scholarly journals Large Scale Identification of Genes Involved in Cell Surface Biosynthesis and Architecture in Saccharomyces cerevisiae

Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 435-450 ◽  
Author(s):  
Marc Lussier ◽  
Ann-Marie White ◽  
Jane Sheraton ◽  
Tiziano di Paolo ◽  
Julie Treadwell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Large Scale ◽  
Cell Function ◽  
Eukaryotic Cell ◽  
Yeast Genome ◽  
Calcofluor White ◽  
Genome Database ◽  
Cellular Processes ◽  
Genome Wide ◽  
Mutant Phenotypes

The sequenced yeast genome offers a unique resource for the analysis of eukaryotic cell function and enables genome-wide screens for genes involved in cellular processes. We have identified genes involved in cell surface assembly by screening transposon-mutagenized cells for altered sensitivity to calcofluor white, followed by supplementary screens to further characterize mutant phenotypes. The mutated genes were directly retrieved from genomic DNA and then matched uniquely to a gene in the yeast genome database. Eighty-two genes with apparent perturbation of the cell surface were identified, with mutations in 65 of them displaying at least one further cell surface phenotype in addition to their modified sensitivity to calcofluor. Fifty of these genes were previously known, 17 encoded proteins whose function could be anticipated through sequence homology or previously recognized phenotypes and 15 genes had no previously known phenotype.

scholarly journals Deep Annotation of Protein Function across Diverse Bacteria from Mutant Phenotypes

2016 ◽  
Author(s):  
Morgan N. Price ◽  
Kelly M. Wetmore ◽  
R. Jordan Waters ◽  
Mark Callaghan ◽  
Jayashree Ray ◽  
...  
Keyword(s):  
Protein Function ◽  
Large Scale ◽  
Hypothetical Proteins ◽  
Data Set ◽  
Protein Coding ◽  
Bacterial Proteins ◽  
Genome Wide ◽  
Protein Functions ◽  
Mutant Phenotypes ◽  
Related Proteins

SummaryThe function of nearly half of all protein-coding genes identified in bacterial genomes remains unknown. To systematically explore the functions of these proteins, we generated saturated transposon mutant libraries from 25 diverse bacteria and we assayed mutant phenotypes across hundreds of distinct conditions. From 3,903 genome-wide mutant fitness assays, we obtained 14.9 million gene phenotype measurements and we identified a mutant phenotype for 8,487 proteins with previously unknown functions. The majority of these hypothetical proteins (57%) had phenotypes that were either specific to a few conditions or were similar to that of another gene, thus enabling us to make informed predictions of protein function. For 1,914 of these hypothetical proteins, the functional associations are conserved across related proteins from different bacteria, which confirms that these associations are genuine. This comprehensive catalogue of experimentally-annotated protein functions also enables the targeted exploration of specific biological processes. For example, sensitivity to a DNA-damaging agent revealed 28 known families of DNA repair proteins and 11 putative novel families. Across all sequenced bacteria, 14% of proteins that lack detailed annotations have an ortholog with a functional association in our data set. Our study demonstrates the utility and scalability of high-throughput genetics for large-scale annotation of bacterial proteins and provides a vast compendium of experimentally-determined protein functions across diverse bacteria.

scholarly journals Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome

2021 ◽  
Vol 49 (3) ◽  
pp. 1497-1516
Author(s):  
Wilfried M Guiblet ◽  
Marzia A Cremona ◽  
Robert S Harris ◽  
Di Chen ◽  
Kristin A Eckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Nucleotide Substitution ◽  
Genetic Diseases ◽  
Nucleotide Polymorphisms ◽  
Dna Structures ◽  
Cellular Processes ◽  
Genome Wide ◽  
Dna Types ◽  
Flanking Regions

