The Chloroplast Function Database: a large-scale collection of ArabidopsisDs/Spm- or T-DNA-tagged homozygous lines for nuclear-encoded chloroplast proteins, and their systematic phenotype analysis

ABSTRACTThe use of comparative genomics for the study of different microbiological species has increased substantially as sequence technologies become more affordable. However, efforts to fully link a genotype to its phenotype remain limited to the development of one mutant at a time. In this study, we provided a high-throughput alternative to this limiting step by coupling comparative genomics to the use of phenotype arrays for five sequencedShewanellastrains. Positive phenotypes were obtained for 441 nutrients (C, N, P, and S sources), with N-based compounds being the most utilized for all strains. Many genes and pathways predicted by genome analyses were confirmed with the comparative phenotype assay, and three degradation pathways believed to be missing inShewanellawere confirmed as missing. A number of previously unknown gene products were predicted to be parts of pathways or to have a function, expanding the number of gene targets for future genetic analyses. Ecologically, the comparative high-throughput phenotype analysis provided insights into niche specialization among the five different strains. For example,Shewanella amazonensisstrain SB2B, isolated from the Amazon River delta, was capable of utilizing 60 C compounds, whereasShewanellasp. strain W3-18-1, isolated from deep marine sediment, utilized only 25 of them. In spite of the large number of nutrient sources yielding positive results, our study indicated that except for the N sources, they were not sufficiently informative to predict growth phenotypes from increasing evolutionary distances. Our results indicate the importance of phenotypic evaluation for confirming genome predictions. This strategy will accelerate the functional discovery of genes and provide an ecological framework for microbial genome sequencing projects.

Download Full-text

Approximate conditional phenotype analysis based on genome wide association summary statistics

Scientific Reports ◽

10.1038/s41598-021-82000-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Peitao Wu ◽

Biqi Wang ◽

Steven A. Lubitz ◽

Emelia J. Benjamin ◽

James B. Meigs ◽

...

Keyword(s):

Large Scale ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Summary Statistics ◽

Phenotypic Data ◽

Individual Level ◽

Genome Wide ◽

Level Data ◽

A Genome ◽

Phenotype Analysis

AbstractBecause single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.

Download Full-text

Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions.

Genetics ◽

10.1093/genetics/132.4.975 ◽

1992 ◽

Vol 132 (4) ◽

pp. 975-985 ◽

Cited By ~ 32

Author(s):

R A Reenan ◽

R D Kolodner

Keyword(s):

Saccharomyces Cerevisiae ◽

Type Strain ◽

Large Scale ◽

Wild Type Strain ◽

Spontaneous Mutation ◽

Single Copy ◽

Wild Type ◽

Dapi Staining ◽

Phenotype Analysis ◽

High Level

Abstract The MSH1 and MSH2 genes of Saccharomyces cerevisiae are predicted to encode proteins that are homologous to the Escherichia coli MutS and Streptococcus pneumoniae HexA proteins and their homologs. Disruption of the MSH1 gene caused a petite phenotype which was established rapidly. A functional MSH1 gene present on a single-copy centromere plasmid was incapable of rescuing the established msh1 petite phenotype. Analysis of msh1 strains demonstrated that mutagenesis and large-scale rearrangement of mitochondrial DNA had occurred. 4',6-Diamidino-2-phenylindole (DAPI) staining of msh1 yeast revealed an aberrant distribution of mtDNA. Haploid msh2 mutants displayed an increase of 85-fold in the rate of spontaneous mutation to canavanine resistance. Sporulation of homozygous msh2/msh2 diploids gave rise to a high level of lethality which was compounded during increased vegetative growth prior to sporulation. msh2 mutations also affected gene conversion of two HIS4 alleles. The his4x mutation, lying near the 5' end of the gene, was converted with equal frequency in both wild-type and msh2 strains. However, many of the events in the msh2 background were post-meiotic segregation (PMS) events (46.4%) while none (< 0.25%) of the aberrant segregations in wild type were PMS events. The his4b allele, lying 1.6 kb downstream of his4x, was converted at a 10-fold higher frequency in the msh2 background than in the corresponding wild-type strain. Like the his4x allele, his4b showed a high level of PMS (30%) in the msh2 background compared to the corresponding wild-type strain where no (< 0.26%) PMS events were observed. These results indicate that MSH1 plays a role in repair or stability of mtDNA and MSH2 plays a role in repair of 4-bp insertion/deletion mispairs in the nucleus.

Download Full-text

The Monarch Initiative: An integrative data and analytic platform connecting phenotypes to genotypes across species

10.1101/055756 ◽

2016 ◽

Author(s):

Christopher J Mungall ◽

Julie A McMurry ◽

Sebastian Köhler ◽

James P. Balhoff ◽

Charles Borromeo ◽

...

