Full Text Journal Articles by
Author David Botstein

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Fully Phased Sequence of a Diploid Human Genome Determined de Novo from the DNA of a Single Individual.

Ilya Soifer, Nicole L Fong, Nelda Yi, Andrea T Ireland, Irene Lam, Matthew Sooknah, Jonathan S Paw, Paul Peluso, Gregory T Concepcion, David Rank, Alex R Hastie, Vladimir Jojic, J Graham Ruby, David Botstein, Margaret A Roy,

In recent years, improved sequencing technology and computational tools have made de novo genome assembly more accessible. Many approaches, however, generate either an unphased or only partially resolved representation of a diploid genome, in which polymorphisms are detected but not assigned to one or the other of the homologous chromosomes. ... Read more >>

G3 (Bethesda) (G3 (Bethesda, Md.))
[2020, :]

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A tps1Δ persister-like state in Saccharomyces cerevisiae is regulated by MKT1.

Patrick A Gibney, Anqi Chen, Ariel Schieler, Jonathan C Chen, Yifan Xu, David G Hendrickson, R Scott McIsaac, Joshua D Rabinowitz, David Botstein,

Trehalose metabolism in yeast has been linked to a variety of phenotypes, including heat resistance, desiccation tolerance, carbon-source utilization, and sporulation. The relationships among the several phenotypes of mutants unable to synthesize trehalose are not understood, even though the pathway is highly conserved. One of these phenotypes is that tps1Δ ... Read more >>

PLoS ONE (PloS one)
[2020, 15(5):e0233779]

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Minor Isozymes Tailor Yeast Metabolism to Carbon Availability.

Patrick H Bradley, Patrick A Gibney, David Botstein, Olga G Troyanskaya, Joshua D Rabinowitz,

Isozymes are enzymes that differ in sequence but catalyze the same chemical reactions. Despite their apparent redundancy, isozymes are often retained over evolutionary time, suggesting that they contribute to fitness. We developed an unsupervised computational method for identifying environmental conditions under which isozymes are likely to make fitness contributions. This ... Read more >>

mSystems (mSystems)
[2019, 4(1):]

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Minor isozymes tailor yeast metabolism to carbon availability

Patrick Bradley, Patrick Gibney, David Botstein, Olga Troyanskaya, Joshua Rabinowitz,

Abstract Isozymes are enzymes that differ in sequence but catalyze the same chemical reactions. Despite their apparent redundancy, isozymes are often retained over evolutionary time for reasons that can be unclear. We find that, in yeast, isozymes are strongly enriched in central carbon metabolism. Using a gene expression compendium, we ... Read more >>

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The future of humans as model organisms.

Garret FitzGerald, David Botstein, Robert Califf, Rory Collins, Keith Peters, Nick Van Bruggen, Dan Rader,

Science (Science (New York, N.Y.))
[2018, 361(6402):552-553]

Cited: 1 time

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Simultaneous Profiling of DNA Accessibility and Gene Expression Dynamics with ATAC-Seq and RNA-Seq.

David G Hendrickson, Ilya Soifer, Bernd J Wranik, David Botstein, R Scott McIsaac,

This chapter describes sequencing-based methods for profiling dynamic changes in DNA accessibility and gene expression in Saccharomyces cerevisiae. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) is a powerful technique for identifying nucleosome-free regions of the genome. Combining ATAC-Seq with RNA Sequencing (RNA-Seq) is a rapid approach for studying the ... Read more >>

Methods Mol. Biol. (Methods in molecular biology (Clifton, N.J.))
[2018, 1819:317-333]

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Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells.

Henrik D Møller, Rasmus K Bojsen, Chris Tachibana, Lance Parsons, David Botstein, Birgitte Regenberg,

Extrachromosomal circular DNAs (eccDNAs) are common genetic elements in Saccharomyces cerevisiae and are reported in other eukaryotes as well. EccDNAs contribute to genetic variation among somatic cells in multicellular organisms and to evolution of unicellular eukaryotes. Sensitive methods for detecting eccDNA are needed to clarify how these elements affect genome ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2016, (110):e54239 |]

Cited: 6 times

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Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in Saccharomyces cerevisiae.

Caitlin T Reavey, Mark J Hickman, Krista C Dobi, David Botstein, Fred Winston,

Studies of natural populations of many organisms have shown that traits are often complex, caused by contributions of mutations in multiple genes. In contrast, genetic studies in the laboratory primarily focus on studying the phenotypes caused by mutations in a single gene. However, the single mutation approach may be limited ... Read more >>

Genetics (Genetics)
[2015, 201(2):599-612]

Cited: 10 times

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Characterizing the in vivo role of trehalose in Saccharomyces cerevisiae using the AGT1 transporter.

