Nucleotide Frequencies in Human Genome and Fibonacci Numbers

This work presents a mathematical model that establishes an interesting connection between nucleotide frequencies in human single-stranded DNA and the famous Fibonacci's numbers. The model relies on two assumptions. First, Chargaff's second parity rule should be valid, and, second, the nucleotide frequencies should approach limit values when the number of bases is sufficiently large. Under these two hypotheses, it is possible to predict the human nucleotide frequencies with accuracy. It is noteworthy, that the predicted values are solutions of an optimization problem, which is commonplace in many nature's phenomena.Comment: 12 pages, 2 figure

A Gibbs approach to Chargaff's second parity rule

Chargaff's second parity rule (CSPR) asserts that the frequencies of short polynucleotide chains are the same as those of the complementary reversed chains. Up to now, this hypothesis has only been observed empirically and there is currently no explanation for its presence in DNA strands. Here we argue that CSPR is a probabilistic consequence of the reverse complementarity between paired strands, because the Gibbs distribution associated with the chemical energy between the bonds satisfies CSPR. We develop a statistical test to study the validity of CSPR under the Gibbsian assumption and we apply it to a large set of bacterial genomes taken from the GenBank repository.Comment: 16 page

NOBAI: a web server for character coding of geometrical and statistical features in RNA structure

The Numeration of Objects in Biology: Alignment Inferences (NOBAI) web server provides a web interface to the applications in the NOBAI software package. This software codes topological and thermodynamic information related to the secondary structure of RNA molecules as multi-state phylogenetic characters, builds character matrices directly in NEXUS format and provides sequence randomization options. The web server is an effective tool that facilitates the search for evolutionary history embedded in the structure of functional RNA molecules. The NOBAI web server is accessible at ‘http://www.manet.uiuc.edu/nobai/nobai.php’. This web site is free and open to all users and there is no login requirement

Emergence of qualia from brain activity or from an interaction of proto-consciousness with the brain: which one is the weirder? Available evidence and a research agenda

This contribution to the science of consciousness aims at comparing how two different theories can explain the emergence of different qualia experiences, meta-awareness, meta-cognition, the placebo effect, out-of-body experiences, cognitive therapy and meditation-induced brain changes, etc. The first theory postulates that qualia experiences derive from specific neural patterns, the second one, that qualia experiences derive from the interaction of a proto-consciousness with the brain\u2019s neural activity. From this comparison it will be possible to judge which one seems to better explain the different qualia experiences and to offer a more promising research agenda

Dinucleotide controlled null models for comparative RNA gene prediction

<p>Abstract</p> <p>Background</p> <p>Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak <it>et al</it>. [BMC Bioinformatics. 8:33] that RNA gene prediction programs can be biased by the genomic dinucleotide content, in particular those programs using a thermodynamic folding model including stacking energies. As a consequence, there is need for dinucleotide-preserving control strategies to assess the significance of such predictions. While there have been randomization algorithms for single sequences for many years, the problem has remained challenging for multiple alignments and there is currently no algorithm available.</p> <p>Results</p> <p>We present a program called SISSIz that simulates multiple alignments of a given average dinucleotide content. Meeting additional requirements of an accurate null model, the randomized alignments are on average of the same sequence diversity and preserve local conservation and gap patterns. We make use of a phylogenetic substitution model that includes overlapping dependencies and site-specific rates. Using fast heuristics and a distance based approach, a tree is estimated under this model which is used to guide the simulations. The new algorithm is tested on vertebrate genomic alignments and the effect on RNA structure predictions is studied. In addition, we directly combined the new null model with the RNAalifold consensus folding algorithm giving a new variant of a thermodynamic structure based RNA gene finding program that is not biased by the dinucleotide content.</p> <p>Conclusion</p> <p>SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require randomization of multiple alignments can be considered.</p> <p>Availability</p> <p>SISSIz is available as open source C code that can be compiled for every major platform and downloaded here: <url>http://sourceforge.net/projects/sissiz</url>.</p

DNA word analysis based on the distribution of the distances between symmetric words

We address the problem of discovering pairs of symmetric genomic words (i.e., words and the corresponding reversed complements) occurring at distances that are overrepresented. For this purpose, we developed new procedures to identify symmetric word pairs with uncommon empirical distance distribution and with clusters of overrepresented short distances. We speculate that patterns of overrepresentation of short distances between symmetric word pairs may allow the occurrence of non-standard DNA conformations, such as hairpin/cruciform structures. We focused on the human genome, and analysed both the complete genome as well as a version with known repetitive sequences masked out. We reported several well-defined features in the distributions of distances, which can be classified into three different profiles, showing enrichment in distinct distance ranges. We analysed in greater detail certain pairs of symmetric words of length seven, found by our procedure, characterised by the surprising fact that they occur at single distances more frequently than expecte

The Proteomic Code: a molecular recognition code for proteins

<p>Abstract</p> <p>Background</p> <p>The Proteomic Code is a set of rules by which information in genetic material is transferred into the physico-chemical properties of amino acids. It determines how individual amino acids interact with each other during folding and in specific protein-protein interactions. The Proteomic Code is part of the redundant Genetic Code.</p> <p>Review</p> <p>The 25-year-old history of this concept is reviewed from the first independent suggestions by Biro and Mekler, through the works of Blalock, Root-Bernstein, Siemion, Miller and others, followed by the discovery of a Common Periodic Table of Codons and Nucleic Acids in 2003 and culminating in the recent conceptualization of partial complementary coding of interacting amino acids as well as the theory of the nucleic acid-assisted protein folding.</p> <p>Methods and conclusions</p> <p>A novel cloning method for the design and production of specific, high-affinity-reacting proteins (SHARP) is presented. This method is based on the concept of proteomic codes and is suitable for large-scale, industrial production of specifically interacting peptides.</p

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection