Signature-tagged mutagenesis: barcoding mutants for genome-wide screens

DNA signature tags (molecular barcodes) facilitate functional screens by identifying mutants in mixed populations that have a reduced or increased adaptation to a particular environment. Many innovative adaptations and refinements in the technology have been described since its original use with Salmonella; they have yielded a wealth of information on a broad range of biological processes — mainly in bacteria, but also in yeast and other fungi, viruses, parasites and, most recently, in mammalian cells. By combining whole-genome microarrays and comprehensive ordered libraries of mutants, high-throughput functional screens can now be achieved on a genomic scale.

[1]  L. Chin,et al.  A Genetic Screen for Candidate Tumor Suppressors Identifies REST , 2005, Cell.

[2]  E. Winzeler,et al.  Application of High-Density Array-Based Signature-Tagged Mutagenesis To Discover Novel YersiniaVirulence-Associated Genes , 2001, Infection and Immunity.

[3]  Ronald W. Davis,et al.  Mechanisms of Haploinsufficiency Revealed by Genome-Wide Profiling in Yeast , 2005, Genetics.

[4]  Nathaniel J. Moorman,et al.  Identification of Candidate Gammaherpesvirus 68 Genes Required for Virus Replication by Signature-Tagged Transposon Mutagenesis , 2004, Journal of Virology.

[5]  X. Nassif,et al.  Large-scale analysis of the meningococcus genome by gene disruption: resistance to complement-mediated lysis. , 2003, Genome research.

[6]  Brigitte Gicquel,et al.  Production of phthiocerol dimycocerosates protects Mycobacterium tuberculosis from the cidal activity of reactive nitrogen intermediates produced by macrophages and modulates the early immune response to infection , 2004, Cellular microbiology.

[7]  Reuven Agami,et al.  A large-scale RNAi screen in human cells identifies new components of the p53 pathway , 2004, Nature.

[8]  D. Maskell,et al.  Signature-Tagged Transposon Mutagenesis Studies Demonstrate the Dynamic Nature of Cecal Colonization of 2-Week-Old Chickens by Campylobacter jejuni , 2005, Applied and Environmental Microbiology.

[9]  M. Frosch,et al.  Identification of a hotspot for transformation of Neisseria meningitidis by shuttle mutagenesis using signature-tagged transposons , 1998, Molecular and General Genetics MGG.

[10]  Elizabeth A. Winzeler,et al.  Genomic profiling of drug sensitivities via induced haploinsufficiency , 1999, Nature Genetics.

[11]  D Botstein,et al.  Genetic footprinting: a genomic strategy for determining a gene's function given its sequence. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Floyd E Romesberg,et al.  Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Christoph Dehio,et al.  Signature-tagged mutagenesis: technical advances in a negative selection method for virulence gene identification. , 2005, Current opinion in microbiology.

[14]  B. Gicquel,et al.  Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature‐tagged transposon mutagenesis , 1999, Molecular microbiology.

[15]  C. Rogler,et al.  Multi-miRNA hairpin method that improves gene knockdown efficiency and provides linked multi-gene knockdown. , 2006, BioTechniques.

[16]  J. Boeke,et al.  A DNA Microarray-Based Genetic Screen for Nonhomologous End-Joining Mutants in Saccharomyces cerevisiae , 2001, Science.

[17]  Ronald W. Davis,et al.  A genome-wide screen in Saccharomyces cerevisiae for genes affecting UV radiation sensitivity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Ronald W. Davis,et al.  Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar–coding strategy , 1996, Nature Genetics.

[19]  M. Parrish,et al.  Parallel analysis of tagged deletion mutants efficiently identifies genes involved in endoplasmic reticulum biogenesis , 2003, Yeast.

[20]  J. Pringle,et al.  Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[21]  A. Darwin,et al.  Identification of Yersinia enterocolitica genes affecting survival in an animal host using signature‐tagged transposon mutagenesis , 1999, Molecular microbiology.

[22]  W. Hufnagle,et al.  Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments , 1998, Molecular microbiology.

[23]  Ronald W. Davis,et al.  Systematic screen for human disease genes in yeast , 2002, Nature Genetics.

[24]  D. Holden,et al.  Identification of Staphylococcus aureus virulence genes in a murine model of bacteraemia using signature‐tagged mutagenesis , 1997, Molecular microbiology.

[25]  Christoph M Tang,et al.  Functional genomics of Neisseria meningitidis pathogenesis , 2000, Nature Medicine.

