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At least 235 records · Page 13Linked to original sources
PubMed2001

Pruned median networks: a technique for reducing the complexity of median networks.

Observations from molecular marker studies on recently diverged species indicate that substitution patterns in DNA sequences can often be complex and poorly described by tree-like bifurcating evolutionary models. These observations might result from processes of species diversification and/or processes of sequence evolution that are not tree-like. In these cases, bifurcating tree representations provide poor visualization of phylogenetic signals in sequence data. In this paper, we use median networks to study DNA sequence substitution patterns in plant nuclear and chloroplast markers. We describe how to prune median networks to obtain so called pruned median networks. These simpler networks may help to provide a useful framework for investigating the phylogenetic complexity of recently diverged taxa with hybrid origins.

Base Sequence↗
PubMed2004

Predicting protein-peptide interactions via a network-based motif sampler.

MOTIVATION: Many protein-protein interactions are mediated by peptide recognition modules (PRMs), compact domains that bind to short peptides, and play a critical role in a wide array of biological processes. Recent experimental protein interaction data provide us with an opportunity to examine whether we may explain, or even predict their interactions by computational sequence analysis. Such a question was recently posed by the use of random peptide screens to characterize the ligands of one such PRM, the SH3 domain. RESULTS: We describe a general computational procedure for identifying the ligand peptides of PRMs by combining protein sequence information and observed physical interactions into a simple probabilistic model and from it derive an interaction-mediated de novo motif-finding framework. Using a recent all-versus-all yeast two-hybrid SH3 domain interaction network, we demonstrate that our technique can be used to derive independent predictions of interactions mediated by SH3 domains. We show that only when sequence information is combined with such all versus all protein interaction datasets, are we capable of identifying motifs with sufficient sensitivity and specificity for predicting interactions. The algorithm is general so that it may be applied to other PRM domains (e.g. SH2, WW, PDZ). AVAILABILITY: The Netmotsa software and source code, as part of a general Gibbs motif sampling library, are available at http://sf.net/projects/netmotsa

Algorithms↗
PubMed2002

Characterization of three maize bacterial artificial chromosome libraries toward anchoring of the physical map to the genetic map using high-density bacterial artificial chromosome filter hybridization.

Three maize (Zea mays) bacterial artificial chromosome (BAC) libraries were constructed from inbred line B73. High-density filter sets from all three libraries, made using different restriction enzymes (HindIII, EcoRI, and MboI, respectively), were evaluated with a set of complex probes including the 185-bp knob repeat, ribosomal DNA, two telomere-associated repeat sequences, four centromere repeats, the mitochondrial genome, a multifragment chloroplast DNA probe, and bacteriophage lambda. The results indicate that the libraries are of high quality with low contamination by organellar and lambda-sequences. The use of libraries from multiple enzymes increased the chance of recovering each region of the genome. Ninety maize restriction fragment-length polymorphism core markers were hybridized to filters of the HindIII library, representing 6x coverage of the genome, to initiate development of a framework for anchoring BAC contigs to the intermated B73 x Mo17 genetic map and to mark the bin boundaries on the physical map. All of the clones used as hybridization probes detected at least three BACs. Twenty-two single-copy number core markers identified an average of 7.4 +/- 3.3 positive clones, consistent with the expectation of six clones. This information is integrated into fingerprinting data generated by the Arizona Genomics Institute to assemble the BAC contigs using fingerprint contig and contributed to the process of physical map construction.

Blotting, Southern↗
PubMed1998

In situ hybridization analysis of immunoglobulin heavy chain variable gene expression with family specific oligonucleotide probes.

We have developed an improved in situ hybridization (ISH) technique for the analysis of human immunoglobulin heavy chain variable (V(H)) gene family expression in suspensions of human B lymphocytes. Oligonucleotide probes specific for framework region (FR) consensus germline sequences for each of the seven human V(H) gene families were designed and hybridization conditions were developed to accommodate the greatest degree of V(H) gene variation, maximize the sensitivity of transcript detection, and assure the specificity of the technique. The hybridization parameters were rigorously characterized by Southern hybridization to a panel of 30 V(H) cDNA clones and by ISH to 17 B cell lines expressing characterized V(H) genes. Results obtained with ISH using V(H) gene family and isotype-specific gene probes correlated well with histochemical measures of Ig gene product expression. Profiles of cellular V(H) gene expression were generated for mitogen stimulated peripheral blood B lymphocytes from six normal subjects. When compared with estimates of frequency of V(H) genes in the human germline, the results were consistent with a random pattern of V(H) family utilization.