Patrick A Gibney, Ariel Schieler, Jonathan C Chen, Joshua D Rabinowitz, David Botstein,

Trehalose is a highly stable, nonreducing disaccharide of glucose. A large body of research exists implicating trehalose in a variety of cellular phenomena, notably response to stresses of various kinds. However, in very few cases has the role of trehalose been examined directly in vivo. Here, we describe the development ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2015, 112(19):6116-6121]

Cited: 22 times

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Lasker∼Koshland to genetics pioneer.

David Botstein,

The 2014 Lasker∼Koshland Special Achievement Award will be presented to Mary-Claire King, a pioneer and visionary who revolutionized the use of genetics to identify disease genes, provide insights into human evolution, and champion human rights causes. ... Read more >>

Cell (Cell)
[2014, 158(6):1230-1232]

Cited: 0 times

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Synthetic biology tools for programming gene expression without nutritional perturbations in Saccharomyces cerevisiae.

R Scott McIsaac, Patrick A Gibney, Sunil S Chandran, Kirsten R Benjamin, David Botstein,

A conditional gene expression system that is fast-acting, is tunable and achieves single-gene specificity was recently developed for yeast. A gene placed directly downstream of a modified GAL1 promoter containing six Zif268 binding sequences (with single nucleotide spacing) was shown to be selectively inducible in the presence of β-estradiol, so ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2014, 42(6):e48]

Cited: 22 times

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Extensive Regulation of Metabolism and Growth during the Cell Division Cycle

Nikolai Slavov, David Botstein, Amy Caudy,

Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and ... Read more >>

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Rapid synthesis and screening of chemically activated transcription factors with GFP-based reporters.

R Scott McIsaac, Benjamin L Oakes, David Botstein, Marcus B Noyes,

Synthetic biology aims to rationally design and build synthetic circuits with desired quantitative properties, as well as provide tools to interrogate the structure of native control circuits. In both cases, the ability to program gene expression in a rapid and tunable fashion, with no off-target effects, can be useful. We ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2013, (81):e51153]

Cited: 4 times

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Yeast metabolic and signaling genes are required for heat-shock survival and have little overlap with the heat-induced genes.

Patrick A Gibney, Charles Lu, Amy A Caudy, David C Hess, David Botstein,

Genome-wide gene-expression studies have shown that hundreds of yeast genes are induced or repressed transiently by changes in temperature; many are annotated to stress response on this basis. To obtain a genome-scale assessment of which genes are functionally important for innate and/or acquired thermotolerance, we combined the use of a ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2013, 110(46):E4393-402]

Cited: 43 times

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Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations.

Gregory I Lang, Daniel P Rice, Mark J Hickman, Erica Sodergren, George M Weinstock, David Botstein, Michael M Desai,

The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance, the response of pathogens to immune selection, and the dynamics of cancer progression. In laboratory evolution ... Read more >>

Nature (Nature)
[2013, 500(7464):571-574]

Cited: 222 times

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Phylogenetic portrait of the Saccharomyces cerevisiae functional genome.

Patrick A Gibney, Mark J Hickman, Patrick H Bradley, John C Matese, David Botstein,

The genome of budding yeast (Saccharomyces cerevisiae) contains approximately 5800 protein-encoding genes, the majority of which are associated with some known biological function. Yet the extent of amino acid sequence conservation of these genes over all phyla has only been partially examined. Here we provide a more comprehensive overview and ... Read more >>

G3 (Bethesda) (G3 (Bethesda, Md.))
[2013, 3(8):1335-1340]

Cited: 2 times

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Genetic Basis of Ammonium Toxicity Resistance in a Sake Strain of Yeast: A Mendelian Case.

Cyrielle Reisser, Cynthia Dick, Leonid Kruglyak, David Botstein, Joseph Schacherer, David C Hess,

High concentrations of ammonium at physiological concentrations of potassium are toxic for the standard laboratory strain of Saccharomyces cerevisiae In the original description of this metabolic phenotype, we focused on the standard laboratory strains of Saccharomyces In this study, we screened a large collection of S. cerevisiae natural isolates and ... Read more >>

G3 (Bethesda) (G3 (Bethesda, Md.))
[2013, 3(4):733-740]

Cited: 4 times

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Visualization and analysis of mRNA molecules using fluorescence in situ hybridization in Saccharomyces cerevisiae.

R Scott McIsaac, Sanford J Silverman, Lance Parsons, Ping Xu, Ryan Briehof, Megan N McClean, David Botstein,

The Fluorescence in situ Hybridization (FISH) method allows one to detect nucleic acids in the native cellular environment. Here we provide a protocol for using FISH to quantify the number of mRNAs in single yeast cells. Cells can be grown in any condition of interest and then fixed and made ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2013, (76):e50382]

Cited: 6 times

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A new system for comparative functional genomics of Saccharomyces yeasts.

