Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genome alignment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,441 records · Page 80Linked to original sources
PubMed2003

Amino acid substitutions in the human genome: evolutionary implications of single nucleotide polymorphisms.

Functional differences between amino acids have long been of interest in understanding protein evolution. Several indices exist for comparing residues on the basis of their physicochemical properties and frequencies of occurrence in conserved protein alignments. Here we present a residue dissimilarity index based on coding single nucleotide polymorphisms (SNPs) in the human genome. The index represents an average, organism-wide set of differences between residues and provides important insight into evolutionary restraints on residue substitutions in the human genome. Unlike previous models, it is not restricted to highly conserved protein structures, nor confounded by evolutionary differences between species. Our results confirm earlier observations regarding residue mutabilities but also suggest that in addition to the established key properties, such as size and polarity, charge conservation may be an important and currently underestimated factor in protein evolution. We also estimate that less than 51% of amino acid substitutions occurring in the human genome are evolutionarily neutral.

Amino Acid Substitution↗
PubMed2000

Alfresco--a workbench for comparative genomic sequence analysis.

Comparative analysis of genomic sequences provides a powerful tool for identifying regions of potential biologic function; by comparing corresponding regions of genomes from suitable species, protein coding or regulatory regions can be identified by their homology. This requires the use of several specific types of computational analysis tools. Many programs exist for these types of analysis; not many exist for overall view/control of the results, which is necessary for large-scale genomic sequence analysis. Using Java, we have developed a new visualization tool that allows effective comparative genome sequence analysis. The program handles a pair of sequences from putatively homologous regions in different species. Results from various different existing external analysis programs, such as database searching, gene prediction, repeat masking, and alignment programs, are visualized and used to find corresponding functional sequence domains in the two sequences. The user interacts with the program through a graphic display of the genome regions, in which an independently scrollable and zoomable symbolic representation of the sequences is shown. As an example, the analysis of two unannotated orthologous genomic sequences from human and mouse containing parts of the UTY locus is presented.

Algorithms↗
PubMedDate not supplied

Genomic annotation and transcriptome analysis of the zebrafish (Danio rerio) hox complex with description of a novel member, hox b 13a.

The zebrafish (Danio rerio) is an important model in evolutionary developmental biology, and its study is being revolutionized by the zebrafish genome project. Sequencing is at an advanced stage, but annotation is largely the result of in silico analyses. We have performed genomic annotation, comparative genomics, and transcriptional analysis using microarrays of the hox homeobox-containing transcription factors. These genes have important roles in specifying the body plan. Candidate sequences were located in version Z v 4 of the Ensembl genome database by TBLASTN searching with Danio and other vertebrate published Hox protein sequences. Homologies were confirmed by alignment with reference sequences, and by the relative position of genes along each cluster. RT-PCR using adult Tübingen cDNA was used to confirm annotations, to check the genomic sequence and to confirm expression in vivo. Our RT-PCR and microarray data show that all 49 hox genes are expressed in adult zebrafish. Significant expression for all known hox genes could be detected in our microarray analysis. We also find significant expression of hox 8 paralogs and hox b 7 a in the anti-sense direction. A novel gene, D. rerio hox b 13 a, was identified, and a preliminary characterization by in situ hybridization showed expression at 24 hpf at the tip of the developing tail. We are currently characterizing this gene at the functional level. We argue that the oligo design for microarrays can be greatly enhanced by the availability of genomic sequences.

Animals↗
PubMed2002

PipeOnline 2.0: automated EST processing and functional data sorting.

Expressed sequence tags (ESTs) are generated and deposited in the public domain, as redundant, unannotated, single-pass reactions, with virtually no biological content. PipeOnline automatically analyses and transforms large collections of raw DNA-sequence data from chromatograms or FASTA files by calling the quality of bases, screening and removing vector sequences, assembling and rewriting consensus sequences of redundant input files into a unigene EST data set and finally through translation, amino acid sequence similarity searches, annotation of public databases and functional data. PipeOnline generates an annotated database, retaining the processed unigene sequence, clone/file history, alignments with similar sequences, and proposed functional classification, if available. Functional annotation is automatic and based on a novel method that relies on homology of amino acid sequence multiplicity within GenBank records. Records are examined through a function ordered browser or keyword queries with automated export of results. PipeOnline offers customization for individual projects (MyPipeOnline), automated updating and alert service. PipeOnline is available at http://stress-genomics.org.

