Summary of complementation groups of UV-sensitive CHO cell mutants isolated by large-scale screening

David Busch; Carol Greiner; Kathy Lewis; Ruth Ford; Gerald Adair; Larry Thompson

doi:10.1093/mutage/4.5.349

Genetic Analysis of Salt-Tolerant Mutants in Arabidopsis thaliana

Genetics ◽

10.1093/genetics/154.1.421 ◽

2000 ◽

Vol 154 (1) ◽

pp. 421-436 ◽

Cited By ~ 1

Author(s):

Víctor Quesada ◽

María Rosa Ponce ◽

José Luis Micol

Keyword(s):

Arabidopsis Thaliana ◽

Large Scale ◽

Crop Productivity ◽

Protein Product ◽

Incomplete Penetrance ◽

Complementation Groups ◽

Mutant Lines ◽

Agricultural Areas ◽

Ionic Effects ◽

Large Scale Screening

Abstract Stress caused by the increased salinity of irrigated fields impairs plant growth and is one of the major constraints that limits crop productivity in many important agricultural areas. As a contribution to solving such agronomic problems, we have carried out a large-scale screening for Arabidopsis thaliana mutants induced on different genetic backgrounds by EMS treatment, fast neutron bombardment, or T-DNA insertions. From the 675,500 seeds we screened, 17 mutant lines were isolated, all but one of which yielded 25–70% germination levels on 250 mm NaCl medium, a condition in which their ancestor ecotypes are unable to germinate. Monogenic recessive inheritance of NaCl-tolerant germination was displayed with incomplete penetrance by all the selected mutants, which fell into five complementation groups. These were named SALOBREÑO (SAÑ) and mapped relative to polymorphic microsatellites, the map positions of three of them suggesting that they are novel genes. Strains carrying mutations in the SAÑ1-SAÑ4 genes display similar responses to both ionic effects and osmotic pressure, their germination being NaCl and mannitol tolerant but KCl and Na2SO4 sensitive. In addition, NaCl-, KCl-, and mannitol-tolerant as well as abscisic-acid-insensitive germination was displayed by sañ5, whose genetic and molecular characterization indicates that it carries an extremely hypomorphic or null allele of the ABI4 gene, its deduced protein product lacking the APETALA2 DNA binding domain.

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A Mutational Analysis of Leaf Morphogenesis in Arabidopsis thaliana

Genetics ◽

10.1093/genetics/152.2.729 ◽

1999 ◽

Vol 152 (2) ◽

pp. 729-742 ◽

Cited By ~ 3

Author(s):

Genoveva Berná ◽

Pedro Robles ◽

José Luis Micol

Keyword(s):

Arabidopsis Thaliana ◽

Large Scale ◽

Mutational Analysis ◽

Leaf Ontogeny ◽

Leaf Morphogenesis ◽

Complete Penetrance ◽

Complementation Groups ◽

Mutant Phenotypes ◽

Leaf Mutants ◽

Large Scale Screening

Abstract As a contribution to a better understanding of the developmental processes that are specific to plants, we have begun a genetic analysis of leaf ontogeny in the model system Arabidopsis thaliana by performing a large-scale screening for mutants with abnormal leaves. After screening 46,159 M2 individuals, arising from 5770 M1 parental seeds exposed to EMS, we isolated 1926 M2 putative leaf mutants, 853 of which yielded viable M3 inbred progeny. Mutant phenotypes were transmitted with complete penetrance and small variations in expressivity in 255 lines. Most of them were inherited as recessive monogenic traits, belonging to 94 complementation groups, which suggests that we did not reach saturation of the genome. We discuss the nature of the processes presumably perturbed in the phenotypic classes defined among our mutants.

