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Biomedical subjects

A Grigoriev

Publications and source records attributed to A Grigoriev.

12 recordsLinked to original sources

Strand-specific compositional asymmetries in double-stranded DNA viruses.

Analysis of 22 complete sequences of double-stranded DNA viruses reveals striking compositional asymmetries between leading and lagging, and between transcribed and non-transcribed strands. In all bi-directionally replicated genomes analyzed, the observed leading strand GC skew (measuring relative excess of guanines versus cytosines) is different from that in the lagging strand. In most of these genomes GC skew switches polarity close to replication origins. GC skew changes linearly across adenovirus linear genomes, which replicate from one end. In papillomavirus, GC skew is positive in one half of the genome where transcription and replication proceed in the same direction, and is close to zero in the other half with divergent transcription and replication. Possible contributions of these two processes (and associated repair mechanisms) as well as other potential sources of strand bias in the observed asymmetries are discussed. Use of cumulative skew plots for genome comparisons is demonstrated on the example of herpes simplex virus.

Adenoviruses, Human

Analyzing genomes with cumulative skew diagrams.

A novel method of cumulative diagrams shows that the nucleotide composition of a microbial chromosome changes at two points separated by about a half of its length. These points coincide with sites of replication origin and terminus for all bacteria where such sites are known. The leading strand is found to contain more guanine than cytosine residues. This fact is used to predict origin and terminus locations in other bacterial and archaeal genomes. Local changes, visible as diagram distortions, may represent recent genome rearrangements, as demonstrated for two strains of Escherichia coli . Analysis of the diagrams of viral and mitochondrial genomes suggests a link between the base composition bias and the time spent by DNA in a single stranded state during replication.

Bacteria

IXDB, an X chromosome integrated database.

The integrated X chromosome database (IXDB) is a repository for physical mapping data of the human X chromosome. Its current content is the result of a strict integration of data stemming from many different sources. The main features of IXDB include a flexible and extendible schema, a comfortable and fully cross-referenced WWW interface (http://ixdb.mpimg-berlin-dahlem.mpg.de ) and a graphical map viewer implemented in JAVA. The database stores objects used in physical mapping as well as the maps resulting from this work, but a strong emphasis is placed on recording experiments that connect objects together. This should greatly contribute to fulfilling one of the major goals of the database: to support the construction of an integrated physical, genetic, transcript and sequence map of the human X chromosome.

Chromosome Mapping

A distributed environment for physical map construction.

MOTIVATION: With the main focus of the Human Genome Project shifting to sequencing, bioinformatics support for constructing large-scale genomic maps of other organisms is still required. We attempt to provide for this with our work, aimed at the delivery of robust and user-friendly contig-building software on the WWW. RESULTS: We present a prototype distributed analytical environment for molecular biologists working in the area of genomic mapping. It consists of the WWW server for constructing contigs from users' data with a hypertext output connected to Java-based map visualization software. AVAILABILITY: Freely available on http://www.mpimg-berlin-dahlem.mpg. de/ approximately andy/server/ CONTACT: andy@rag3.rz-berlin.mpg.de

Algorithms

Reusable graphical interface to genome information resources.

This paper describes a prototype genome display and query system for the World Wide Web, which could play the role of a graphical interactive gateway to online genome information services. It provides a uniform interface to display mapping and sequencing data for the human, mouse and yeast genomes and could be easily extended to accommodate more information as it becomes available. This system uses a Java applet, DerBrowser, for delivering interactive content to an end user. The architecture and functionality of this applet are described, with respect to views of both users and data providers.

Animals

Genomes with a view.

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Computer Communication Networks

A radiation hybrid map spanning the entire human X chromosome integrating YACs, genes, and STS markers.

We present a radiation hybrid (RH) map of human Chromosome (Chr) X, using 50 markers on 72 radiation hybrids. The markers, obtained from the consensus map, form a grid spanning the entire chromosome. To check the RH map, the marker order was determined by analysis of presence or absence of retained human DNA fragments in the RHs; the comparison with the consensus showed a similar order. Any STSs, microsatellites, genes, and clones can be positioned and ordered relative to the marker grid. This approach integrates genetic, physical, and large-scale clone mapping and is used to link YAC contigs containing data from various experimental sources.