Amy A Caudy, Yuanfang Guan, Yue Jia, Christina Hansen, Chris DeSevo, Alicia P Hayes, Joy Agee, Juan R Alvarez-Dominguez, Hugo Arellano, Daniel Barrett, Cynthia Bauerle, Namita Bisaria, Patrick H Bradley, J Scott Breunig, Erin Bush, David Cappel, Emily Capra, Walter Chen, John Clore, Peter A Combs, Christopher Doucette, Olukunle Demuren, Peter Fellowes, Sam Freeman, Evgeni Frenkel, Daniel Gadala-Maria, Richa Gawande, David Glass, Samuel Grossberg, Anita Gupta, Latanya Hammonds-Odie, Aaron Hoisos, Jenny Hsi, Yu-Han Huang Hsu, Sachi Inukai, Konrad J Karczewski, Konrad J Karczewski, Xiaobo Ke, Mina Kojima, Samuel Leachman, Danny Lieber, Anna Liebowitz, Julia Liu, Yufei Liu, Trevor Martin, Jose Mena, Rosa Mendoza, Cameron Myhrvold, Christian Millian, Sarah Pfau, Sandeep Raj, Matt Rich, Joe Rokicki, William Rounds, Michael Salazar, Matthew Salesi, Rajani Sharma, Sanford Silverman, Cara Singer, Sandhya Sinha, Max Staller, Philip Stern, Hanlin Tang, Sharon Weeks, Maxwell Weidmann, Ashley Wolf, Carmen Young, Jie Yuan, Christopher Crutchfield, Megan McClean, Coleen T Murphy, Manuel Llinás, David Botstein, Olga G Troyanskaya, Maitreya J Dunham,

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum ... Read more >>

Genetics (Genetics)
[2013, 195(1):275-287]

Cited: 16 times

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TOR and RAS pathways regulate desiccation tolerance in Saccharomyces cerevisiae.

Aaron Z Welch, Patrick A Gibney, David Botstein, Douglas E Koshland,

Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible; only one in a million cells from an exponential culture survive desiccation compared with one in five cells in stationary phase. Here we exploit the desiccation sensitivity of exponentially dividing cells to understand the stresses imposed by desiccation and their ... Read more >>

Mol. Biol. Cell (Molecular biology of the cell)
[2013, 24(2):115-128]

Cited: 19 times

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Why we need more basic biology research, not less.

David Botstein,

Much of the spectacular progress in biomedical science over the last half-century is the direct consequence of the work of thousands of basic scientists whose primary goal was understanding of the fundamental working of living things. Despite this, many politicians, funders, and even scientists have come to believe that the ... Read more >>

Mol. Biol. Cell (Molecular biology of the cell)
[2012, 23(21):4160-4161]

Cited: 7 times

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Automating the construction of gene ontologies.

Kara Dolinski, David Botstein,

Nat. Biotechnol. (Nature biotechnology)
[2013, 31(1):34-35]

Cited: 8 times

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Synthetic gene expression perturbation systems with rapid, tunable, single-gene specificity in yeast.

R Scott McIsaac, Benjamin L Oakes, Xin Wang, Krysta A Dummit, David Botstein, Marcus B Noyes,

A general method for the dynamic control of single gene expression in eukaryotes, with no off-target effects, is a long-sought tool for molecular and systems biologists. We engineered two artificial transcription factors (ATFs) that contain Cys(2)His(2) zinc-finger DNA-binding domains of either the mouse transcription factor Zif268 (9 bp of specificity) ... Read more >>

Nucleic Acids Res. (Nucleic acids research)
[2013, 41(4):e57]

Cited: 50 times

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Combinatorial control of diverse metabolic and physiological functions by transcriptional regulators of the yeast sulfur assimilation pathway.

Allegra A Petti, R Scott McIsaac, Olivia Ho-Shing, Harmen J Bussemaker, David Botstein,

Methionine abundance affects diverse cellular functions, including cell division, redox homeostasis, survival under starvation, and oxidative stress response. Regulation of the methionine biosynthetic pathway involves three DNA-binding proteins-Met31p, Met32p, and Cbf1p. We hypothesized that there exists a "division of labor" among these proteins that facilitates coordination of methionine biosynthesis with ... Read more >>

Mol. Biol. Cell (Molecular biology of the cell)
[2012, 23(15):3008-3024]

Cited: 18 times

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Decoupling nutrient signaling from growth rate causes aerobic glycolysis and deregulation of cell size and gene expression.

Nikolai Slavov, David Botstein,

To survive and proliferate, cells need to coordinate their metabolism, gene expression, and cell division. To understand this coordination and the consequences of its failure, we uncoupled biomass synthesis from nutrient signaling by growing, in chemostats, yeast auxotrophs for histidine, lysine, or uracil in excess of natural nutrients (i.e., sources ... Read more >>

Mol. Biol. Cell (Molecular biology of the cell)
[2013, 24(2):157-168]

Cited: 18 times

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