Range-limited Heaps' law for functional DNA words in the human genome.

Heaps' or Herdan-Heaps' law is a linguistic law describing the relationship between the vocabulary/dictionary size (type) and word counts (token) to be a power-law function. Its existence in genomes with certain definition of DNA words is unclear partly because the dictionary size in genome could be much smaller than that in a human language. We define a DNA word as a coding region in a genome that codes for a protein domain.

Noether's Theorem as a Metaphor for Chargaff's 2nd Parity Rule in Genomics.

In the present note, the genomic compositional rule largely known as 'Chargaff's 2nd parity rule' (asserting equimolarity between Adenine-Thymine and Guanine-Cytosine in any of the two DNA strands) is regarded in association with Noether's theorem linking symmetries with conservation laws in physics. In the case of the genome, the strict physical and mathematical prerequisites of Noether's theorem do not hold. However, we conclude that a metaphor can be established with Noether's theorem, as inter-strand symmetry concerning DNA functionality engenders specific features in genome composition.

Introduction of 'Generalized Genomic Signatures' for the quantification of neighbour preferences leads to taxonomy- and functionality-based distinction among sequences.

Analysis of DNA composition at several length scales constitutes the bulk of many early studies aimed at unravelling the complexity of the organization and functionality of genomes. Dinucleotide relative abundances are considered an idiosyncratic feature of genomes, regarded as a 'genomic signature'. Motivated by this finding, we introduce the 'Generalized Genomic Signatures' (GGSs), composed of over- and under-abundances of all oligonucleotides of a given length, thus filtering out compositional trends and neighbour preferences at any shorter range.

Ultra-High Dilutions and Homeopathy: Can They Be Explained without Non-Local Theory?

We discuss questions related to the 'Benveniste Affair', its consequences and broader issues in an attempt to understand homeopathy. Specifically, we address the following points: 1.:  The relationship between the experiments conducted by Benveniste, Montagnier, their collaborators and groups that independently tested their results, and 'traditional' homeopathy.

On avoided words, absent words, and their application to biological sequence analysis.

Background: The deviation of the observed frequency of a word from its expected frequency in a given sequence is used to determine whether or not the word is . This concept is particularly useful in DNA linguistic analysis. The value of the deviation of , denoted by [Formula: see text], effectively characterises the extent of a word by its edge contrast in the context in which it occurs.

A novel skew analysis reveals substitution asymmetries linked to genetic code GC-biases and PolIII a-subunit isoforms.

Strand biases reflect deviations from a null expectation of DNA evolution that assumes strand-symmetric substitution rates. Here, we present strong evidence that nearest-neighbour preferences are a strand-biased feature of bacterial genomes, indicating neighbour-dependent substitution asymmetries. To detect such asymmetries we introduce an alignment free index (relative abundance skews).

Fractality and entropic scaling in the chromosomal distribution of conserved noncoding elements in the human genome.

Conserved non-coding elements (CNEs) are defined using various degrees of sequence identity and thresholds of minimal length. Their conservation frequently exceeds the one observed for protein-coding sequences. We explored the chromosomal distribution of different classes of CNEs in the human genome.

An overview of the BIOASQ large-scale biomedical semantic indexing and question answering competition.

Background: This article provides an overview of the first BIOASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013. BIOASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.

Results: The 2013 BIOASQ competition comprised two tasks, Task 1a and Task 1b.

Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution.

CpG Islands (CGIs) are compositionally defined short genomic stretches, which have been studied in the human, mouse, chicken and later in several other genomes. Initially, they were assigned the role of transcriptional regulation of protein-coding genes, especially the house-keeping ones, while more recently there is found evidence that they are involved in several other functions as well, which might include regulation of the expression of RNA genes, DNA replication etc. Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or "orphan" CGIs).

Classification of selectively constrained DNA elements using feature vectors and rule-based classifiers.

Scarce work has been done in the analysis of the composition of conserved non-coding elements (CNEs) that are identified by comparisons of two or more genomes and are found to exist in all metazoan genomes. Here we present the analysis of CNEs with a methodology that takes into account word occurrence at various lengths scales in the form of feature vector representation and rule based classifiers. We implement our approach on both protein-coding exons and CNEs, originating from human, insect (Drosophila melanogaster) and worm (Caenorhabditis elegans) genomes, that are either identified in the present study or obtained from the literature.

Conserved noncoding elements follow power-law-like distributions in several genomes as a result of genome dynamics.

Conserved, ultraconserved and other classes of constrained elements (collectively referred as CNEs here), identified by comparative genomics in a wide variety of genomes, are non-randomly distributed across chromosomes. These elements are defined using various degrees of conservation between organisms and several thresholds of minimal length. We here investigate the chromosomal distribution of CNEs by studying the statistical properties of distances between consecutive CNEs.

Evolutionary constraints favor a biophysical model explaining hox gene collinearity.

The Hox gene collinearity enigma has often been approached using models based on biomolecular mechanisms. The biophysical model is an alternative approach based on the hypothesis that collinearity is caused by physical forces pulling the Hox genes from a territory where they are inactive to a distinct spatial domain where they are activated in a step by step manner. Such Hox gene translocations have recently been observed in support of the biophysical model.

Homeopathy--between tradition and modern science: remedies as carriers of significance.

The healing potential and description of homeopathic remedies, as determined in homeopathic pathogenic trials (HPTs) and verified by medical experience, are often found to be meaningfully connected with the symbolic content attributed to the original materials (tinctures, metals etc) through tradition or modern semantics. Such a connection is incompatible with a biomolecular mechanistic explanation of the healing action of remedies. The physiological effects of crude substances are often similar to the symptoms of illnesses cured by the corresponding homeopathic remedy.

Widespread occurrence of power-law distributions in inter-repeat distances shaped by genome dynamics.

Repetitive DNA sequences derived from transposable elements (TE) are distributed in a non-random way, co-clustering with other classes of repeat elements, genes and other genomic components. In a previous work we reported power-law-like size distributions (linearity in log-log scale) in the spatial arrangement of Alu and LINE1 elements in the human genome. Here we investigate the large-scale features of the spatial arrangement of all principal classes of TEs in 14 genomes from phylogenetically distant organisms by studying the size distribution of inter-repeat distances.

Scaling properties and fractality in the distribution of coding segments in eukaryotic genomes revealed through a block entropy approach.

Statistical methods, including block entropy based approaches, have already been used in the study of long-range features of genomic sequences seen as symbol series, either considering the full alphabet of the four nucleotides or the binary purine or pyrimidine character set. Here we explore the alternation of short protein-coding segments with long noncoding spacers in entire chromosomes, focusing on the scaling properties of block entropy. In previous studies, it has been shown that the sizes of noncoding spacers follow power-law-like distributions in most chromosomes of eukaryotic organisms from distant taxa.

Power-laws in the genomic distribution of coding segments in several organisms: an evolutionary trace of segmental duplications, possible paleopolyploidy and gene loss.

Large-scale features of the spatial arrangement of protein-coding segments (PCS) are investigated by means of the inter-PCS spacers' size distributions, which have been found to follow power-laws. Linearity in double-logarithmic scale extends to several orders of magnitude in the genomes of organisms as disparate as mammals, insects and plants. This feature is also present in the most compact eukaryotic genomes and in half of the examined bacteria, despite their very limited non-coding space.

Alu and LINE1 distributions in the human chromosomes: evidence of global genomic organization expressed in the form of power laws.

Spatial distribution and clustering of repetitive elements are extensively studied during the last years, as well as their colocalization with other genomic components. Here we investigate the large-scale features of Alu and LINE1 spatial arrangement in the human genome by studying the size distribution of interrepeat distances. In most cases, we have found power-law size distributions extending in several orders of magnitude.

Deviations from Chargaff's second parity rule in organellar DNA Insights into the evolution of organellar genomes.

Chargaff' s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA. This is indeed the case for all bacterial and eukaryotic genomes studied, although the genomic patterns may differ among genomes in terms of local deviations. The behaviour of organellar genomes regarding the second parity rule has not been studied in detail up to now.

A study on the correlation of nucleotide skews and the positioning of the origin of replication: different modes of replication in bacterial species.

Deviations from Chargaff's 2nd parity rule, according to which A approximately T and G approximately C in single stranded DNA, have been associated with replication as well as with transcription in prokaryotes. Based on observations regarding mainly the transcription-replication co-linearity in a large number of prokaryotic species, we formulate the hypothesis that the replication procedure may follow different modes between genomes throughout which the skews clearly follow different patterns. We draw the conclusion that multiple functional sites of origin of replication may exist in the genomes of most archaea and in some exceptional cases of eubacteria, while in the majority of eubacteria, replication occurs through a single fixed origin.

"Word" preference in the genomic text and genome evolution: different modes of n-tuplet usage in coding and noncoding sequences.

Extensive work on n-tuplet occurrence in genomic sequences has revealed the correlation of their usage with sequence origin. Parallel to that, there exist different restrictions in the nucleotide composition of coding and noncoding sequences that may result in distinct modes of usage of n-tuplets. The relatively simple approaches described herein focus on such differences.

Multi-criterial coding sequence prediction. Combination of GeneMark with two novel, coding-character specific quantities.

This work applies two recently formulated quantities, strongly correlated with the coding character of a sequence, as an additional "module" on GeneMark, in a three-criterial method. The difference in the statistical approaches implicated by the methods combined here, is expected to contribute to an efficient assignment of functionality to unannotated genomic sequences. The developed combined algorithm is used to fractionalize a collection of GeneMark-predicted exons into sub-collections of different expectation to be coding.

Measuring the coding potential of genomic sequences through a combination of triplet occurrence patterns and RNY preference.

The distribution of n-tuplet frequencies is shown to strongly correlate with functionality when examining a genomic sequence in a reading-frame specific manner. The approach described herein applies a coarse-graining procedure, which is able to reveal aspects of triplet usage that are related to protein coding, while at the same time remaining species independent, based on a simple summation of suitable triplet occurrences measures. These quantities are ratios of simple frequencies to suitable mononucleotide-frequency products promoting the incidence of the RNY motif, preferred in the most widely used codons.

Mutually symmetric and complementary triplets: differences in their use distinguish systematically between coding and non-coding genomic sequences.

The general property of asymmetry in word use in meaningful texts written in a variety of languages, motivates a quantification of the differences in the use of mutually symmetric triplets in genomic sequences. When this is done in the three reading frames, high values found for one of them are used as indication that the sequence is coding for a protein. Moreover, a similar quantification of the differences in the use of complementary triplets is introduced, again with predictive power of the coding character of a sequence.