Autoradiography↗
PubMed2006

Decoding non-unique oligonucleotide hybridization experiments of targets related by a phylogenetic tree.

MOTIVATION: The reliable identification of presence or absence of biological agents ("targets"), such as viruses or bacteria, is crucial for many applications from health care to biodiversity. If genomic sequences of targets are known, hybridization reactions between oligonucleotide probes and targets performed on suitable DNA microarrays will allow to infer presence or absence from the observed pattern of hybridization. Targets, for example all known strains of HIV, are often closely related and finding unique probes becomes impossible. The use of non-unique oligonucleotides with more advanced decoding techniques from statistical group testing allows to detect known targets with great success. Of great relevance, however, is the problem of identifying the presence of previously unknown targets or of targets that evolve rapidly. RESULTS: We present the first approach to decode hybridization experiments using non-unique probes when targets are related by a phylogenetic tree. Using a Bayesian framework and a Markov chain Monte Carlo approach we are able to identify over 94% of known targets and assign up to 70% of unknown targets to their correct clade in hybridization simulations on biological and simulated data. AVAILABILITY: Software implementing the method described in this paper and datasets are available from http://algorithmics.molgen.mpg.de/probetrees.

Algorithms↗
PubMedDate not supplied

A human genome map of comparative anchor tagged sequences.

Effective comparative mapping inference utilizing developing gene maps of animal species requires the inclusion of anchored reference loci that are homologous to genes mapped in the more "gene-dense" mouse and human maps. Nominated anchor loci, termed comparative anchor tagged sequences (CATS), have been ordered in the mouse linkage map, but due to the dearth of common polymorphisms among human coding genes have not been well represented in human linkage maps. We present here an ordered framework map of 314 comparative anchor markers in humans based on mapping analysis in the Genebridge 4 panel of radiation hybrid cell lines, plus empirically optimized CATS PCR primers which detect these markers. The ordering of these homologous gene markers in human and mouse maps provides a framework for comparative gene mapping of representative mammalian species.

Animals↗
PubMed1991

Molecular characterization of a major nephritogenic domain in the autoantigen of anti-tubular basement membrane disease.

Anti-tubular basement membrane (alpha TBM) disease is a form of primary interstitial nephritis mediated by autoimmune T cells and alpha TBM antibodies. In mice and humans the nephritogenic immune response is directed to a glycoprotein (3M-1) found along the proximal tubule of the kidney. We have isolated cDNAs from an expression library that encodes for the common framework domain of the 3M-1 antigen. This common domain was once related evolutionarily to a family of intermediate filament-associated proteins. Northern hybridization revealed that all isoforms of 3M-1 range between 1700 and 1900 base pairs and in situ hybridization studies indicate that transcripts are found in tubular epithelium. Candidate peptide fragments were deduced and synthesized from the sequence encoding this common framework domain, and one of the peptide residues was able to bind a monoclonal 3M-1-reactive alpha TBM antibody, stimulate the growth of 3M-1-reactive helper T cells, and induce nephritogenic effector T cells capable of producing interstitial nephritis. Our results indicate that a unique, immunodominant region of the 3M-1 antigen is an informative participant in the emergence of autoimmune injury to certain basement membranes.

Amino Acid Sequence↗
PubMed1993

Oligonucleotide probes to the 5' end of the framework 3 (FR3) gene segment detect polymorphisms of VH gene sequences encoding biologically important amino acid residues.

In this study, we demonstrate the use of oligonucleotide probes to the most VH family-specific framework, the Framework 3 (FR3) gene segment, in the analysis of germline DNA. Compared with the hybridization of restriction enzyme-digested genomic DNA to large, cloned human VH family probes, hybridization with oligonucleotides derived from nucleotides 199 to 258 of the FR3 gene segments both yields less complex patterns and highlights polymorphic variations between individuals. The potentially important role played by amino acid residues encoded by the FR3 gene segment in influencing conformation, antigen binding and affinity of the physically proximal complementarity determining regions (CDRs) suggests FR3 sequence conservation to be biologically significant. Genomic studies combining information from both CDR and framework restriction fragment polymorphisms can prove useful in detecting specific genes and in identifying haplotypes of interest.

Genes, Immunoglobulin↗
PubMed2000

Genomic structure, chromosomal localization and expression of the human LIM-homeobox gene LHX5.

