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Yungil Kim

Bio: Yungil Kim is an academic researcher from University of Minnesota. The author has contributed to research in topics: Synthetic genetic array & Genetic Fitness. The author has an hindex of 3, co-authored 5 publications receiving 2505 citations.

Papers
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Journal ArticleDOI
22 Jan 2010-Science
TL;DR: A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function.
Abstract: A genome-scale genetic interaction map was constructed by examining 5.4 million gene-gene pairs for synthetic genetic interactions, generating quantitative genetic interaction profiles for ~75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on genetic interaction profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets, and highly correlated profiles delineate specific pathways to define gene function. The global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification.

2,225 citations

Journal ArticleDOI
TL;DR: This work has applied the SGA score to examine the relationship between physical and genetic interaction networks, and found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.
Abstract: Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.

362 citations

Journal ArticleDOI
TL;DR: This work investigated the basis of robustness and tunability in the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis with a regularized multiple regression model, indicating a mechanism enabling tunability.

106 citations

Journal ArticleDOI
TL;DR: The preliminary results showed that the plant immune-signaling network genes are significantly enriched with genes whose Tajima’s D values are near zero compared with all of the genes in the genome, suggesting that there is a lower level of purifying selection among the network component genes than other genes.
Abstract: Arabidopsis thaliana is a member of the mustard (Brassicaceae) family that is widely used as a model organism in plant biology. The 1001 Genomes Project [1] has been sequencing the genomes of Arabidopsis strains (accessions) and has made these sequences available. We selected the genomes of 30 Arabidopsis accessions with diverse geographical and environmental origins for our analysis. Using the TAIR8 annotation of the Arabidopsis reference genome, for the accession Col-0, we generated a dataset of approximately 27,000 protein-coding genes for all of the 30 genomes. With such population genomic data, it is feasible to ask whether a group of genes is under a different type of selection from the rest of the genome. The plant immune-signaling network is robust to network perturbations. We hypothesized that genes that constitute a robust network tend to be under neutral selection because deleterious mutations in such genes do not strongly affect the immune phenotype owing to the robustness of the network. We identified the component genes of the plant immune-signaling network in a relatively unbiased manner by mining AraNet [2], which is a functional gene network built without using phenotype information. We compared population genetic summary statistics for the network component genes and those for all of the genes in the genome. For example, Tajima’s D is such a summary statistic, and positive, negative and zero values of Tajima’s D suggest diversifying, purifying and neutral selection, respectively, when the effective population size does not change. The Tajima’s D value distribution for all of the genes in the genome has a single clear peak with a negative value, suggesting that purifying selection is the genomic norm. Our preliminary results showed that the plant immune-signaling network genes are significantly enriched with genes whose Tajima’s D values are near zero compared with all of the genes in the genome. This finding suggests that there is a lower level of purifying selection among the network component genes than other genes.
Proceedings ArticleDOI
17 May 2009
TL;DR: This work has developed a strategy for highly quantitative characterization of interactions from Synthetic Genetic Arrays, and is now getting the first view of a large fraction of the yeast genetic interaction network.
Abstract: Understanding cellular organization and function on a global scale is a central challenge in systems biology. Recent high-throughput experimental technology has produced datasets capturing physical and genetic interactions among various components of the cell, which contain clues about systems-level organization. While the analysis of physical interaction networks has received significant attention from the bioinformatics community, relatively little attention has been devoted to analysis of the more general phenomenon of genetic interaction. Genetic interactions are generally defined as cases where simultaneous mutations in multiple genes result in a surprising phenotype, and are highly complementary to information in the physical interaction network. In collaboration with a yeast genetics lab, we have developed a strategy for highly quantitative characterization of interactions from Synthetic Genetic Arrays (SGA), and are now getting our first view of a large fraction of the yeast genetic interaction network. We will introduce several fundamental concepts supporting the emerging direction of genetic interaction networks and describe several striking properties revealed by mining the structure of such networks. For example, we will discuss the connection between modularity and genetic interactions, and describe the potential of these data for global characterization of network structure and robustness. We will highlight several open problems in the interpretation of such networks and discuss where innovations in machine learning and data mining are particularly relevant.

Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
03 Jan 2014-Science
TL;DR: In this paper, a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library was described.
Abstract: The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, whereas another for the DNA topoisomerase II ( TOP2A ) poison etoposide identified TOP2A , as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Last, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells.

2,487 citations

01 Dec 2013
TL;DR: A pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library is described and it is shown that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs.
Abstract: The bacterial CRISPR/Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, while another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Finally, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/ sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells.

2,130 citations

Journal ArticleDOI
23 Oct 2014-Cell
TL;DR: This work identifies rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators to endogenous genes via endonuclease-deficient Cas9, which enable modulation of gene expression over a ∼1,000-fold range.

2,041 citations

Journal ArticleDOI
21 Jan 2016-Nature
TL;DR: The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large as discussed by the authors, and the evolution and widespread distribution of antibiotic-resistant elements in bacterial pathogens has made diseases that were once easily treatable deadly again.
Abstract: The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

1,481 citations