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At least 19 recordsLinked to original sources

arXiv2011

Chargaff's "Grammar of Biology": New Fractal-like Rules

Chargaff once said that "I saw before me in dark contours the beginning of a grammar of Biology". In linguistics, "grammar" is the set of natural language rules, but we do not know for sure what Chargaff meant by "grammar" of Biology. Nevertheless, assuming the metaphor, Chargaff himself started a "grammar of Biology" discovering the so called Chargaff's rules. In this work, we further develop his grammar. Using new concepts, we were able to discovery new genomic rules that seem to be invariant across a large set of organisms, and show a fractal-like property, since no matter the scale, the same pattern is observed (self-similarity). We hope that these new invariant genomic rules may be used in different contexts since short read data bias detection to genome assembly quality assessment.

q-bio.GN↗

arXiv2023

Bugs as Features (Part I): Concepts and Foundations for the Compositional Data Analysis of the Microbiome-Gut-Brain Axis

There has been a growing acknowledgement of the involvement of the gut microbiome - the collection of microbes that reside in our gut - in regulating our mood and behaviour. This phenomenon is referred to as the microbiome-gut-brain axis. While our techniques to measure the presence and abundance of these microbes have been steadily improving, the analysis of microbiome data is non-trivial. Here, we present a perspective on the concepts and foundations of data analysis and interpretation of microbiome experiments with a focus on the microbiome-gut-brain axis domain. We give an overview of foundational considerations prior to commencing analysis alongside the core microbiome analysis approaches of alpha diversity, beta diversity, differential feature abundance and functional inference. We emphasize the compositional data analysis (CoDA) paradigm. Further, this perspective features an extensive and heavily annotated microbiome analysis in R in the supplementary materials, as a resource for new and experienced bioinformaticians alike.

q-bio.GN↗

arXiv2007

Holographic bound and protein linguistics

The holographic bound in physics constrains the complexity of life. The finite storage capability of information in the observable universe requires the protein linguistics in the evolution of life. We find that the evolution of genetic code determines the variance of amino acid frequencies and genomic GC content among species. The elegant linguistic mechanism is confirmed by the experimental observations based on all known entire proteomes.

q-bio.GN↗

arXiv2007

Mismatch Repair Error Implies Chargaff's Second Parity Rule

Chargaff's second parity rule holds empirically for most types of DNA that along single strands of DNA the base contents are equal for complimentary bases, A = T, G = C. A Markov chain model is constructed to track the evolution of any single base position along single strands of genomes whose organisms are equipped with replication mismatch repair. Under the key assumptions that mismatch error rates primarily depend the number of hydrogen bonds of nucleotides and that the mismatch repairing process itself makes strand recognition error, the model shows that the steady state probabilities for any base position to take on one of the 4 nucleotide bases are equal for complimentary bases. As a result, Chargaff's second parity rule is the manifestation of the Law of Large Number acting on the steady state probabilities. More importantly, because the model pinpoints mismatch repair as a basis of the rule, it is suitable for experimental verification.

q-bio.GN↗

arXiv2007

Multiple pattern matching: A Markov chain approach

RNA motifs typically consist of short, modular patterns that include base pairs formed within and between modules. Estimating the abundance of these patterns is of fundamental importance for assessing the statistical significance of matches in genomewide searches, and for predicting whether a given function has evolved many times in different species or arose from a single common ancestor. In this manuscript, we review in an integrated and self-contained manner some basic concepts of automata theory, generating functions and transfer matrix methods that are relevant to pattern analysis in biological sequences. We formalize, in a general framework, the concept of Markov chain embedding to analyze patterns in random strings produced by a memoryless source. This conceptualization, together with the capability of automata to recognize complicated patterns, allows a systematic analysis of problems related to the occurrence and frequency of patterns in random strings. The applications we present focus on the concept of synchronization of automata, as well as automata used to search for a finite number of keywords (including sets of patterns generated according to base pairing rules) in a general text.

math.PR↗

arXiv2007

Non-coding DNA programs express adaptation and its universal law

Significant fraction (98.5% in humans) of most animal genomes is non- coding dark matter. Its largely unknown function (1-5) is related to programming (rather than to spontaneous mutations) of accurate adaptation to rapidly changing environment. Programmed adaptation to the same universal law for non-competing animals from anaerobic yeast to human is revealed in the study of their extensively quantified mortality (6-21). Adaptation of animals with removed non-coding DNA fractions may specify their contribution to genomic programming. Emergence of new adaptation programs and their (non-Mendelian) heredity may be studied in antibiotic mini-extinctions (22-24). On a large evolutionary scale rapid universal adaptation was vital for survival, and evolved, in otherwise lethal for diverse species major mass extinctions (25-28). Evolutionary and experimental data corroborate these conclusions (6-21, 29-32). Universal law implies certain biological universality of diverse species, thus quantifies applicability of animal models to humans). Genomic adaptation programming calls for unusual approach to its study and implies unanticipated perspectives, in particular, directed biological changes.

