Searcharxiv⌕ Search

SEARCH · Searcharxiv

Results for “q-bio.GN”

Search indexed arXiv papers on artificial intelligence, large language models, computer vision and robotics. Read source abstracts and follow links to arXiv.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

Identification of possible differences in coding and non-coding fragments of DNA sequences by using the method of the Recurrence Quantification Analysis

Starting with the results of Li et al. in 1992 there is valuable interest in finding long range correlations in dna sequences since it raises questions about the role of introns and intron-containing genes. In the present paper we studied two sequences. We applied the method of the recurrence quantification analysis (rqa) that was introduced by Zbilut and Webber in 1994. The significant result that we have here is that both Lmax and Laminarity exhibit very large values in non coding respect to coding sequences. Therefore we suggest that there the claimed higher long range correlations of introns respect to exons from many authors may be explained here in reason of such found higher values of Lmax and of Laminarity.

q-bio.GN↗

Starr: Simple Tiling Array Analysis of Affymetrix ChIP-chip data

Chromatin immunoprecipitation combined with DNA microarrays (ChIP-chip) is an assay for DNA-protein-binding or post-translational chromatin/histone modifications. As with all high-throughput technologies, it requires a thorough bioinformatic processing of the data for which there is no standard yet. The primary goal is the reliable identification and localization of genomic regions that bind a specific protein. The second step comprises comparison of binding profiles of functionally related proteins, or of binding profiles of the same protein in different genetic backgrounds or environmental conditions. Ultimately, one would like to gain a mechanistic understanding of the effects of DNA binding events on gene expression. We present a free, open-source R package Starr that, in combination with the package Ringo, facilitates the comparative analysis of ChIP-chip data across experiments and across different microarray platforms. Core features are data import, quality assessment, normalization and visualization of the data, and the detection of ChIP-enriched genomic regions. The use of common Bioconductor classes ensures the compatibility with other R packages. Most importantly, Starr provides methods for integration of complementary genomics data, e.g., it enables systematic investigation of the relation between gene expression and dna binding.

q-bio.QM↗

Progressive Mauve: Multiple alignment of genomes with gene flux and rearrangement

Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms. We describe a method to align two or more genomes that have undergone large-scale recombination, particularly genomes that have undergone substantial amounts of gene gain and loss (gene flux). The method utilizes a novel alignment objective score, referred to as a sum-of-pairs breakpoint score. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The progressive genome alignment algorithm demonstrates markedly improved accuracy over previous approaches in situations where genomes have undergone realistic amounts of genome rearrangement, gene gain, loss, and duplication. We apply the progressive genome alignment algorithm to a set of 23 completely sequenced genomes from the genera Escherichia, Shigella, and Salmonella. The 23 enterobacteria have an estimated 2.46Mbp of genomic content conserved among all taxa and total unique content of 15.2Mbp. We document substantial population-level variability among these organisms driven by homologous recombination, gene gain, and gene loss. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve .

q-bio.GN↗

Age, Sex, and Genetic Architecture of Human Gene Expression in EBV Transformed Cell Lines

Individual expression profiles from EBV transformed cell lines are an emerging resource for genomic investigation. In this study we characterize the effects of age, sex, and genetic variation on gene expression by surveying public datasets of such profiles. We establish that the expression space of cell lines maintains genetic as well as non-germline information, in an individual-specific and cross-tissue manner. Age of donor is associated with the expression of 949 genes in the derived cell line. Age-associated genes include over-representation of immune-related genes, specifically MHC Class I genes, a phenomenon that replicates across tissues and organisms. Sex associated genes in these cell lines include likely candidates, such as genes that escape X-inactivation,testis specific expressed genes, androgen and estrogen specific genes, but also gene families previously unknown to be sex associated such as common microRNA targets (MIR-490, V_ARP1_01, MIR-489). Finally, we report 494 transcripts whose expression levels are associated with a genetic variant in cis, overlapping and validating previous reports. Incorporating age in analysis of association facilitates additional discovery of trans-acting regulatory genetic variants. Our findings promote expression profiling of transformed cell lines as a vehicle for understanding cellular systems beyond the specific lines.

q-bio.GN↗

Modelling survival and allele complementation in the evolution of genomes with polymorphic loci

