Biomedical subjects

Maria Samsonova

Publications and source records attributed to Maria Samsonova.

8 recordsLinked to original sources

PubMed2005

A high-throughput method for quantifying gene expression data from early Drosophila embryos.

We describe an automated high-throughput method to measure protein levels in single nuclei in blastoderm embryos of Drosophila melanogaster by means of immunofluorescence. The method consists of a chain of specific algorithms assembled into an image processing pipeline. This pipeline transforms a confocal scan of an embryo stained with fluorescently tagged antibodies into a text file. This text file contains a numerical identifier for each nucleus, the coordinates of its centroid, and the average concentrations of three proteins in that nucleus. The central algorithmic component of the method is the automatic identification of nuclei by edge detection with the use of watersheds as an error-correction step. This method provides high-throughput quantification at cellular resolution.

Algorithms↗

PubMed2005

Removal of background signal from in situ data on the expression of segmentation genes in Drosophila.

Here we present a method for the removal of nonspecific background signal from fluorescently localized expression patterns of Drosophila segmentation genes. Our algorithm for removal of background signal brings the data to a common standard form with zero background and removes systematic error in gene expression levels caused by the presence of background. The method is based on the discovery, reported here, that background is well fit by a very broad two-dimensional paraboloid. The paraboloid is determined from the area of the embryo in which a given gene is not expressed and the whole pattern is then normalized by this paraboloid to remove background from the entire embryo. The software implementing this algorithm is available from the authors.

Animals↗

PubMed2004

Dynamic control of positional information in the early Drosophila embryo.

Morphogen gradients contribute to pattern formation by determining positional information in morphogenetic fields. Interpretation of positional information is thought to rely on direct, concentration-threshold-dependent mechanisms for establishing multiple differential domains of target gene expression. In Drosophila, maternal gradients establish the initial position of boundaries for zygotic gap gene expression, which in turn convey positional information to pair-rule and segment-polarity genes, the latter forming a segmental pre-pattern by the onset of gastrulation. Here we report, on the basis of quantitative gene expression data, substantial anterior shifts in the position of gap domains after their initial establishment. Using a data-driven mathematical modelling approach, we show that these shifts are based on a regulatory mechanism that relies on asymmetric gap-gap cross-repression and does not require the diffusion of gap proteins. Our analysis implies that the threshold-dependent interpretation of maternal morphogen concentration is not sufficient to determine shifting gap domain boundary positions, and suggests that establishing and interpreting positional information are not independent processes in the Drosophila blastoderm.

Animals↗

PubMed2004

A database for management of gene expression data in situ.

MOTIVATION: To create a spatiotemporal atlas of Drosophila segmentation gene expression at cellular resolution. RESULTS: The expression of segmentation genes plays a crucial role in the establishment of the Drosophila body plan. Using the IBM DB2 Relational Database Management System we have designed and implemented the FlyEx database. FlyEx contains 2832 images of 14 segmentation gene expression patterns obtained from 954 embryos and 2,073,662 quantitative data records. The averaged data is available for most of segmentation genes at eight time points. FlyEx supports operations on images of gene expression patterns. The database can be used to examine the quality of data, analyze the dynamics of formation of segmentation gene expression domains, as well as estimate the variability of gene expression patterns. We also provide the capability to download data of interest. AVAILABILITY: http://urchin.spbcas.ru/flyex, http://flyex.ams.sunysb.edu/flyex

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PubMed2004

Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster.

Genetic studies have revealed that segment determination in Drosophila melanogaster is based on hierarchical regulatory interactions among maternal coordinate and zygotic segmentation genes. The gap gene system constitutes the most upstream zygotic layer of this regulatory hierarchy, responsible for the initial interpretation of positional information encoded by maternal gradients. We present a detailed analysis of regulatory interactions involved in gap gene regulation based on gap gene circuits, which are mathematical gene network models used to infer regulatory interactions from quantitative gene expression data. Our models reproduce gap gene expression at high accuracy and temporal resolution. Regulatory interactions found in gap gene circuits provide consistent and sufficient mechanisms for gap gene expression, which largely agree with mechanisms previously inferred from qualitative studies of mutant gene expression patterns. Our models predict activation of Kr by Cad and clarify several other regulatory interactions. Our analysis suggests a central role for repressive feedback loops between complementary gap genes. We observe that repressive interactions among overlapping gap genes show anteroposterior asymmetry with posterior dominance. Finally, our models suggest a correlation between timing of gap domain boundary formation and regulatory contributions from the terminal maternal system.

Animals↗

PubMed2002

Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers.

Ionizing radiation is a potent lung carcinogen, but the precise molecular damage associated with it is still unknown. In this study we investigated cancer-related molecular abnormalities including K-ras (codon 12) mutation, p16(INK4A) promoter hypermethylation and microsatellite alterations at seven chromosomal regions in successive biopsies obtained from former Chernobyl cleanup workers in comparison with smokers and nonsmokers who have never had radiation exposure. Our results indicate that prolonged persistence of inhaled radioactive particles is associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24 (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up workers. The prevalence of 3p14.2 allelic loss was associated with decreased expression of the FHIT mRNA in their bronchial epithelium in comparison with control group of smokers. During several years of our monitoring samples of epithelium were collected from the same area of bronchial tree. In epithelium exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of molecular abnormalities was significantly higher in dysplasia and in morphologically normal foci progressed later to dysplasia than in these samples which never showed evidence of such progression. Our findings indicate that extensive cancer-related molecular abnormalities sequentially occur in radiation damaged bronchial epithelium of former Chernobyl clean-up workers.

Acid Anhydride Hydrolases↗

PubMed2002

Temporal classification of Drosophila segmentation gene expression patterns by the multi-valued neural recognition method.

In order to reconstruct the establishment of the body pattern over time in Drosophila embryos, we have developed automated methods for detecting the age of an embryo on the basis of knowledge about its gene expression patterns. In this paper we perform temporal classification of confocal images of expression patterns of genes controlling segmentation by means of a neural network based on multi-valued neurons (MVN). MVN are artificial neural processing elements with complex-valued weights and high functionality, which proved to be efficient for solving the image recognition problems. The results obtained by this method confirm its efficiency for image recognition and indicate that the method can detect characteristic features of expression patterns which mark their development over time.

Animals↗

PubMed2002

A method for two-dimensional registration and construction of the two-dimensional atlas of gene expression patterns in situ.

We apply the fast redundant dyadic wavelet transform to the spatial registration of two-dimensional gene expression patterns of 736 Drosophila melanogaster embryos. This method is superior to the Fourier transform or windowed Fourier transform because of its ability to reduce noise and is of high resolution. In registration of the dataset we use two cost functions based on computing the Euclidean or Mahalanobis distance. The algorithm shows a high level of accuracy. For early temporal classes the cost function based on Mahalanobis distance gives better results. We have reported a method for construction of an integrated dataset elsewhere. In this paper the method is extended to the two-dimensional case. The procedure for data assembly provides for the preservation of some aspects of the nuclear structure of a two-dimensional gene expression pattern. It is based on creating an averaged model that reproduces the spatial distribution of nuclei over the embryo image. The average concentrations of each protein in each averaged nucleus are computed from the series of embryos of the same age.

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