[26]  H. Arst,et al.  Signature‐tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity , 2000, Molecular microbiology.

[27]  Liming Yang,et al.  A loss-of-function RNA interference screen for molecular targets in cancer , 2006, Nature.

[28]  D. Simon,et al.  Large-scale identification of virulence genes from Streptococcus pneumoniae. , 1998, Infection and immunity.

[29]  R. Haas,et al.  Identification and Characterization of Helicobacter pylori Genes Essential for Gastric Colonization , 2003, The Journal of experimental medicine.

[30]  B. Beutler,et al.  Analysis of the MCMV resistome by ENU mutagenesis , 2006, Mammalian Genome.

[31]  W. Bishai,et al.  Designer Arrays for Defined Mutant Analysis To Detect Genes Essential for Survival of Mycobacterium tuberculosis in Mouse Lungs , 2005, Infection and Immunity.

[32]  A. Camilli,et al.  Large‐scale identification of serotype 4 Streptococcus pneumoniae virulence factors , 2002, Molecular microbiology.

[33]  A. Charbit,et al.  Lessons from signature-tagged mutagenesis on the infectious mechanisms of pathogenic bacteria. , 2005, FEMS microbiology reviews.

[34]  Ronald W Davis,et al.  Parallel phenotypic analysis of sporulation and postgermination growth in Saccharomyces cerevisiae , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Mark P Stevens,et al.  Identification of host‐specific colonization factors of Salmonella enterica serovar Typhimurium , 2004, Molecular microbiology.

[36]  Gary D Bader,et al.  Global Mapping of the Yeast Genetic Interaction Network , 2004, Science.

[37]  J. Boothroyd,et al.  Adaptation of signature-tagged mutagenesis for Toxoplasma gondii: a negative screening strategy to isolate genes that are essential in restrictive growth conditions. , 2001, Molecular and biochemical parasitology.

[38]  R. Levesque,et al.  Defined oligonucleotide tag pools and PCR screening in signature-tagged mutagenesis of essential genes from bacteria. , 1999, BioTechniques.

[39]  A. Chu,et al.  Use of a Genome-Wide Approach to Identify New Genes that Control Resistance of Saccharomyces cerevisiae to Ionizing Radiation , 2003, Radiation research.

[40]  Gary D Bader,et al.  Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants , 2001, Science.

[41]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[42]  Gavin Sherlock,et al.  Global analysis of gene function in yeast by quantitative phenotypic profiling , 2006, Molecular systems biology.

[43]  A. De Las Peñas,et al.  Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. , 2003, Genes & development.

[44]  S. Falkow,et al.  Efficient homologous and illegitimate recombination in the opportunistic yeast pathogen Candida glabrata. , 1999, Genetics.

[45]  J. Lodge,et al.  Identification of virulence mutants of the fungal pathogen Cryptococcus neoformans using signature-tagged mutagenesis. , 2001, Genetics.

[46]  Finbarr Hayes,et al.  Transposon-based strategies for microbial functional genomics and proteomics. , 2003, Annual review of genetics.

[47]  Stanley Falkow,et al.  Microarray-Based Detection of Salmonella enterica Serovar Typhimurium Transposon Mutants That Cannot Survive in Macrophages and Mice , 2005, Infection and Immunity.

[48]  Patrick J. Paddison,et al.  A resource for large-scale RNA-interference-based screens in mammals , 2004, Nature.

[49]  Christian Cambillau,et al.  LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis , 2006, The EMBO journal.

[50]  William R. Jacobs,et al.  Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice , 1999, Nature.

[51]  Seth Sadis,et al.  Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[52]  Stanley Falkow,et al.  Global Transposon Mutagenesis and Essential Gene Analysis of Helicobacter pylori , 2004, Journal of bacteriology.

[53]  S. L. Chiang,et al.  Use of signature‐tagged transposon mutagenesis to identify Vibrio cholerae genes critical for colonization , 1998, Molecular microbiology.

[54]  J. Borg,et al.  The Intracellular Fate of Salmonella Depends on the Recruitment of Kinesin , 2005, Science.

[55]  J. Bader,et al.  A robust toolkit for functional profiling of the yeast genome. , 2004, Molecular cell.

[56]  J. Boeke,et al.  DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray , 2003, Nature Genetics.

[57]  E. Moxon,et al.  Genetic analysis of Escherichia coli K1 gastrointestinal colonization , 2000, Molecular microbiology.

[58]  J. Shendure,et al.  Selection analyses of insertional mutants using subgenic-resolution arrays , 2001, Nature Biotechnology.