Automation↗
PubMed2000

Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot-spot is not elevated above the genome average rate.

An increasing number of human diseases and syndromes are being found to result from micro-duplications or microdeletions arising from meiotic recombination between homologous repeats on the same chromosome. The first microduplication syndrome delineated, Charcot-Marie-Tooth disease type 1A (CMT1A), results from unequal crossing over between two >98% identical 24 kb repeats (CMT1A-REPs) on chromosome 17. In addition to its medical significance, the CMT1A region has features that make it a unique resource for detailed analysis of human unequal recombination. Previous studies of CMT1A patients showed that the majority of unequal crossovers occurred within a small region (<1 kb) of the REPs suggesting the presence of a recombination hot-spot. We directly measured the frequency of unequal recombination in the hot-spot region using sperm from four normal individuals. Surprisingly, unequal recombination between the REPs occurs at a rate no greater than the average rate for the male genome (approximately 1 cM/Mb) and is the same as that expected for equally aligned REPs. This conclusion extends to humans the findings in yeast that recombination between repeated sequences far apart on the same chromosome may occur at similar frequencies to allelic recombination. Finally, the CMT1A hot-spot stands in sharp contrast to the human MS32 mini-satellite-associated hot-spot that exhibits highly enhanced recombination initiation in addition to positional specificity. One possibility is that the CMT1A hot-spot may consist of a region with genome average recombination potential embedded within a recombination cold-spot.

Adult↗
PubMed1999

Genome analysis: Assigning protein coding regions to three-dimensional structures.

We describe the results of a procedure for maximizing the number of sequences that can be reliably linked to a protein of known three-dimensional structure. Unlike other methods, which try to increase sensitivity through the use of fold recognition software, we only use conventional sequence alignment tools, but apply them in a manner that significantly increases the number of relationships detected. We analyzed 11 genomes and found that, depending on the genome, between 23 and 32% of the ORFs had significant matches to proteins of known structure. In all cases, the aligned region consisted of either >100 residues or >50% of the smaller sequence. Slightly higher percentages could be attained if smaller motifs were also included. This is significantly higher than most previously reported methods, even those that have a fold-recognition component. We survey the biochemical and structural characteristics of the most frequently occurring proteins, and discuss the extent to which alignment methods can realistically assign function to gene products.

Algorithms↗
PubMed2004

PathAligner: metabolic pathway retrieval and alignment.

MOTIVATION: Analysis of metabolic pathways is a central topic in understanding the relationship between genotype and phenotype. The rapid accumulation of biological data provides the possibility of studying metabolic pathways at both the genomic and the metabolic levels. Retrieving metabolic pathways from current biological data sources, reconstructing metabolic pathways from rudimentary pathway components, and aligning metabolic pathways with each other are major tasks. Our motivation was to develop a conceptual framework and computational system that allows the retrieval of metabolic pathway information and the processing of alignments to reveal the similarities between metabolic pathways. RESULTS: PathAligner extracts metabolic information from biological databases via the Internet and builds metabolic pathways with data sources of genes, sequences, enzymes, metabolites etc. It provides an easy-to-use interface to retrieve, display and manipulate metabolic information. PathAligner also provides an alignment method to compare the similarity between metabolic pathways. AVAILABILITY: PathAligner is available at http://bibiserv.techfak.uni-bielefeld.de/pathaligner.

Algorithms↗
PubMed1994

Deriving non-homogeneous DNA Markov chain models by cluster analysis algorithm minimizing multiple alignment entropy.