We have simulated the evolution of sexually reproducing populations composed of individuals represented by diploid genomes. A series of eight bits formed an allele occupying one of 128 loci of one haploid genome (chromosome). The environment required a specific activity of each locus, this being the sum of the activities of both alleles located at the corresponding loci on two chromosomes. This activity is represented by the number of bits set to zero. In a constant environment the best fitted individuals were homozygous with alleles' activities corresponding to half of the environment requirement for a locus (in diploid genome two alleles at corresponding loci produced a proper activity). Changing the environment under a relatively low recombination rate promotes generation of more polymorphic alleles. In the heterozygous loci, alleles of different activities complement each other fulfilling the environment requirements. Nevertheless, the genetic pool of populations evolves in the direction of a very restricted number of complementing haplotypes and a fast changing environment kills the population. If simulations start with all loci heterozygous, they stay heterozygous for a long time.

q-bio.GN↗

Adaptive BLASTing through the Sequence Dataspace: Theories on Protein Sequence Embedding

We theorize that phylogenetic profiles provide a quantitative method that can relate the structural and functional properties of proteins, as well as their evolutionary relationships. A key feature of phylogenetic profiles is the interoperable data format (e.g. alignment information, physiochemical information, genomic information, etc). Indeed, we have previously demonstrated Position Specific Scoring Matrices (PSSMs) are an informative M-dimension which can be scored from quantitative measure of embedded or unmodified sequence alignments. Moreover, the information obtained from these alignments is informative, even in the twilight zone of sequence similarity (<25% identity)(1-5). Although powerful, our previous embedding strategy suffered from contaminating alignments(embedded AND unmodified) and computational expense. Herein, we describe the logic and algorithmic process for a heuristic embedding strategy (Adaptive GDDA-BLAST, Ada-BLAST). Ada-BLAST on average up to ~19-fold faster and has similar sensitivity to our previous method. Further, we provide data demonstrating the benefits of embedded alignment measurements for isolating secondary structural elements and the classifying transmembrane-domain structure/function. We theorize that sequence-embedding is one of multiple ways that low-identity alignments can be measured and incorporated into high-performance PSSM-based phylogenetic profiles.

q-bio.QM↗

Evolutionary Placement of Short Sequence Reads

We present an Evolutionary Placement Algorithm (EPA) for the rapid assignment of sequence fragments (short reads) to branches of a given phylogenetic tree under the Maximum Likelihood (ML) model. The accuracy of the algorithm is evaluated on several real-world data sets and compared to placement by pair-wise sequence comparison, using edit distances and BLAST. We test two versions of the placement algorithm, one slow and more accurate where branch length optimization is conducted for each short read insertion and a faster version where the branch lengths are approximated at the insertion position. For the slow version, additional heuristic techniques are explored that almost yield the same run time as the fast version, with only a small loss of accuracy. When those additional heuristics are employed the run time of the more accurate algorithm is comparable to that of a simple BLAST search for data sets with a high number of short query sequences. Moreover, the accuracy of the Evolutionary Placement Algorithm is significantly higher, in particular when the taxon sampling of the reference topology is sparse or inadequate. Our algorithm, which has been integrated into RAxML, therefore provides an equally fast but more accurate alternative to BLAST for phylogeny-aware analysis of short-read sequence data.

q-bio.GN↗

Physico-chemical modelling of target depletion during hybridisation on oligonulceotide microarrays

The effect of target molecule depletion from the supernatant solution is incorporated into a physico-chemical model of hybridisation on oligonucleotide microarrays. Two possible regimes are identified: local depletion, in which depletion by a given probe feature only affects that particular probe, and global depletion, in which all features responding to a given target species are affected. Examples are given of two existing spike-in data sets experiencing measurable effects of target depletion. The first of these, from an experiment by Suzuki et al. using custom built arrays with a broad range of probe lengths and mismatch positions, is verified to exhibit local and not global depletion. The second dataset, the well known Affymetrix HGU133a latin square experiment is shown to be very well explained by a global depletion model. It is shown that microarray calibrations relying on Langmuir isotherm models which ignore depletion effects will significantly underestimate specific target concentrations. It is also shown that a combined analysis of perfect match and mismatch probe signals in terms of a simple graphical summary, namely the hook curve method, can discriminate between cases of local and global depletion.