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Training Aides to Screen Children for Speech and Language Problems

Language Speech and Hearing Services in Schools ◽

10.1044/0161-1461.0704.236 ◽

1976 ◽

Vol 7 (4) ◽

pp. 236-241 ◽

Cited By ~ 5

Author(s):

Marisue Pickering ◽

William R. Dopheide

Keyword(s):

Rural Areas ◽

Large Scale ◽

School Personnel ◽

School Age Children ◽

Speech And Language ◽

Elementary School Age ◽

Evaluation Procedures ◽

Language Problems ◽

Competency Based ◽

Large Scale Screening

This report deals with an effort to begin the process of effectively identifying children in rural areas with speech and language problems using existing school personnel. A two-day competency-based workshop for the purpose of training aides to conduct a large-scale screening of speech and language problems in elementary-school-age children is described. Training strategies, implementation, and evaluation procedures are discussed.

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Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190122151634 ◽

2019 ◽

Vol 19 (1) ◽

pp. 4-16 ◽

Cited By ~ 6

Author(s):

Qihui Wu ◽

Hanzhong Ke ◽

Dongli Li ◽

Qi Wang ◽

Jiansong Fang ◽

...

Keyword(s):

Machine Learning ◽

Drug Discovery ◽

Large Scale ◽

Recent Progress ◽

High Specificity ◽

Learning Approaches ◽

Anticancer Peptides ◽

The Past ◽

Traditional Approaches ◽

Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

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Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening

Diagnostics ◽

10.3390/diagnostics11050869 ◽

2021 ◽

Vol 11 (5) ◽

pp. 869

Author(s):

Amedeo De Nicolò ◽

Valeria Avataneo ◽

Jessica Cusato ◽

Alice Palermiti ◽

Jacopo Mula ◽

...

Keyword(s):

Early Diagnosis ◽

Real Time Pcr ◽

Large Scale ◽

High Sensitivity ◽

Analytical Validation ◽

Pcr Assay ◽

Serological Tests ◽

Flow Test ◽

Lateral Flow Test ◽

Large Scale Screening

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.

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Genetic and Molecular Analysis of Region 88E9;88F2 in Drosophila melanogaster, Including the ear Gene Related to Human Factors Involved in Lineage-Specific Leukemias

Genetics ◽

10.1093/genetics/160.3.1051 ◽

2002 ◽

Vol 160 (3) ◽

pp. 1051-1065

Author(s):

Claudia B Zraly ◽

Yun Feng ◽

Andrew K Dingwall

Keyword(s):

Large Scale ◽

Drosophila Genome ◽

Embryonic Cells ◽

Ems Mutagenesis ◽

Recessive Lethal ◽

Protein Levels ◽

Late Embryogenesis ◽

Complementation Groups ◽

Mammalian Genes ◽

Map Location

Abstract We identified and characterized the Drosophila gene ear (ENL/AF9-related), which is closely related to mammalian genes that have been implicated in the onset of acute lymphoblastic and myelogenous leukemias when their products are fused as chimeras with those of human HRX, a homolog of Drosophila trithorax. The ear gene product is present in all early embryonic cells, but becomes restricted to specific tissues in late embryogenesis. We mapped the ear gene to cytological region 88E11-13, near easter, and showed that it is deleted by Df(3R)ea5022rx1, a small, cytologically invisible deletion. Annotation of the completed Drosophila genome sequence suggests that this region might contain as many as 26 genes, most of which, including ear, are not represented by mutant alleles. We carried out a large-scale noncom-plementation screen using Df(3R)ea5022rx1 and chemical (EMS) mutagenesis from which we identified sevenc novel multi-allele recessive lethal complementation groups in this region. An overlapping deficiency, Df(3R)Po4, allowed us to map several of these groups to either the proximal or the distal regions of Df(3R)ea5022rx1. One of these complementation groups likely corresponds to the ear gene as judged by map location, terminal phenotype, and reduction of EAR protein levels.

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BonMOLière: Small-Sized Libraries of Readily Purchasable Compounds, Optimized to Produce Genuine Hits in Biological Screens across the Protein Space

International Journal of Molecular Sciences ◽

10.3390/ijms22157773 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7773

Author(s):

Neann Mathai ◽

Conrad Stork ◽

Johannes Kirchmair

Keyword(s):

Large Scale ◽

Computational Approach ◽

Large Sets ◽

Compound Libraries ◽

Wide Range ◽

Protein Space ◽

High Chance ◽

Large Scale Screening ◽

Early Drug ◽

Selection Of

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).

