. rapa A genome was verified with BLAST analysis. In the future this homologous area in A genome could be substituted with radish chromosome area carrying the Rfk1 gene.
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