Non-homogeneous Markov chain models can represent biologically important regions of DNA sequences. The statistical pattern that is described by these models is usually weak and was found primarily because of strong biological indications. The general method for extracting similar patterns is presented in the current paper. The algorithm incorporates cluster analysis, multiple alignment and entropy minimization. The method was first tested using the set of DNA sequences produced by Markov chain generators. It was shown that artificial gene sequences, which initially have been randomly set up along the multiple alignment panels, are aligned according to the hidden triplet phase. Then the method was applied to real protein-coding sequences and the resulting alignment clearly indicated the triplet phase and produced the parameters of the optimal 3-periodic non-homogeneous Markov chain model. These Markov models were already employed in the GeneMark gene prediction algorithm, which is used in genome sequencing projects. The algorithm can also handle the case in which the sequences to be aligned reveal different statistical patterns, such as Escherichia coli protein-coding sequences belonging to Class II and Class III. The algorithm accepts a random mix of sequences from different classes, and is able to separate them into two groups (clusters), align each cluster separately, and define a non-homogeneous Markov chain model for each sequence cluster.

Algorithms↗
PubMed2005

Discovery of novel conserved peptide domains by ortholog comparison within plant multi-protein families.

Assigning individual functions to the proteins encoded by the genome of the dicotyledonous reference species Arabidopsis thaliana is one of the major challenges in current plant molecular biology. Frequently, Arabidopsis protein families are biocomputationally analyzed by multiple amino acid sequence alignments of the respective family members for detection of conserved peptide motifs that might be of functional relevance. Mere sequence alignment of paralogous sequences may obscure amino acid patches that are highly conserved amongst orthologs and thus potentially relevant for isoform-specific protein function(s). Here I exemplarily illustrate this potential pitfall by amino acid sequence alignments of the heptahelical MLO proteins using either the suite of 15 isoforms (paralogs) encoded by the Arabidopsis genome or a collection of 13 ortholog sequences derived from a set of both monocotyledonous and dicotyledonous plant species. The findings are corroborated by an analogous analysis of the distinct plant multi-protein family of CONSTANS-like transcription regulators. The data reveal that the generally higher sequence similarity of orthologs versus paralogs is not uniformly distributed among the amino acid positions of the orthologs but at least partially clustered in distinct sites/domains, suggesting conservation of isoform-specific functional modules across taxa.

Amino Acid Sequence↗
PubMed2006

Phylogenetic reconstruction of orthology, paralogy, and conserved synteny for dog and human.

Accurate predictions of orthology and paralogy relationships are necessary to infer human molecular function from experiments in model organisms. Previous genome-scale approaches to predicting these relationships have been limited by their use of protein similarity and their failure to take into account multiple splicing events and gene prediction errors. We have developed PhyOP, a new phylogenetic orthology prediction pipeline based on synonymous rate estimates, which accurately predicts orthology and paralogy relationships for transcripts, genes, exons, or genomic segments between closely related genomes. We were able to identify orthologue relationships to human genes for 93% of all dog genes from Ensembl. Among 1:1 orthologues, the alignments covered a median of 97.4% of protein sequences, and 92% of orthologues shared essentially identical gene structures. PhyOP accurately recapitulated genomic maps of conserved synteny. Benchmarking against predictions from Ensembl and Inparanoid showed that PhyOP is more accurate, especially in its predictions of paralogy. Nearly half (46%) of PhyOP paralogy predictions are unique. Using PhyOP to investigate orthologues and paralogues in the human and dog genomes, we found that the human assembly contains 3-fold more gene duplications than the dog. Species-specific duplicate genes, or "in-paralogues," are generally shorter and have fewer exons than 1:1 orthologues, which is consistent with selective constraints and mutation biases based on the sizes of duplicated genes. In-paralogues have experienced elevated amino acid and synonymous nucleotide substitution rates. Duplicates possess similar biological functions for either the dog or human lineages. Having accounted for 2,954 likely pseudogenes and gene fragments, and after separating 346 erroneously merged genes, we estimated that the human genome encodes a minimum of 19,700 protein-coding genes, similar to the gene count of nematode worms. PhyOP is a fast and robust approach to orthology prediction that will be applicable to whole genomes from multiple closely related species. PhyOP will be particularly useful in predicting orthology for mammalian genomes that have been incompletely sequenced, and for large families of rapidly duplicating genes.