Keyword(s):

Large Scale ◽

Single Species ◽

Cellular Level ◽

Data Types ◽

Phenotypic Data ◽

Computational Tools ◽

Multimodal Data ◽

Phenotype Analysis ◽

Big Picture ◽

Single Data

AbstractThe principles of genetics apply across the whole tree of life: on a cellular level, we share mechanisms with species from which we diverged millions or even billions of years ago. We can exploit this common ancestry at the level of sequences, but also in terms of observable outcomes (phenotypes), to learn more about health and disease for humans and all other species. Applying the range of available knowledge to solve challenging disease problems requires unified data relating genomics, phenotypes, and disease; it also requires computational tools that leverage these multimodal data to inform interpretations by geneticists and to suggest experiments. However, the distribution and heterogeneity of databases is a major impediment: databases tend to focus either on a single data type across species, or on single species across data types. Although each database provides rich, high-quality information, no single one provides unified data that is comprehensive across species, biological scales, and data types. Without a big-picture view of the data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) is an international consortium dedicated to providing computational tools that leverage a computational representation of phenotypic data for genotype-phenotype analysis, genomic diagnostics, and precision medicine on the basis of a large-scale platform of multimodal data that is deeply integrated across species and covering broad areas of disease.

Download Full-text

methylSCOPA and META-methylSCOPA: software for the analysis and aggregation of epigenome-wide association studies of multiple correlated phenotypes

10.1101/656918 ◽

2019 ◽

Author(s):

Harmen Draisma ◽

Jun Liu ◽

Igor Pupko ◽

Ayşe Demirkan ◽

Zhanna Balkhiyarova ◽

...

Keyword(s):

Large Scale ◽

Smoking Status ◽

Association Studies ◽

Meta Analysis ◽

Serum Triglyceride ◽

Genome Wide Association Studies ◽

Birth Cohorts ◽

Total N ◽

Phenotype Analysis ◽

Genomic Locations

AbstractBackgroundMulti-phenotype genome-wide association studies (MP-GWAS) of correlated traits have greater power to detect genotype–phenotype associations than single-trait GWAS. However, no multi-phenotype analysis method exists for epigenome-wide association studies (EWAS).ResultsWe extended the SCOPA approach developed by us to “methylSCOPA” software in C++ by ‘reversely’ regressing DNA hyper/hypo-methylation information on a linear combination of phenotypes. We evaluated two models of association between DNA methylation and fasting glucose (FG) and insulin (FI) levels: Model 1, including FG, FI, and three measured potential confounders (body mass index [BMI], fasting serum triglyceride levels [TG], and waist/hip ratio [WHR]), and Model 2, including FG and FI corrected for the effects of BMI, TG, and WHR. Both models were additionally corrected for participant sex and smoking status (current/ever/never). We meta-analyzed the cohort-specific MP-EWAS results with our novel software META-methylSCOPA, mapped genomic locations to CGCh37/hg19, and adopted P<1×10−7 to denote epigenome-wide significance. We used the Illumina Infinium HumanMethylation450K BeadChip array data from the Northern Finland Birth Cohorts (NFBC) 1966/1986. We quality-controlled the data, regressed out the effects of measured potential confounders, and normalized the methylation signal intensity and FI data. The MP-EWAS included data for 643/457 individuals from NFBC1966 and NFBC1986, respectively (total N=1,100).In Model 1, we detected epigenome-wide significant association in the MP-EWAS meta-analysis at cg13708645 (chr12:121,974,305; P=1.2×10−8) within KDM2B gene. Single-trait effects within KDM2B were on FI, BMI, and WHR. Model with effect on BMI and WHR showed the strongest association at this locus, while effect on FI in single-phenotype analysis was driven by the effect of adiposity. In Model 2, the strongest association was at cg05063096 (chr3:143,689,810; P=2.3×10−7) annotated to C3orf58 with strongest effect on FI in single-trait analysis and multi-phenotype effect on FI and WHI within Model 1.We characterized the effects of established EWAS loci for diabetes and its risk factors and detected suggestive (p<0.01) associations at six markers including PHGDH, TXNIP, SLC7A11, CPT1A, MYO5C and ABCG1, through the dissection of the multi-phenotype effects in Model 1.ConclusionsWe implemented MP-EWAS in methylSCOPA and demonstrated its enhanced power over single-trait EWAS for correlated phenotypes in large-scale data.

Download Full-text

Some comments about observations and image processing of comet 29P/Schwassmann-Wachmann 1

International Astronomical Union Colloquium ◽

10.1017/s0252921100031493 ◽

1999 ◽

Vol 173 ◽

pp. 243-248

Author(s):

D. Kubáček ◽

A. Galád ◽

A. Pravda

Keyword(s):

Image Processing ◽

Large Scale ◽

Harvard College ◽

Oak Ridge ◽

Large Scale Structures ◽

Short Period Comet ◽

Short Period ◽

Scale Structures ◽

Harvard College Observatory ◽

Period Comet

AbstractUnusual short-period comet 29P/Schwassmann-Wachmann 1 inspired many observers to explain its unpredictable outbursts. In this paper large scale structures and features from the inner part of the coma in time periods around outbursts are studied. CCD images were taken at Whipple Observatory, Mt. Hopkins, in 1989 and at Astronomical Observatory, Modra, from 1995 to 1998. Photographic plates of the comet were taken at Harvard College Observatory, Oak Ridge, from 1974 to 1982. The latter were digitized at first to apply the same techniques of image processing for optimizing the visibility of features in the coma during outbursts. Outbursts and coma structures show various shapes.