q-bio.GN↗

Computing the likelihood of sequence segmentation under Markov modelling

I tackle the problem of partitioning a sequence into homogeneous segments, where homogeneity is defined by a set of Markov models. The problem is to study the likelihood that a sequence is divided into a given number of segments. Here, the moments of this likelihood are computed through an efficient algorithm. Unlike methods involving Hidden Markov Models, this algorithm does not require probability transitions between the models. Among many possible usages of the likelihood, I present a maximum \textit{a posteriori} probability criterion to predict the number of homogeneous segments into which a sequence can be divided, and an application of this method to find CpG islands.

q-bio.QM↗

Silver-staining of proteins in polyacrylamide gels: a general overview

On the basis of the physico-chemical principles underlying silver-staining of proteins, which are recalled in this paper, several methods of silver-staining of proteins after SDS electrophoresis in polyacrylamide gels or isoelectric focusing were tested. The most valuable protocols are presented in this report, including standard methods for unsupported gels and new methods devised for thin (0.5 mm) supported gels for SDS electrophoresis or isoelectric focusing and for staining of small peptides. Generally speaking, the most rapid methods were found to be less sensitive and less reproducible than more time-consuming ones. Among the long methods, those using silver-diammine complex gave the most uniform sensitivity. They require however special home-made gels and cannot be applied to several electrophoretic systems (e.g. systems using tricine or bicine as the trailing ion, or isoelectric focusing in immobilized pH gradients). For these reasons, protocols based on silver nitrate are of a more general use and might be favored. Future trends for silver-staining will also be discussed.

q-bio.GN↗

Qualitative control of periodic solutions in piecewise affine systems; application to genetic networks

Hybrid systems, and especially piecewise affine (PWA) systems, are often used to model gene regulatory networks. In this paper we elaborate on previous work about control problems for this class of models, using also some recent results guaranteeing the existence and uniqueness of limit cycles, based solely on a discrete abstraction of the system and its interaction structure. Our aim is to control the transition graph of the PWA system to obtain an oscillatory behaviour, which is indeed of primary functional importance in numerous biological networks; we show how it is possible to control the appearance or disappearance of a unique stable limit cycle by hybrid qualitative action on the degradation rates of the PWA system, both by static and dynamic feedback, i.e. the adequate coupling of a controlling subnetwork. This is illustrated on two classical gene network modules, having the structure of mixed feedback loops.

math.DS↗

Nucleosome positioning and energetics: Recent advances in genomic and computational studies

Chromatin is a complex of DNA, RNA and proteins whose primary function is to package genomic DNA into the tight confines of a cell nucleus. A fundamental repeating unit of chromatin is the nucleosome, an octamer of histone proteins around which 147 base pairs of DNA are wound in almost two turns of a left-handed superhelix. Chromatin is a dynamic structure which exerts profound influence on regulation of gene expression and other cellular functions. These chromatin-directed processes are facilitated by optimizing nucleosome positions throughout the genome and by remodeling nucleosomes in response to various external and internal signals such as environmental perturbations. Here we discuss large-scale maps of nucleosome positions made available through recent advances in parallel high-throughput sequencing and microarray technologies. We show that these maps reveal common features of nucleosome organization in eukaryotic genomes. We also survey computational models designed to predict nucleosome formation scores or energies, and demonstrate how these predictions can be used to position multiple nucleosome on the genome without steric overlap.

q-bio.GN↗

Resampling Residuals: Robust Estimators of Error and Fit for Evolutionary Trees and Phylogenomics

Phylogenomics, even more so than traditional phylogenetics, needs to represent the uncertainty in evolutionary trees due to systematic error. Here we illustrate the analysis of genome-scale alignments of yeast, using robust measures of the additivity of the fit of distances to tree when using flexi Weighted Least Squares. A variety of DNA and protein distances are used. We explore the nature of the residuals, standardize them, and then create replicate data sets by resampling these residuals. Under the model, the results are shown to be very similar to the conventional sequence bootstrap. With real data they show up uncertainty in the tree that is either due to underestimating the stochastic error (hence massively overestimating the effective sequence length) and/or systematic error. The methods are extended to the very fast BME criterion with similarly promising results.

q-bio.PE↗

Expectation-Maximization (EM) Algorithms for Mapping Short Reads Illustrated with FAIRE data and the TP53-WRAP53 Gene Region