Animals↗
PubMed1999

Pathway alignment: application to the comparative analysis of glycolytic enzymes.

Comparative analysis of metabolic pathways in different genomes yields important information on their evolution, on pharmacological targets and on biotechnological applications. In this study on glycolysis, three alternative ways of comparing biochemical pathways are combined: (1) analysis and comparison of biochemical data, (2) pathway analysis based on the concept of elementary modes, and (3) a comparative genome analysis of 17 completely sequenced genomes. The analysis reveals a surprising plasticity of the glycolytic pathway. Isoenzymes in different species are identified and compared; deviations from the textbook standard are detailed. Several potential pharmacological targets and by-passes (such as the Entner-Doudoroff pathway) to glycolysis are examined and compared in the different species. Archaean, bacterial and parasite specific adaptations are identified and described.

Enzymes↗
PubMed2002

ProDom: automated clustering of homologous domains.

The ProDom database is a comprehensive set of protein domain families automatically generated from the SWISS-PROT and TrEMBL sequence databases. An associated database, ProDom-CG, has been derived as a restriction of ProDom to completely sequenced genomes. The ProDom construction method is based on iterative PSI-BLAST searches and multiple alignments are generated for each domain family. The ProDom web server provides the user with a set of tools to visualise multiple alignments, phylogenetic trees and domain architectures of proteins, as well as a BLAST-based server to analyse new sequences for homologous domains. The comprehensive nature of ProDom makes it particularly useful to help sustain the growth of InterPro.

Databases, Protein↗
PubMed1993

Cloning and sequence analysis of the glucoamylase gene of Neurospora crassa.

A 1.0-kb DNA fragment, corresponding to an internal region of the Neurospora crassa glucoamylase gene, gla-1, was generated from genomic DNA by the polymerase chain reaction, using oligonucleotide primers which had been deduced from the known N-terminal amino-acid sequence or from consensus regions within the aligned amino-acid sequences of other fungal glucoamylases. The fragment was used to screen an N. crassa genomic DNA library. One clone contained the gene together with flanking regions and its sequence was determined. The gene was found to code for a preproprotein of 626 amino acids, 35 of which constitute a signal and propeptide region. The protein and the gene are compared with corresponding sequences in other fungi.

Amino Acid Sequence↗
PubMed2006

Developments in CORG: a gene-centric comparative genomics resource.

The CORG resource (Comparative Regulatory Genomics, http://corg.eb.tuebingen.mpg.de) provides extensive cross-species comparisons of promoter regions in particular and whole gene loci in general. Pairwise as well as multiple alignments of 10 vertebrate species form the key component of CORG. We implemented a rapid alignment approach based on weight matrix motif anchors to ensure efficient computation and biologically informative alignments. All CORG workbench components have been enhanced towards more flexibility and interactivity. Reference sequence based data presentation and analysis was put into the well-known and modular Generic Genome Browser framework. Herein, various plugins facilitate online data analysis and integration with static conservation data. Main emphasis was put on the design of a new JAVA WebStart application for comparative data display. Flexible data import and export options for standard formats complete the provided services.

Animals↗
PubMed2006

The amelogenin story: origin and evolution.

Genome sequencing and gene mapping have permitted the identification of HEVIN (SPARC-Like1) as the probable ancestor of the enamel matrix proteins (EMPs), amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM). We have undertaken a phylogenetic analysis to elucidate their relationships. AMEL genes available in databases, and new sequences obtained in blast searching genomes or expressed sequence tags, were compiled (22 full-length sequences), aligned, and the ancestral sequence calculated and used to search for similarities using psi-blast. Hits were obtained with the N-terminal region of AMBN, ENAM, and HEVIN. We retrieved all available AMBN (n=8), ENAM (n=3), and HEVIN (n=4) sequences. The sequences of the four proteins were aligned and analyzed phylogenetically. AMEL and AMBN are sister genes, which diverged after duplication of a common ancestor issued from ENAM. The latter derived from a copy of HEVIN. Comparisons of gene organization, amino acid sequences and location of ENAM and AMBN, adjacent on the same chromosome, suggest that AMBN is closer to ENAM than AMEL. This supports AMEL as being derived from AMBN duplication. This duplication occurred long before tetrapod differentiation, probably in an ancestral osteichthyan. The story of AMEL origin is completed as follows: SPARC-->HEVIN-->ENAM-->AMBN-->AMEL.