Abstract Approximately 13% of the human genome can fold into non-canonical (non-B) DNA structures (e.g. G-quadruplexes, Z-DNA, etc.), which have been implicated in vital cellular processes. Non-B DNA also hinders replication, increasing errors and facilitating mutagenesis, yet its contribution to genome-wide variation in mutation rates remains unexplored. Here, we conducted a comprehensive analysis of nucleotide substitution frequencies at non-B DNA loci within noncoding, non-repetitive genome regions, their ±2 kb flanking regions, and 1-Megabase windows, using human-orangutan divergence and human single-nucleotide polymorphisms. Functional data analysis at single-base resolution demonstrated that substitution frequencies are usually elevated at non-B DNA, with patterns specific to each non-B DNA type. Mirror, direct and inverted repeats have higher substitution frequencies in spacers than in repeat arms, whereas G-quadruplexes, particularly stable ones, have higher substitution frequencies in loops than in stems. Several non-B DNA types also affect substitution frequencies in their flanking regions. Finally, non-B DNA explains more variation than any other predictor in multiple regression models for diversity or divergence at 1-Megabase scale. Thus, non-B DNA substantially contributes to variation in substitution frequencies at small and large scales. Our results highlight the role of non-B DNA in germline mutagenesis with implications to evolution and genetic diseases.

scholarly journals KRGDB: the large-scale variant database of 1722 Koreans based on whole genome sequencing

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Kwang Su Jung ◽  
Kyung-Won Hong ◽  
Hyun Youn Jo ◽  
Jongpill Choi ◽  
Hyo-Jeong Ban ◽  
...  
Keyword(s):  
Large Scale ◽  
Genome Wide Association Study ◽  
Regulatory Elements ◽  
Genome Database ◽  
Genome Wide ◽  
Variant Frequency ◽  
Different Origins ◽  
Java Server Page ◽  
First Time ◽  
Reference Genome Database

Abstract Since 2012, the Center for Genome Science of the Korea National Institute of Health (KNIH) has been sequencing complete genomes of 1722 Korean individuals. As a result, more than 32 million variant sites have been identified, and a large proportion of the variant sites have been detected for the first time. In this article, we describe the Korean Reference Genome Database (KRGDB) and its genome browser. The current version of our database contains both single nucleotide and short insertion/deletion variants. The DNA samples were obtained from four different origins and sequenced in different sequencing depths (10× coverage of 63 individuals, 20× coverage of 194 individuals, combined 10× and 20× coverage of 135 individuals, 30× coverage of 230 individuals and 30× coverage of 1100 individuals). The major features of the KRGDB are that it contains information on the Korean genomic variant frequency, frequency difference between the Korean and other populations and the variant functional annotation (such as regulatory elements in ENCODE regions and coding variant functions) of the variant sites. Additionally, we performed the genome-wide association study (GWAS) between Korean genome variant sites for the 30×230 individuals and three major common diseases (diabetes, hypertension and metabolic syndrome). The association results are displayed on our browser. The KRGDB uses the MySQL database and Apache-Tomcat web server adopted with Java Server Page (JSP) and is freely available at http://coda.nih.go.kr/coda/KRGDB/index.jsp. Availability: http://coda.nih.go.kr/coda/KRGDB/index.jsp

scholarly journals Eukaryo: An AR and VR Application for Cell Biology

2016 ◽  
Vol 16 (1) ◽  
pp. 7-14
Author(s):  
Douglas Yuen ◽  
Markus Santoso ◽  
Stephen Cartwright ◽  
Christian Jacob
Keyword(s):  
Cell Biology ◽  
High Performance ◽  
Large Scale ◽  
Eukaryotic Cell ◽  
Cellular Functions ◽  
3 Dimensional ◽  
Cellular Processes ◽  
Head Mounted Displays ◽  
Biological Environment ◽  
Immersive Visualization

Eukaryo is a simulated bio-molecular world that allows users to explore the complex environment within a biological cell. Eukaryo was developed using Unity, leveraging the capabilities and high performance of a commercial game engine. Through the use of MiddleVR, our tool can support a wide variety of interaction platforms including 3D virtual reality (VR) environments, such as head-mounted displays, augmented reality (AR) headsets, and large scale immersive visualization facilities. Our interactive, 3-dimensional model demonstrates key functional elements of a generic eukaryotic cell. Users are able to use multiple modes to explore the cell, its structural elements, its organelles, and some key metabolic processes. In contrast to textbook diagrams and even videos, Eukaryo immerses users directly in the biological environment, giving a more effective demonstration of how cellular processes work, how compartmentalization affects cellular functions, and how the machineries of life operate.

scholarly journals Large-Scale Gene Expression Data Analysis: A New Challenge to Computational Biologists

1999 ◽  
Vol 9 (8) ◽  
pp. 681-688 ◽  
Author(s):  
Michael Q. Zhang
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Large Scale ◽  
Yeast Genome ◽  
Expression Data ◽  
Dna Arrays ◽  
Gene Expression Data Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