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Large-scale screening of natural genetic resource in the hydrocarbon-producing microalga Botrycoccus braunii identified novel fast-growing strains

Scientific Reports ◽

10.1038/s41598-021-86760-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Koji Kawamura ◽

Suzune Nishikawa ◽

Kotaro Hirano ◽

Ardianor Ardianor ◽

Rudy Agung Nugroho ◽

...

Keyword(s):

Large Scale ◽

Biomass Productivity ◽

Botryococcus Braunii ◽

Algal Biofuel ◽

Fast Growing ◽

Wild Strains ◽

Glass Tubes ◽

The Tropics ◽

Large Scale Screening ◽

Hydrocarbon Productivity

AbstractAlgal biofuel research aims to make a renewable, carbon–neutral biofuel by using oil-producing microalgae. The freshwater microalga Botryococcus braunii has received much attention due to its ability to accumulate large amounts of petroleum-like hydrocarbons but suffers from slow growth. We performed a large-scale screening of fast-growing strains with 180 strains isolated from 22 ponds located in a wide geographic range from the tropics to cool-temperate. A fast-growing strain, Showa, which recorded the highest productivities of algal hydrocarbons to date, was used as a benchmark. The initial screening was performed by monitoring optical densities in glass tubes and identified 9 wild strains with faster or equivalent growth rates to Showa. The biomass-based assessments showed that biomass and hydrocarbon productivities of these strains were 12–37% and 11–88% higher than that of Showa, respectively. One strain, OIT-678 established a new record of the fastest growth rate in the race B strains with a doubling time of 1.2 days. The OIT-678 had 36% higher biomass productivity, 34% higher hydrocarbon productivity, and 20% higher biomass density than Showa at the same cultivation conditions, suggesting the potential of the new strain to break the record for the highest productivities of hydrocarbons.

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Identification of Six Loci in Which Mutations Partially Restore Peroxisome Biogenesis and/or Alleviate the Metabolic Defect of pex2 Mutants in Podospora

Genetics ◽

10.1093/genetics/161.3.1089 ◽

2002 ◽

Vol 161 (3) ◽

pp. 1089-1099

Author(s):

Gwenaël Ruprich-Robert ◽

Véronique Berteaux-Lecellier ◽

Denise Zickler ◽

Arlette Panvier-Adoutte ◽

Marguerite Picard

Keyword(s):

Sole Carbon Source ◽

Large Scale ◽

Podospora Anserina ◽

Developmental Defect ◽

Dominant Allele ◽

Peroxisome Biogenesis ◽

Metabolic Defects ◽

Metabolic Defect ◽

Mutant Strains ◽

Large Scale Screening

Abstract Peroxins (PEX) are proteins required for peroxisome biogenesis. Mutations in PEX genes cause lethal diseases in humans, metabolic defects in yeasts, and developmental disfunctions in plants and filamentous fungi. Here we describe the first large-scale screening for suppressors of a pex mutation. In Podospora anserina, pex2 mutants exhibit a metabolic defect [inability to grow on medium containing oleic acid (OA medium) as sole carbon source] and a developmental defect (inability to differentiate asci in homozygous crosses). Sixty-three mutations able to restore growth of pex2 mutants on OA medium have been analyzed. They fall in six loci (suo1 to suo6) and act as dominant, allele-nonspecific suppressors. Most suo mutations have pleiotropic effects in a pex2+ background: formation of unripe ascospores (all loci except suo5 and suo6), impaired growth on OA medium (all loci except suo4 and suo6), or sexual defects (suo4). Using immunofluorescence and GFP staining, we show that peroxisome biogenesis is partially restored along with a low level of ascus differentiation in pex2 mutant strains carrying either the suo5 or the suo6 mutations. The data are discussed with respect to β-oxidation of fatty acids, peroxisome biogenesis, and cell differentiation.

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