Amelogenin↗
PubMed2004

Pegasys: software for executing and integrating analyses of biological sequences.

BACKGROUND: We present Pegasys--a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools. RESULTS: The Pegasys system includes numerous tools for pair-wise and multiple sequence alignment, ab initio gene prediction, RNA gene detection, masking repetitive sequences in genomic DNA as well as filters for database formatting and processing raw output from various analysis tools. We introduce a novel data structure for creating workflows of sequence analyses and a unified data model to store its results. The software allows users to dynamically create analysis workflows at run-time by manipulating a graphical user interface. All non-serial dependent analyses are executed in parallel on a compute cluster for efficiency of data generation. The uniform data model and backend relational database management system of Pegasys allow for results of heterogeneous programs included in the workflow to be integrated and exported into General Feature Format for further analyses in GFF-dependent tools, or GAME XML for import into the Apollo genome editor. The modularity of the design allows for new tools to be added to the system with little programmer overhead. The database application programming interface allows programmatic access to the data stored in the backend through SQL queries. CONCLUSIONS: The Pegasys system enables biologists and bioinformaticians to create and manage sequence analysis workflows. The software is released under the Open Source GNU General Public License. All source code and documentation is available for download at http://bioinformatics.ubc.ca/pegasys/.

Computational Biology↗
PubMed1998

A strategy for finding regions of similarity in complete genome sequences.

MOTIVATION: Complete genomic sequences will become available in the future. New methods to deal with very large sequences (sizes beyond 100 kb) efficiently are required. One of the main aims of such work is to increase our understanding of genome organization and evolution. This requires studies of the locations of regions of similarity. RESULTS: We present here a new tool, ASSIRC ('Accelerated Search for SImilarity Regions in Chromosomes'), for finding regions of similarity in genomic sequences. The method involves three steps: (i) identification of short exact chains of fixed size, called 'seeds', common to both sequences, using hashing functions; (ii) extension of these seeds into putative regions of similarity by a 'random walk' procedure; (iii) final selection of regions of similarity by assessing alignments of the putative sequences. We used simulations to estimate the proportion of regions of similarity not detected for particular region sizes, base identity proportions and seed sizes. This approach can be tailored to the user's specifications. We looked for regions of similarity between two yeast chromosomes (V and IX). The efficiency of the approach was compared to those of conventional programs BLAST and FASTA, by assessing CPU time required and the regions of similarity found for the same data set. AVAILABILITY: Source programs are freely available at the following address: ftp://ftp.biologie.ens. fr/pub/molbio/assirc.tar.gz CONTACT: vincens@biologie.ens.fr, hazout@urbb.jussieu.fr

Algorithms↗
PubMed2005

Haplotype reconstruction from SNP fragments by minimum error correction.

MOTIVATION: Haplotype reconstruction based on aligned single nucleotide polymorphism (SNP) fragments is to infer a pair of haplotypes from localized polymorphism data gathered through short genome fragment assembly. An important computational model of this problem is the minimum error correction (MEC) model, which has been mentioned in several literatures. The model retrieves a pair of haplotypes by correcting minimum number of SNPs in given genome fragments coming from an individual's DNA. RESULTS: In the first part of this paper, an exact algorithm for the MEC model is presented. Owing to the NP-hardness of the MEC model, we also design a genetic algorithm (GA). The designed GA is intended to solve large size problems and has very good performance. The strength and weakness of the MEC model are shown using experimental results on real data and simulation data. In the second part of this paper, to improve the MEC model for haplotype reconstruction, a new computational model is proposed, which simultaneously employs genotype information of an individual in the process of SNP correction, and is called MEC with genotype information (shortly, MEC/GI). Computational results on extensive datasets show that the new model has much higher accuracy in haplotype reconstruction than the pure MEC model.

Algorithms↗