Chromosome Mapping

An integrated YAC map of the human X chromosome.

The human X chromosome is associated with a large number of disease phenotypes, principally because of its unique mode of inheritance that tends to reveal all recessive disorders in males. With the longer term goal of identifying and characterizing most of these genes, we have adopted a chromosome-wide strategy to establish a YAC contig map. We have performed > 3250 inter Alu-PCR product hybridizations to identify overlaps between YAC clones. Positional information associated with many of these YAC clones has been derived from our Reference Library Database and a variety of other public sources. We have constructed a YAC contig map of the X chromosome covering 125 Mb of DNA in 25 contigs and containing 906 YAC clones. These contigs have been verified extensively by FISH and by gel and hybridization fingerprinting techniques. This independently derived map exceeds the coverage of recently reported X chromosome maps built as part of whole-genome YAC maps.

Chromosome Mapping

An algorithm to detect chimeric clones and random noise in genomic mapping.

Experimental noise and noncontiguous clone inserts can pose serious problems in reconstructing genomic maps from hybridization data. We describe an algorithm that easily identifies false positive signals and clones containing chimeric inserts/internal deletions. The algorithm "dechimerizes" clones, splitting them into independent contiguous components and cleaning the initial library into a more consistent data set for further ordering. The effectiveness of the algorithm is demonstrated on both simulated data and the real YAC map of the whole genome of the fission yeast Schizosaccharomyces pombe.

Algorithms

An integrated YAC-overlap and 'cosmid-pocket' map of the human chromosome 21.

We describe here the construction of an ordered clone map of human chromosome 21, based on the identification of ordered sets of YAC clones covering > 90% of the chromosome, and their use to identify groups of cosmid clones (cosmid pockets) localised to subregions defined by the YAC clone map. This is to our knowledge the highest resolution map of one human chromosome to date, localising 530 YAC clones covering both arms of the chromosome, spanning > 36 Mbp, and localising more than 6300 cosmids to 145 intervals on both arms of the chromosome. The YAC contigs have been formed by hybridising a 6.1 equivalents chromosome 21 enriched YAC collection displayed on arrayed nylon membranes to a series of 115 DNA markers and Alu-PCR products from YACs. Forty eight mega-YACs from the previously published CEPH-Genethon map of sequence tagged sites (STS) have also been included in the contig building experiments. A YAC tiling path was then size-measured and confirmed by gel-fingerprinting. A minimal tiling path of 70 YACs were then used as probes against the 7.5 genome equivalents flow sorted chromosome 21 cosmid library in order to identify the lists of cosmids mapping to alternating shared--non-shared intervals between overlapping YACs ('cosmid pockets'). For approximately 1/5 of the minimal tiling path of YACs, locations and non-chimaerism have been confirmed by fluorescence in situ hybridisation (FISH), and approximately 1/5 of all cosmid pocket assignments have independent, confirmatory marker hybridizations in the ICRF cosmid reference library system. We also demonstrate that 'pockets' contain overlapping sets of cosmids (cosmid contigs). In addition to being an important logical intermediate step between the YAC maps published so far and a future map of completely ordered cosmids, this map provides immediately available low-complexity cosmid material for high resolution FISH mapping of chromosomal aberrations on interphase nuclei, and for rapid positional isolation of transcripts in the highly resolved regions of genetic interest.

Chromosome Mapping

Algorithms and software tools for ordering clone libraries: application to the mapping of the genome of Schizosaccharomyces pombe.

A complete set of software tools to aid the physical mapping of a genome has been developed and successfully applied to the genomic mapping of the fission yeast Schizosaccharomyces pombe. Two approaches were used for ordering single-copy hybridisation probes: one was based on the simulated annealing algorithm to order all probes, and another on inferring the minimum-spanning subset of the probes using a heuristic filtering procedure. Both algorithms produced almost identical maps, with minor differences in the order of repetitive probes and those having identical hybridisation patterns. A separate algorithm fitted the clones to the established probe order. Approaches for handling experimental noise and repetitive elements are discussed. In addition to these programs and the database management software, tools for visualizing and editing the data are described. The issues of combining the information from different libraries are addressed. Also, ways of handling multiple-copy probes and non-hybridisation data are discussed.

Algorithms