The LIM-homeobox gene Lhx5 plays an essential role in the regulation of neuronal differentiation and migration during development of the central nervous system. Mice lacking Lhx5 function show severely disorganized brain morphology and are impaired in cognition and motor coordination. In this study, we characterized the cDNA and genomic organization of the human LHX5 gene and analyzed its expression and chromosomal location. The human gene was found to contain five exons encoding a protein composed of 402 amino acids that is 98.8% identical to mouse Lhx5. By reverse transcriptase polymerase chain reaction, LHX5 transcripts were detected in fetal brain and in various regions of the adult central nervous system including the spinal cord, the thalamus, and the cerebellum. Fluorescence in situ hybridization mapped the LHX5 gene to chromosome 12, position 12q24.31-24.32. These results provide a framework for future analysis of possible association of human hereditary disorders with mutations in LHX5.

Amino Acid Sequence↗
PubMed1999

The standard model of T-cell receptor function: a critical reassessment.

The Standard Model of T-cell receptor (TCR) function is the distillation of many views. Here we provide a summary that is intended to capture the flavour of the whole, without assigning particular blame, or credit, to any one part. The Standard Model is based on the notion of a single TCR-combining site that sums the binding contributions of MHC and peptide to produce a single signal to the T cell. How this signal is interpreted can vary with the state of the T cell. A growing number of creaks in the tweaks needed to maintain the Standard Model suggest that it may be timely to make a critical reassessment of the facts and their interpretation. The result of this effort has been to uncover a long-overlooked fact that T cells do not recognize hybrid class II major histocompatibility complex alleles; they recognize only those haplotypes directly associated with each alpha- or beta- subunit of class II. Our attempts to tweak the Standard Model to deal with lack of recognition of hybrid class II alleles led us, by surprise, to a quite different framework with which to view TCR function.

Animals↗
PubMed1986

Structural differences in a single gene encoding the V kappa Ser group of light chains explain the existence of two mouse light-chain genetic markers.

Two phenotypic markers of mouse immunoglobulin kappa light chains, the IB-peptide marker and the Ef1a isoelectric focusing marker, are expressed by the C58/J, AKR/J, RF/J, and PL/J strains (called expressor strains) but not by BALB/c and most inbred strains. Expression is linked to the kappa light-chain locus and the Lyt-2/Lyt-3 genes on chromosome 6. Light chains bearing these markers belong to a group of variable region kappa chain (V kappa) regions called V kappa Ser, which has a serine amino terminus and a framework 1 region not observed to date among BALB/c light chains. Southern hybridization of genomic DNA with a V kappa Ser-specific cDNA probe has demonstrated a single strongly hybridizing DNA fragment in all strains of mice tested. Characteristic restriction enzyme polymorphisms define the V kappa Ser alleles of expressor (Igk-VSera) and nonexpressor (Igk-VSerb) strains. In the present study, the unrearranged V kappa Ser gene and its flanking regions from an expressor (C.C58) and nonexpressor (BALB/c) strain have been cloned and their nucleotide sequences determined. The C.C58 V kappa Ser gene isolated (the Igk-VSera allele) was shown to code for the two phenotypic markers described. While the nucleotide sequence of the BALB/c coding region (the Igk-VSerb allele) shows 97% identity with the C.C58 gene, single nucleotide substitutions lead to structural changes in the encoded protein which render it IB-negative and Ef1a-negative. These differences alone can explain the failure of strains containing the BALB/c allele to express these kappa-chain phenotypic markers. Also, the BALB/c gene contains a single substitution in a conserved octamer sequence approximately equal to 100 nucleotides upstream of the coding region, which could affect its expression. Finally, the C.C58 allele contains a BAM5/R repetitive DNA element approximately equal to 1200 nucleotides upstream of the coding regions that is not present in BALB/c. This element gives rise to the EcoRI and BamHI restriction enzyme polymorphisms, which distinguish the Igk-VSera and Igk-VSerb alleles.

Amino Acid Sequence↗
PubMed2002

A model-based method for identifying species hybrids using multilocus genetic data.

We present a statistical method for identifying species hybrids using data on multiple, unlinked markers. The method does not require that allele frequencies be known in the parental species nor that separate, pure samples of the parental species be available. The method is suitable for both markers with fixed allelic differences between the species and markers without fixed differences. The probability model used is one in which parentals and various classes of hybrids (F(1)'s, F(2)'s, and various backcrosses) form a mixture from which the sample is drawn. Using the framework of Bayesian model-based clustering allows us to compute, by Markov chain Monte Carlo, the posterior probability that each individual belongs to each of the distinct hybrid classes. We demonstrate the method on allozyme data from two species of hybridizing trout, as well as on two simulated data sets.