Download Full-text

Evolution of Large-Scale Coronal Structures

International Astronomical Union Colloquium ◽

10.1017/s0252921100024945 ◽

1994 ◽

Vol 144 ◽

pp. 29-33

Author(s):

P. Ambrož

Keyword(s):

Magnetic Field ◽

Field Line ◽

Large Scale ◽

Coronal Magnetic Field ◽

Source Surface ◽

Solar Cycles ◽

Characteristic Relationship ◽

The Magnetic Field ◽

Coronal Structures

AbstractThe large-scale coronal structures observed during the sporadically visible solar eclipses were compared with the numerically extrapolated field-line structures of coronal magnetic field. A characteristic relationship between the observed structures of coronal plasma and the magnetic field line configurations was determined. The long-term evolution of large scale coronal structures inferred from photospheric magnetic observations in the course of 11- and 22-year solar cycles is described.Some known parameters, such as the source surface radius, or coronal rotation rate are discussed and actually interpreted. A relation between the large-scale photospheric magnetic field evolution and the coronal structure rearrangement is demonstrated.

Download Full-text

Large-scale Motion of Solar Filaments

International Astronomical Union Colloquium ◽

10.1017/s0252921100064502 ◽

2000 ◽

Vol 179 ◽

pp. 205-208

Author(s):

Pavel Ambrož ◽

Alfred Schroll

Keyword(s):

Magnetic Flux ◽

Proper Motion ◽

Time Scale ◽

Large Scale ◽

Accuracy Of Measurements ◽

Solar Filaments ◽

General Movement ◽

Scale Motion ◽

Velocity Scatter

AbstractPrecise measurements of heliographic position of solar filaments were used for determination of the proper motion of solar filaments on the time-scale of days. The filaments have a tendency to make a shaking or waving of the external structure and to make a general movement of whole filament body, coinciding with the transport of the magnetic flux in the photosphere. The velocity scatter of individual measured points is about one order higher than the accuracy of measurements.

Download Full-text

Some applications of electron beam microanalysis techniques in VLSI process evaluation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007463x ◽

1983 ◽

Vol 41 ◽

pp. 160-161

Author(s):

Simon Thomas

Keyword(s):

Integrated Circuits ◽

Process Evaluation ◽

Large Scale ◽

Technology Development ◽

Analytical Techniques ◽

Successful Implementation ◽

Analysis Of Failures ◽

Characterization Of Materials ◽

Circuits Vlsi

Trends in the technology development of very large scale integrated circuits (VLSI) have been in the direction of higher density of components with smaller dimensions. The scaling down of device dimensions has been not only laterally but also in depth. Such efforts in miniaturization bring with them new developments in materials and processing. Successful implementation of these efforts is, to a large extent, dependent on the proper understanding of the material properties, process technologies and reliability issues, through adequate analytical studies. The analytical instrumentation technology has, fortunately, kept pace with the basic requirements of devices with lateral dimensions in the micron/ submicron range and depths of the order of nonometers. Often, newer analytical techniques have emerged or the more conventional techniques have been adapted to meet the more stringent requirements. As such, a variety of analytical techniques are available today to aid an analyst in the efforts of VLSI process evaluation. Generally such analytical efforts are divided into the characterization of materials, evaluation of processing steps and the analysis of failures.

Download Full-text

Electron microscopy study of reactively sputter-deposited Ti/N films on silicon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100131449 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1362-1363

Author(s):

V. C. Kannan ◽

A. K. Singh ◽

R. B. Irwin ◽

S. Chittipeddi ◽

F. D. Nkansah ◽

...

Keyword(s):

Integrated Circuits ◽

Large Scale ◽

Hexagonal Phase ◽

Microscopy Study ◽

Electron Microscopy Study ◽

Process Conditions ◽

Tin Films ◽

Wide Range ◽

Fcc Phase ◽

Circuits Vlsi

Titanium nitride (TiN) films have historically been used as diffusion barrier between silicon and aluminum, as an adhesion layer for tungsten deposition and as an interconnect material etc. Recently, the role of TiN films as contact barriers in very large scale silicon integrated circuits (VLSI) has been extensively studied. TiN films have resistivities on the order of 20μ Ω-cm which is much lower than that of titanium (nearly 66μ Ω-cm). Deposited TiN films show resistivities which vary from 20 to 100μ Ω-cm depending upon the type of deposition and process conditions. TiNx is known to have a NaCl type crystal structure for a wide range of compositions. Change in color from metallic luster to gold reflects the stabilization of the TiNx (FCC) phase over the close packed Ti(N) hexagonal phase. It was found that TiN (1:1) ideal composition with the FCC (NaCl-type) structure gives the best electrical property.

Download Full-text