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Biomedical subjects

S Hazout

Publications and source records attributed to S Hazout.

At least 37 records · Page 2Linked to original sources

Hydrophobic neighboring homology (HNH) dotplot: an approach for assessing structurally similar motifs in proteins.

Structural biology needs sensitive tools to detect homology between proteins of low sequence identity, but with closely related 3-D structures. Using a conventional dotplot method, we therefore introduced 2 concepts to improve the search for similarities between secondary structures of analyzed proteins: 'hydrophobic neighboring homology' (HNH) and 'amino acid degeneracy classes'. The amino acids are grouped into 3 subsets: hydrophobic, hydrophilic and mimetic. A 'Neighboring Similarity Index' (NSI) is calculated for every residue pair and quantifies its neighbor homology. By thresholding the homology matrix and filtering the dotplot, the homologous patterns are extracted. We have evaluated the efficiency and limits of the method using 21 protein pairs extracted from the Protein Data Bank (PDB), or selected from the recent literature. Globally, we again find the homologous structures (alpha-helices and beta-strands) of these pair proteins. The introduction of neighbor residue hydrophobicity in the conventional dotplot improves the alignment of proteins with low sequence identity (< 25%). HNH, written in standard ANSI C with the graphic library X11, under UNIX, is available on request.

Cluster Analysis↗

"Iso-depth contour map" of a molecular surface.

The representation and display of protein surfaces are useful in many areas of molecular modeling, and surface shape study is particularly important in the analysis of protein-ligand interactions. We introduce here the notion of the molecular surface convex hull, allowing the depth of any molecular surface point to be defined. A two-dimensional (2D) map, the iso-depth contour map, and a three-dimensional (3D) representation, the iso-depth lines, allow the topography of a molecular surface to be displayed in terms of knobs (high depth) and holes (low depth).

Computer Graphics↗

A new approach for interpreting the genetic diversity in space: 'Mobile Site Method'. Application to Gm haplotype distribution of twenty-seven Amerindian tribes from North and Central America.

We present a new approach, called 'Mobile Site Method' (MSM), to the construction of 'genetic similarity maps' more efficient than that described in a preceding paper (Hazout et al. 1991). After building a triangular mesh between the geographical sites, the method consists of moving these locations at each iteration to reduce the overall differences between the geographic and genetic distances. The genetic similarity map, i.e. the final distorted map, allows the interpretation of the genetic diversity of a population set. We have applied this method to the study of Gm immunoglobulin allotypes of twenty-seven Amerindian groups from North and Central America. By a local weighted linear regression, we have reconstituted the distorted contour of America. This representation completes the observations of the sites during the map distortion. In this study, we have defined a large geographical factor in the genetic data (84% of the variability explained), related to a linguistic factor.

Central America↗

Immunoglobulin Gm allotypes in apes: comparison with man.

Serum samples from 245 apes (184 Pan troglodytes, five Pan paniscus, 28 Gorilla gorilla, 23 Pongo pygmaeus abelei, and five Pongo pygmaeus pygmaeus) were tested for G1m (1,2,3,17), G2m (23), and G3m (5,6,10,11,13,14,15,16,21,24,28) immunoglobulin allotypes by the classical method of inhibition of hemagglutination. Some phenotypes are species specific while a few are shared by man and African apes.

Animals↗

Searching for geometric molecular shape complementarity using bidimensional surface profiles.

The study presented herein is a bidimensional approach to the complementarity of two molecular surfaces. From two chosen sections we have established a methodology of generating the optimal matching of two shapes. Our approach consists in describing two molecular surface sections by a shape vector (the angular profile), in finding their matching patterns by comparison of the two profiles, and in optimizing the relative locations of the two sections in two-dimensional space, using rotations and translations defined by geometric characteristics. The set of optimal configurations are successively displayed on a screen. Satisfying results have been obtained for the matching of the complex kallikreine A-trypsin pancreatic bovin 2. This efficient method could be used as a preprocessing for a tridimensional shape complementarity approach between two molecular surfaces.

Animals↗

A method for delineating structurally homogeneous regions in protein sequences.

A homogeneous region in a protein sequence is a set of contiguous residues that share common features, concerning physico-chemical, structural and mutational information. This paper presents a method for identifying such homogeneous regions. From a profile describing a given type of biological information along the sequence, the algorithm allows the segmentation of the sequence by optimizing a criterion characterized by two user-defined control parameters: the 'homogenizing degree' of the regions and the 'site neighbourhood' size. We apply the method to the envelope proteins of the human immunodeficiency virus HIV-1, for the identification of homogeneous regions in a hydrophobicity profile and the delineation of variable and conserved regions in a variability profile.

Algorithms↗

[Familial Alzheimer's disease in France: results of a preliminary survey].

This study concerns French families with Alzheimer's disease (13 families, with 37 diseased individuals). The incidence of female patients is higher than that of males. Variance of the age of onset is less important for intra-familial than inter-familial cases. The mean duration of the disease is shorter for early onset forms. One of these families was retained for molecular genetics studies.

Age Factors↗

FORME: an interactive package for protein backbone deformation.

The FORME package presented herein is designed for modeling purposes: It allows interactive deformation of the protein backbone. General formalism on transformations is introduced and the operators of stretching inside an "acceptance area" and stretching with end-block invariance (i.e., governed by a translational moving) are described. A discussion is presented on the choice of strategy to achieve an interactive deformation tool. Perspectives about complex transformations are presented.