Animals↗
PubMed2001

Toward integration of comparative genetic, physical, diversity, and cytomolecular maps for grasses and grains, using the sorghum genome as a foundation.

The small genome of sorghum (Sorghum bicolor L. Moench.) provides an important template for study of closely related large-genome crops such as maize (Zea mays) and sugarcane (Saccharum spp.), and is a logical complement to distantly related rice (Oryza sativa) as a "grass genome model." Using a high-density RFLP map as a framework, a robust physical map of sorghum is being assembled by integrating hybridization and fingerprint data with comparative data from related taxa such as rice and using new methods to resolve genomic duplications into locus-specific groups. By taking advantage of allelic variation revealed by heterologous probes, the positions of corresponding loci on the wheat (Triticum aestivum), rice, maize, sugarcane, and Arabidopsis genomes are being interpolated on the sorghum physical map. Bacterial artificial chromosomes for the small genome of rice are shown to close several gaps in the sorghum contigs; the emerging rice physical map and assembled sequence will further accelerate progress. An important motivation for developing genomic tools is to relate molecular level variation to phenotypic diversity. "Diversity maps," which depict the levels and patterns of variation in different gene pools, shed light on relationships of allelic diversity with chromosome organization, and suggest possible locations of genomic regions that are under selection due to major gene effects (some of which may be revealed by quantitative trait locus mapping). Both physical maps and diversity maps suggest interesting features that may be integrally related to the chromosomal context of DNA-progress in cytology promises to provide a means to elucidate such relationships. We seek to provide a detailed picture of the structure, function, and evolution of the genome of sorghum and its relatives, together with molecular tools such as locus-specific sequence-tagged site DNA markers and bacterial artificial chromosome contigs that will have enduring value for many aspects of genome analysis.

DNA Fingerprinting↗
PubMed2004

Assigning cells to switches in cellular networks by incorporating a pricing mechanism into simulated annealing.

Handoff and cabling costs play key roles in the design of cellular telecommunications networks. Efficient homing of cells to switches can have a significant impact on each of these costs. In the presence of capacity constraints at the switches, the problem of assigning cells to switches becomes a difficult one to solve, with all effective solution approaches being based on heuristic techniques. This paper presents a hybrid heuristic which integrates ideas from linear programming into a simulated annealing framework. Extensive computational results are presented comparing the performance of the heuristic with the lower bound obtained from the linear programming relaxation. These results indicate that this price influenced simulated annealing (PISA) procedure is extremely efficient, usually providing solutions with gaps around 1% in less than 1 s.

Journal Article↗
PubMed1997

From long range mapping to sequence-ready contigs on human chromosome 6.

Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. The strategy we are following involves establishing a high density framework map of the order of 15 markers per Megabase using radiation hybrid (RH) mapping. The markers are then used to identify large-insert genomic bacterial clones covering the chromosome, which are assembled into sequence-ready contigs by restriction enzyme fingerprinting and sequence tagged site (STS) content analysis. Contig gap closure is performed by walking experiments using STSs developed from the end sequences of the clone inserts.

Chromosomes, Human, Pair 6↗
PubMed2006

From local hybrid functionals to "localized local hybrid" potentials: formalism and thermochemical tests.

Hybrid exchange-correlation functionals with position-dependent exact-exchange admixture (local hybrid functionals) have been implemented self-consistently for the first time. Functional derivatives with respect to the occupied orbitals have been derived and were subsequently transformed into local and multiplicative potentials within the framework of the optimized effective potential. The resulting local and multiplicative Kohn-Sham potentials are termed "localized local hybrid" (LLH) potentials. They have been evaluated in calculations of atomization energies for a series of main-group molecules. It is shown that LLH potentials yield somewhat better thermochemical results than non-self-consistent post-GGA calculations with the same local hybrid energy functionals for orbitals obtained with a different potential. The choice of the "local mixing function" (LMF) is discussed. This is the key quantity for the performance of local hybrid functionals that determines the amount of exact-exchange admixture at a given point in space. Careful analyses of average exact-exchange admixtures and of the spatial variation of two different LMFs for various molecules provide insight into the shortcomings of the currently used local hybrid functionals. Beyond a too large average exact-exchange admixture, both LMFs used appear to provide an unbalanced description of exact-exchange admixture across bonds to hydrogen. LLH potentials open the way for property calculations with local hybrid functionals.

Journal Article↗