q-bio.GN↗

arXiv2007

Chromatin Folding in Relation to Human Genome Function

Three-dimensional (3D) chromatin structure is closely related to genome function, in particular transcription. However, the folding path of the chromatin fiber in the interphase nucleus is unknown. Here, we systematically measured the 3D physical distance between pairwise labeled genomic positions in gene-dense, highly transcribed domains and gene-poor less active areas on chromosomes 1 and 11 in G1 nuclei of human primary fibroblasts, using fluorescence in situ hybridization. Interpretation of our results and those published by others, based on polymer physics, shows that the folding of the chromatin fiber can be described as a polymer in a globular state (GS), maintained by intra-polymer attractive interactions that counteract self-avoidance forces. The GS polymer model is able to describe chromatin folding in as well the highly expressed domains as the lowly expressed ones, indicating that they differ in Kuhn length and chromatin compaction. Each type of genomic domain constitutes an ensemble of relatively compact globular folding states, resulting in a considerable cellto- cell variation between otherwise identical cells. We present evidence for different polymer folding regimes of the chromatin fiber on the length scale of a few mega base pairs and on that of complete chromosome arms (several tens of Mb). Our results present a novel view on the folding of the chromatin fiber in interphase and open the possibility to explore the nature of the intra-chromatin fiber interactions.

q-bio.GN↗

arXiv2007

In silico evidence of the relationship between miRNAs and siRNAs

Both short interfering RNAs (siRNAs) and microRNAs (miRNAs) mediate the repression of specific sequences of mRNA through the RNA interference pathway. In the last years several experiments have supported the hypothesis that siRNAs and miRNAs may be functionally interchangeable, at least in cultured cells. In this work we verify that this hypothesis is also supported by a computational evidence. We show that a method specifically trained to predict the activity of the exogenous siRNAs assigns a high silencing level to experimentally determined human miRNAs. This result not only supports the idea of siRNAs and miRNAs equivalence but indicates that it is possible to use computational tools developed using synthetic small interference RNAs to investigate endogenous miRNAs.

q-bio.BM↗

arXiv2009

The influence of horizontal gene transfer on the mean fitness of unicellular populations in static environments

This paper develops a mathematical model describing the influence that conjugation-mediated Horizontal Gene Transfer (HGT) has on the mutation-selection balance in an asexually reproducing population of unicellular, prokaryotic organisms. It is assumed that mutation-selection balance is reached in the presence of a fixed background concentration of antibiotic, to which the population must become resistant in order to survive. We analyze the behavior of the model in the limit of low and high antibiotic-induced first-order death rate constants, and find that the highest mean fitness is obtained at low rates of bacterial conjugation. As the rate of conjugation crosses a threshold, the mean fitness decreases to a minimum, and then rises asymptotically to a limiting value as the rate of conjugation becomes infinitely large. However, this limiting value is smaller than the mean fitness obtained in the limit of low conjugation rate. This dependence of the mean fitness on the conjugation rate is fairly small for the parameter ranges we have considered, and disappears as the first-order death rate constant due to the presence of antibiotic approaches zero. For large values of the antibiotic death rate constant, we have obtained an analytical solution for the behavior of the mean fitness that agrees well with the results of simulations. The results of this paper suggest that conjugation-mediated HGT has a slightly deleterious effect on the mean fitness of a population at mutation-selection balance. Therefore, we argue that HGT confers a selective advantage by allowing for faster adaptation to a new or changing environment. The results of this paper are consistent with the observation that HGT can be promoted by environmental stresses on a population.

q-bio.PE↗

arXiv2007

Reciprocal best hits are not a logically sufficient condition for orthology

It is common to use reciprocal best hits, also known as a boomerang criterion, for determining orthology between sequences. The best hits may be found by blast, or by other more recently developed algorithms. Previous work seems to have assumed that reciprocal best hits is a sufficient but not necessary condition for orthology. In this article, I explain why reciprocal best hits cannot logically be a sufficient condition for orthology. If reciprocal best hits is neither sufficient nor necessary for orthology, it would seem worthwhile to examine further the logical foundations of some unsupervised algorithms that are used to identify orthologs.

q-bio.GN↗

arXiv2007

Codon Usage Bias Measured Through Entropy Approach

Codon usage bias measure is defined through the mutual entropy calculation of real codon frequency distribution against the quasi-equilibrium one. This latter is defined in three manners: (1) the frequency of synonymous codons is supposed to be equal (i.e., the arithmetic mean of their frequencies); (2) it coincides to the frequency distribution of triplets; and, finally, (3) the quasi-equilibrium frequency distribution is defined as the expected frequency of codons derived from the dinucleotide frequency distribution. The measure of bias in codon usage is calculated for 125 bacterial genomes.

