Balanced Vertices in Trees and a Simpler Algorithm to Compute the Genomic Distance

This paper provides a short and transparent solution for the covering cost of white-grey trees which play a crucial role in the algorithm of Bergeron {\it et al.}\ to compute the rearrangement distance between two multichromosomal genomes in linear time ({\it Theor. Comput. Sci.}, 410:5300-5316, 2009). In the process it introduces a new {\em center} notion for trees, which seems to be interesting on its own.Comment: 6 pages, submitte

Recurring genomic breaks in independent lineages support genomic fragility

BACKGROUND: Recent findings indicate that evolutionary breaks in the genome are not randomly distributed, and that certain regions, so-called fragile regions, are predisposed to breakages. Previous approaches to the study of genomic fragility have examined the distribution of breaks, as well as the coincidence of breaks with segmental duplications and repeats, within a single species. In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages. RESULTS: We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages. Our investigation, based on Human, Chimp, Mouse, Rat, Dog and Chicken, suggests that the propensity of a chromosomal region to break is significantly correlated among independent lineages, even when covariates are considered. Furthermore, the fragile regions are enriched for segmental duplications. CONCLUSION: Based on a novel methodology, our work provides additional support for the existence of fragile regions

Increasing Alternative Promoter Repertories Is Positively Associated with Differential Expression and Disease Susceptibility

Background: Alternative Promoter (AP) usages have been shown to enable diversified transcriptional regulation of individual gene in a context-specific (e.g., pathway, cell lineage, tissue type, and development stage et. ac.) way. Aberrant uses of APs have been directly linked to mechanism of certain human diseases. However, whether or not there exists a general link between a gene’s AP repertoire and its expression diversity is currently unknown. The general relation between a gene’s AP repertoire and its disease susceptibility also remains largely unexplored. Methodology/Principal Findings: Based on the differential expression ratio inferred from all human microarray data in NCBI GEO and the list of disease genes curated in public repositories, we systemically analyzed the general relation of AP repertoire with expression diversity and disease susceptibility. We found that genes with APs are more likely to be differentially expressed and/or disease associated than those with Single Promoter (SP), and genes with more APs are more likely differentially expressed and disease susceptible than those with less APs. Further analysis showed that genes with increased number of APs tend to have increased length in all aspects of gene structure including 39 UTR, be associated with increased duplicability, and have increased connectivity in protein-protein interaction network. Conclusions: Our genome-wide analysis provided evidences that increasing alternative promoter repertories is positivel

Polynomial-time sortable stacks of burnt pancakes

Pancake flipping, a famous open problem in computer science, can be formalised as the problem of sorting a permutation of positive integers using as few prefix reversals as possible. In that context, a prefix reversal of length k reverses the order of the first k elements of the permutation. The burnt variant of pancake flipping involves permutations of signed integers, and reversals in that case not only reverse the order of elements but also invert their signs. Although three decades have now passed since the first works on these problems, neither their computational complexity nor the maximal number of prefix reversals needed to sort a permutation is yet known. In this work, we prove a new lower bound for sorting burnt pancakes, and show that an important class of permutations, known as "simple permutations", can be optimally sorted in polynomial time.Comment: Accepted pending minor revisio

Generalizations of Markov model to characterize biological sequences

BACKGROUND: The currently used k(th )order Markov models estimate the probability of generating a single nucleotide conditional upon the immediately preceding (gap = 0) k units. However, this neither takes into account the joint dependency of multiple neighboring nucleotides, nor does it consider the long range dependency with gap>0. RESULT: We describe a configurable tool to explore generalizations of the standard Markov model. We evaluated whether the sequence classification accuracy can be improved by using an alternative set of model parameters. The evaluation was done on four classes of biological sequences – CpG-poor promoters, all promoters, exons and nucleosome positioning sequences. Using di- and tri-nucleotide as the model unit significantly improved the sequence classification accuracy relative to the standard single nucleotide model. In the case of nucleosome positioning sequences, optimal accuracy was achieved at a gap length of 4. Furthermore in the plot of classification accuracy versus the gap, a periodicity of 10–11 bps was observed which might indicate structural preferences in the nucleosome positioning sequence. The tool is implemented in Java and is available for download at . CONCLUSION: Markov modeling is an important component of many sequence analysis tools. We have extended the standard Markov model to incorporate joint and long range dependencies between the sequence elements. The proposed generalizations of the Markov model are likely to improve the overall accuracy of sequence analysis tools

A Tutorial of the Poisson Random Field Model in Population Genetics

Population genetics is the study of allele frequency changes driven by various evolutionary forces such as mutation, natural selection, and random genetic drift. Although natural selection is widely recognized as a bona-fide phenomenon, the extent to which it drives evolution continues to remain unclear and controversial. Various qualitative techniques, or so-called “tests of neutrality”, have been introduced to detect signatures of natural selection. A decade and a half ago, Stanley Sawyer and Daniel Hartl provided a mathematical framework, referred to as the Poisson random field (PRF), with which to determine quantitatively the intensity of selection on a particular gene or genomic region. The recent availability of large-scale genetic polymorphism data has sparked widespread interest in genome-wide investigations of natural selection. To that end, the original PRF model is of particular interest for geneticists and evolutionary genomicists. In this article, we will provide a tutorial of the mathematical derivation of the original Sawyer and Hartl PRF model

Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons

An integrative strategy of comparative genomics, experimental and computational approaches reveals aspects of a regulatory network controlling neuronal-specific expression in presynaptic neurons

CYNTENATOR: Progressive Gene Order Alignment of 17 Vertebrate Genomes

Whole genome gene order evolution in higher eukaryotes was initially considered as a random process. Gene order conservation or conserved synteny was seen as a feature of common descent and did not imply the existence of functional constraints. This view had to be revised in the light of results from sequencing dozens of vertebrate genomes

Position and distance specificity are important determinants of cis-regulatory motifs in addition to evolutionary conservation

Computational discovery of cis-regulatory elements remains challenging. To cope with the high false positives, evolutionary conservation is routinely used. However, conservation is only one of the attributes of cis-regulatory elements and is neither necessary nor sufficient. Here, we assess two additional attributes—positional and inter-motif distance specificity—that are critical for interactions between transcription factors. We first show that for a greater than expected fraction of known motifs, the genes that contain the motifs in their promoters in a position-specific or distance-specific manner are related, both in function and/or in expression pattern. We then use the position and distance specificity to discover novel motifs. Our work highlights the importance of distance and position specificity, in addition to the evolutionary conservation, in discovering cis-regulatory motifs

The Fibers and Range of Reduction Graphs in Ciliates

The biological process of gene assembly has been modeled based on three types of string rewriting rules, called string pointer rules, defined on so-called legal strings. It has been shown that reduction graphs, graphs that are based on the notion of breakpoint graph in the theory of sorting by reversal, for legal strings provide valuable insights into the gene assembly process. We characterize which legal strings obtain the same reduction graph (up to isomorphism), and moreover we characterize which graphs are (isomorphic to) reduction graphs.Comment: 24 pages, 13 figure