The use of high-density DNA arrays to monitor gene expression at a genome-wide scale constitutes a fundamental advance in biology. In particular, the expression pattern of all genes in Saccharomyces cerevisiae can be interrogated using microarray analysis where cDNAs are hybridized to an array of each of the ∼6000 genes in the yeast genome. In this survey I review three recent experiments related to transcriptional regulation and discuss the great challenge for computational biologists trying to extract functional information from such large-scale gene expression data.

scholarly journals Quantitative Genome-Wide Analysis of Yeast Deletion Strain Sensitivities to Oxidative and Chemical Stress

2004 ◽  
Vol 5 (3) ◽  
pp. 216-224 ◽  
Author(s):  
Chandra L. Tucker ◽  
Stanley Fields
Keyword(s):  
Hydrogen Peroxide ◽  
Large Scale ◽  
Chemical Resistance ◽  
Lethal Effect ◽  
Sublethal Dose ◽  
Synthetic Lethal ◽  
Cellular Processes ◽  
Molecular Events ◽  
Genome Wide ◽  
A Cell

Understanding the actions of drugs and toxins in a cell is of critical importance to medicine, yet many of the molecular events involved in chemical resistance are relatively uncharacterized. In order to identify the cellular processes and pathways targeted by chemicals, we took advantage of the haploidSaccharomyces cerevisiaedeletion strains (Winzeleret al.,1999). Although ~4800 of the strains are viable, the loss of a gene in a pathway affected by a drug can lead to a synthetic lethal effect in which the combination of a deletion and a normally sublethal dose of a chemical results in loss of viability. WE carried out genome-wide screens to determine quantitative sensitivities of the deletion set to four chemicals: hydrogen peroxide, menadione, ibuprofen and mefloquine. Hydrogen peroxide and menadione induce oxidative stress in the cell, whereas ibuprofen and mefloquine are toxic to yeast by unknown mechanisms. Here we report the sensitivities of 659 deletion strains that are sensitive to one or more of these four compounds, including 163 multichemicalsensitive strains, 394 strains specific to hydrogen peroxide and/or menadione, 47 specific to ibuprofen and 55 specific to mefloquine.We correlate these results with data from other large-scale studies to yield novel insights into cellular function.

Some Aspects of the Polyhexamethyleneguanidine Salts Effect on Cell Cultures

2014 ◽  
Vol 1 (1) ◽  
pp. 62-67 ◽  
Author(s):  
M. Mandygra ◽  
A. Lysytsia
Keyword(s):  
Proliferative Activity ◽  
Cell Monolayer ◽  
Eukaryotic Cell ◽  
Culture Methods ◽  
Cellular Processes ◽  
Negative Effect ◽  
Membrane Bound ◽  
Membrane Bound Enzymes ◽  
Anion Type ◽  
Cell Culture Methods

Aim. To investigate the effect of polyhexamethyleneguanidine (PHMG) to eukaryotic cell culture. Methods. The passaged bovine tracheal cells culture (TCC) and primary culture of chicken embryo fi broblasts (FCE) were used in the experiments. TCC and FCE monolayers were treated with aqueous solutions of PHMG chloride or succinate. The method of PHMG polycation adsorption to the cells’ plasma membrane together with microscopy were applied. Results. The dependence of PHMG effect on the eukaryotic cells on the agent concentration, duration of exposure and the anion type has been fi xed. The PHMG concentration of 10 –5 per cent (0.1 μg/ml) never causes degradation of the previously formed cell monolayer, while the higher concentrations damage it. The conditions of the PHMG chloride and succinate’s negative effect on cell proliferation and inhibition of monolayer formation were determined. The hypothesis that under certain conditions PHMG stimulates the proliferative activity of the cells has been confi rmed. Stimulation may be associated with non-specifi c stress adaptation of cells. In this case, it is due to modifi cations of the cell membrane after PHMG adsorption to it. Conclusions. PHMG polycation binds with the membrane’s phosphoglycerides fi rmly and irreversibly. A portion of the lipids are removed from participation in the normal cellular processes at that. At the same time, the synthesis of new lipids and membrane-bound enzymes is probably accelerated. The phospholip ids’ neogenesis acceleration can stimulate mitosis under certain conditions. The obtained results can be used in the biotechnologies.

Sign in / Sign up

Export Citation Format

Share Document