Huge numbers of short reads are being generated for mapping back to the genome to discover the frequency of transcripts, miRNAs, DNAase hypersensitive sites, FAIRE regions, nucleosome occupancy, etc. Since these reads are typically short (e.g., 36 base pairs) and since many eukaryotic genomes, including humans, have highly repetitive sequences then many of these reads map to two or more locations in the genome. Current mapping of these reads, grading them according to 0, 1 or 2 mismatches wastes a great deal of information. These short sequences are typically mapped with no account of the accuracy of the sequence, even in company software when per base error rates are being reported by another part of the machine. Further, multiply mapping locations are frequently discarded altogether or allocated with no regard to where other reads are accumulating. Here we show how to combine probabilistic mapping of reads with an EM algorithm to iteratively improve the empirical likelihood of the allocation of short reads. Mapping using LAST takes into account the per base accuracy of the read, plus insertions and deletions, plus anticipated occasional errors or SNPs with respect to the parent genome. The probabilistic EM algorithm iteratively allocates reads based on the proportion of reads mapping within windows on the previous cycle, along with any prior information on where the read best maps. The methods are illustrated with FAIRE ENCODE data looking at the very important head-to-head gene combination of TP53 and WRAP 53.

q-bio.GN↗

A new method for identifying vertebrates using only their mitochondrial DNA

A new method for determining whether or not a mitrochondrial DNA (mtDNA) sequence belongs to a vertebrate is described and tested. This method only needs the mtDNA sequence of the organism in question, and unlike alignment based methods, it does not require it to be compared with anything else. The method is tested on all 1877 mtDNA sequences that were on NCBI's nucleotide database on August 12, 2009, and works in 94.57% of the cases. Furthermore, all organisms on which this method failed are closely related phylogenetically in comparison to all other organisms included in the study. A list of potential extensions to this method and open problems that emerge out of this study is presented at the end.

q-bio.GN↗

Effectively integrating information content and structural relationship to improve the GO-based similarity measure between proteins

The Gene Ontology (GO) provides a knowledge base to effectively describe proteins. However, measuring similarity between proteins based on GO remains a challenge. In this paper, we propose a new similarity measure, information coefficient similarity measure (SimIC), to effectively integrate both the information content (IC) of GO terms and the structural information of GO hierarchy to determine the similarity between proteins. Testing on yeast proteins, our results show that SimIC efficiently addresses the shallow annotation issue in GO, thus improves the correlations between GO similarities of yeast proteins and their expression similarities as well as between GO similarities of yeast proteins and their sequence similarities. Furthermore, we demonstrate that the proposed SimIC is superior in predicting yeast protein interactions. We predict 20484 yeast protein-protein interactions (PPIs) between 2462 proteins based on the high SimIC values of biological process (BP) and cellular component (CC). Examining the 214 MIPS complexes in our predicted PPIs shows that all members of 159 MIPS complexes can be found in our PPI predictions, which is more than those (120/214) found in PPIs predicted by relative specificity similarity (RSS). Integrating IC and structural information of GO hierarchy can improve the effectiveness of the semantic similarity measure of GO terms. The new SimIC can effectively correct the effect of shallow annotation, and then provide an effective way to measure similarity between proteins based on Gene Ontology.

cs.CE↗

Using Financial Ratios to Identify Romanian Distressed Companies

In the context of the current financial crisis, when more companies are facing bankruptcy or insolvency, the paper aims to find methods to identify distressed firms by using financial ratios. The study will focus on identifying a group of Romanian listed companies, for which financial data for the year 2008 were available. For each company a set of 14 financial indicators was calculated and then used in a principal component analysis, followed by a cluster analysis, a logit model, and a CHAID classification tree.

q-fin.PM↗

DNA-MATRIX a tool for DNA motif discovery and weight matrix construction

In computational molecular biology, gene regulatory binding sites prediction in whole genome remains a challenge for the researchers. Now a days, the genome wide regulatory binding site prediction tools required either direct pattern sequence or weight matrix. Although there are known transcription factor binding sites databases available for genome wide prediction but no tool is available which can construct different weight matrices as per need of user or tools available for large data set scanning by first aligning the input upstream or promoter sequences and than construct the matrices in different level and file format. Considering this, we developed a DNA MATRIX tool for searching putative regulatory binding sites in gene upstream sequences. This tool uses the simple biological rule based heuristic algorithm for weight matrix construction, which can be transformed into different formats after motif alignment and therefore provides the possibility to identify the most potential conserved binding sites in the regulated genes. The user may construct and save specific weight or frequency matrices in different form and file formats based on user based selection of conserved aligned block of short sequences ranges from 6 to 20 base pairs and prior nucleotide frequency before weight scoring.

q-bio.GN↗