Computer Graphics↗

A new approach to the rapid determination of protein side chain conformations.

Two efficient algorithms have been developed which allow amino acid side chain conformations to be optimized rapidly for a given peptide backbone conformation. Both these approaches are based on the assumption that each side chain can be represented by a small number of rotameric states. These states have been obtained by a dynamic cluster analysis of a large data base of known crystallographic structures. Successful applications of these algorithms to the prediction of known protein conformations are presented.

Algorithms↗

MASH: an interactive program for multiple alignment and consensus sequence construction for biological sequences.

This paper presents a method for the multiple alignment of a sequence set. The MASH algorithm uses a non-redundant database of common motifs and an 'alignment priority' criterion that depends on the length and the occurrence frequency of the patterns in the set of sequences. This user-defined criterion allows the determination of the series of the patterns to be aligned. This program is applied to a fragment of envelope gene env gp120 for 20 isolates of the immunodeficiency virus. The multiplicity of alignments obtained by modifying the criterion parameters reveals different aspects of similarity between the sequences.

Algorithms↗

'Size leap' algorithm: an efficient extraction of the longest common motifs from a molecular sequence set. Application to the DNA sequence reconstruction.

We propose a new method, called 'size leap' algorithm, of search for motifs of maximum size and common to two fragments at least. It allows the creation of a reduced database of motifs from a set of sequences whose size obeys the series of Fibonacci numbers. The convenience lies in the efficiency of the motif extraction. It can be applied in the establishment of overlap regions for DNA sequence reconstruction and multiple alignment of biological sequences. The method of complete DNA sequence reconstruction by extraction of the longest motifs ('anchor motifs') is presented as an application of the size leap algorithm. The details of a reconstruction from three sequenced fragments are given as an example.

Algorithms↗

Genetic similarity maps and immunoglobulin allotypes of eleven populations from the Pyrenees (France).

The genetic heterogeneity of eleven populations from the Pyrenees (France) based on the polymorphism of the immunoglobulin allotypes is studied by means of a 'genetic similarity map'. The method described here, called 'Mobile Node Method', allows the deformation of a square grid, in which the studied region is represented, by moving the nodes at each step in order to reduce the difference between the geographic and genetic distances. This tool allows the overall quantification of the genetic heterogeneity of a population set and possibly the study of its dynamics. Other maps constructed to complete the interpretation are 'map of moving vectors', 'iso-displacement curves' and 'site displacements'. This study identified an overall genetic homogeneity among the Pyrenean populations and several local genetic heterogeneities in different regions.

France↗

The p49/TaqI Y-specific DNA haplotypes in Australian aborigines.

The TaqI/p49 Y-specific RFLPs were studied in 59 Australian aborigines. A new haplotype was found (not present in Caucasians and Africans, number XXV). In the revised genealogy of haplotypes, Australian haplotypes appear to occupy an intermediate position between African Pygmies and Papua haplotypic repartitions, while the most common Australian haplotypes (haplotype III, 25% of the subjects) is apparently derived from them.

Australia↗

The p49/TaqI Y-specific polymorphisms in three groups of Indians.

The TaqI/p49 Y-specific RFLPs were studied in 98 Indians coming from 3 locations in the country. A new allele (G0) and five new haplotypes (XX-XXIV) were found, not present in Caucasians and in Africans. In the genealogy of haplotypes, the new Indian haplotypes appear grouped together, and all Indian haplotypes occupy an intermediate position between Caucasian and African haplotypes.

Alleles↗

Y chromosome DNA polymorphisms in two African populations.

Y chromosome-specific DNA polymorphisms were detected using probe p49f after restriction with TaqI enzyme on samples coming from two African populations: Bantus and Pygmies. All the main TaqI alleles at five Y loci already found in Caucasians are also found in these two populations; 12 of the 16 Caucasian haplotypes were found in these two African populations, and two new haplotypes are Pygmy specific. A proposed phylogeny of the various haplotypes that was derived by using the parsimony criterion established that haplotypes XIII and XVIII, respectively the most frequent one and only one present in Pygmies, are probably ancestral.

Alleles↗

Modelling the 1985 influenza epidemic in France.

The Rvachev-Baroyan-Longini model is a space-time predictive model of the spread of influenza epidemics. It has been applied to 128 cities of the USSR, and more recently, to forecasting the spread of the pandemic of 1968-1969 throughout 52 large cities. It is a deterministic, mass-action, space and time continuous model. The model has been applied to the simulation of the influenza epidemic of 1984-1985 in the 22 French Metropolitan districts and results are presented. Estimates of the parameters of the model were made using the French Communicable Diseases Network data. These parameters are the contact rate, a, (estimate = 0.55) which is the number of people with whom an infectious individual will make contact daily sufficient to pass infection and the infectious period, 1/b, estimated as 2.49 days. The mean annual railroad passenger traffic from district i to district j varies from 0 to 1,991,000 persons depending on the districts. The computer spread of the epidemic is presented on weekly maps. Results are also presented on district charts, giving the size of district epidemics and the time of peak of the epidemic. The precision of the computer fittings was judged satisfactory by the calculated size of peak differing from the real one by less than 100 per cent, in 17 out of 18 districts, and by the calculated time of peak differing from the observed by less than two weeks in 14 out of 18 districts. Although precision could be improved with more detailed information about passenger traffic, the French use of the model has been satisfactory.

Computer Simulation↗