q-bio.GN↗

arXiv2007

RNA polymerase motors on DNA track: effects of traffic congestion on RNA synthesis

RNA polymerase (RNAP) is an enzyme that synthesizes a messenger RNA (mRNA) strand which is complementary to a single-stranded DNA template. From the perspective of physicists, an RNAP is a molecular motor that utilizes chemical energy input to move along the track formed by a ssDNA. In some circumstances, which are described in this paper, a large number of RNAPs move simultaneously along the same track. We refer to such collective movements of the RNAPs as RNAP traffic because of the similarities between the collective dynamics of the RNAPs on ssDNA track and that of vehicles in highway traffic. In this paper we develop a theoretical model for RNAP traffic by incorporating the steric interactions between RNAPs as well as the mechano-chemical cycle of individual RNAPs during the elongation of the mRNA. By a combination of analytical and numerical techniques, we calculate the rates of mRNA synthesis and the average density profile of the RNAPs on the ssDNA track. We also suggest novel experiments for testing our theoretical predictions.

physics.bio-ph↗

arXiv2007

OrfMapper: A Web-Based Application for Visualizing Gene Clusters on Metabolic Pathway Maps

Computational analyses of, e.g., genomic, proteomic, or metabolomic data, commonly result in one or more sets of candidate genes, proteins, or enzymes. These sets are often the outcome of clustering algorithms. Subsequently, it has to be tested if, e.g., the candidate gene-products are members of known metabolic processes. With OrfMapper we provide a powerful but easy-to-use, web-based database application, that supports such analyses. All services provided by OrfMapper are freely available at http://www.orfmapper.com

q-bio.GN↗

arXiv2008

Introducing a Probabilistic Structure on Sequential Dynamical Systems, Simulation and Reduction of Probabilistic Sequential Networks

A probabilistic structure on sequential dynamical systems is introduced here, the new model will be called Probabilistic Sequential Network, PSN. The morphisms of Probabilistic Sequential Networks are defined using two algebraic conditions. It is proved here that two homomorphic Probabilistic Sequential Networks have the same equilibrium or steady state probabilities if the morphism is either an epimorphism or a monomorphism. Additionally, the proof of the set of PSN with its morphisms form the category PSN, having the category of sequential dynamical systems SDS, as a full subcategory is given. Several examples of morphisms, subsystems and simulations are given.

q-bio.GN↗

arXiv2007

Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions

3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.

q-bio.GN↗

arXiv2007

p-Adic Degeneracy of the Genetic Code

Degeneracy of the genetic code is a biological way to minimize effects of the undesirable mutation changes. Degeneration has a natural description on the 5-adic space of 64 codons $\mathcal{C}_5 (64) = \{n_0 + n_1 5 + n_2 5^2 : n_i = 1, 2, 3, 4 \} ,$ where $n_i$ are digits related to nucleotides as follows: C = 1, A = 2, T = U = 3, G = 4. The smallest 5-adic distance between codons joins them into 16 quadruplets, which under 2-adic distance decay into 32 doublets. p-Adically close codons are assigned to one of 20 amino acids, which are building blocks of proteins, or code termination of protein synthesis. We shown that genetic code multiplets are made of the p-adic nearest codons.

q-bio.GN↗

arXiv2007

Monte Carlo Simulation and Statistical Analysis of the Effect of Coding Table Specificity on Genetic Information Coding

We present a computer simulation, which is inspired by Penna model, to help understanding the effect of genetic coding tables on population dynamics. To represent populations we used real and artificial gene sequences in this model. We coded these sequences using different amino acid tables in Nature, the standard table as well as the tables which are used by mithocondria and some eukaryotes. Contrary to common belief we find that the standard code table which is used in most organisms in Nature, does not give the most resilient coding against point mutations.

q-bio.PE↗

arXiv2007

On Cycles in the Transcription Network of Saccharomyces cerevisiae

We investigate the cycles in the transcription network of S. cerevisiae. Unlike a similar network of E. coli, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell. Almost all cycles in the transcription network of S. cerevisiae are contained in a single strongly connected component, which we call LSCC (L for ``largest''), except for a single cycle of two transcription factors. Among different physiological conditions, cell cycle has the most significant relationship with LSCC, as the set of 64 transcription interactions that are active in all phases of the cell cycle has overlap of 27 with the interactions of LSCC (of which there are 49). Conversely, if we remove the interactions that are active in all phases of the cell cycle (fewer than 1% of the total), the LSCC would have only three nodes and 5 edges, 4 of which are active only in the stress response subnetwork. LSCC has a special place in the topology of the network and it can be used to define a natural hierarchy in the network; in every physiological subnetwork LSCC plays a pivotal role. Apart from those well-defined conditions, the transcription network of S. cerevisiae is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are exogenous: diauxic shift and DNA repair, while cell cycle, sporulation are endogenous.

q-bio.MN↗