[59]  R. Perry,et al.  Unexpected results from the application of signature-tagged mutagenesis to identify Yersinia pestis genes required for adherence and invasion. , 2005, Microbial pathogenesis.

[60]  S. Falkow,et al.  Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[61]  I. Kukavica-Ibrulj,et al.  In vivo functional genomics of Pseudomonas aeruginosa for high-throughput screening of new virulence factors and antibacterial targets. , 2003, Environmental microbiology.

[62]  R. Sun,et al.  Identification of viral genes essential for replication of murine gamma-herpesvirus 68 using signature-tagged mutagenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[63]  J. C. Hinshaw,et al.  Discovering Modes of Action for Therapeutic Compounds Using a Genome-Wide Screen of Yeast Heterozygotes , 2004, Cell.

[64]  Samuel I. Miller,et al.  Identification of a Putative Salmonella enterica Serotype Typhimurium Host Range Factor with Homology to IpaH and YopM by Signature-Tagged Mutagenesis , 1999, Infection and Immunity.

[65]  Michael I. Jordan,et al.  Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Zhengfan Jiang,et al.  Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. , 2006, Annual review of immunology.

[67]  D. O’Callaghan,et al.  Identification of Brucella suis Genes Affecting Intracellular Survival in an In Vitro Human Macrophage Infection Model by Signature-Tagged Transposon Mutagenesis , 2000, Infection and Immunity.

[68]  René Bernards,et al.  An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors , 2006, Nature chemical biology.

[69]  Erik J. Sontheimer,et al.  Assembly and function of RNA silencing complexes , 2005, Nature Reviews Molecular Cell Biology.

[70]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[71]  Ronald W. Davis,et al.  Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[72]  Patrick J. Paddison,et al.  Second-generation shRNA libraries covering the mouse and human genomes , 2005, Nature Genetics.

[73]  S. Guadagnini,et al.  Optimization of Virulence Functions Through Glucosylation of Shigella LPS , 2005, Science.

[74]  Frederick M Ausubel,et al.  Correction for Liberati et al., An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants , 2006, Proceedings of the National Academy of Sciences.

[75]  Roger A. Jones,et al.  A glutamate‐alanine‐leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP , 2005, Molecular microbiology.

[76]  E. Hanski,et al.  A locus of group A streptococcus involved in invasive disease and DNA transfer , 2002, Molecular microbiology.

[77]  H. Bussey,et al.  Large‐scale essential gene identification in Candida albicans and applications to antifungal drug discovery , 2003, Molecular microbiology.

[78]  Zuoshang Xu,et al.  Multiple shRNAs expressed by an inducible pol II promoter can knock down the expression of multiple target genes. , 2006, BioTechniques.

[79]  Inmar E. Givoni,et al.  Exploring the Mode-of-Action of Bioactive Compounds by Chemical-Genetic Profiling in Yeast , 2006, Cell.

[80]  Songyan Liu,et al.  The International Gene Trap Consortium Website: a portal to all publicly available gene trap cell lines in mouse , 2005, Nucleic Acids Res..

[81]  J. Mecsas Use of signature-tagged mutagenesis in pathogenesis studies. , 2002, Current opinion in microbiology.

[82]  J. O’Neill,et al.  Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers. , 2006, Vaccine.

[83]  MJ Mahan,et al.  Selection of bacterial virulence genes that are specifically induced in host tissues , 1993, Science.

[84]  M. Lonetto,et al.  A functional genomic analysis of type 3 Streptococcus pneumoniae virulence , 2001, Molecular microbiology.

[85]  J. Shea,et al.  Simultaneous identification of bacterial virulence genes by negative selection. , 1995, Science.

[86]  Robert P. St.Onge,et al.  Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents , 2005, PLoS genetics.

[87]  W. Jacobs,et al.  Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening , 2004, Infection and Immunity.

[88]  M. Rasmussen,et al.  Identification of Salmonella enterica Serovar Typhimurium Genes Important for Survival in the Swine Gastric Environment , 2006, Applied and Environmental Microbiology.

[89]  Jennifer L. Groh,et al.  A Method Adapting Microarray Technology for Signature-Tagged Mutagenesis of Desulfovibrio desulfuricans G20 and Shewanella oneidensis MR-1 in Anaerobic Sediment Survival Experiments , 2005, Applied and Environmental Microbiology.

[90]  E. Rubin,et al.  Comprehensive identification of conditionally essential genes in mycobacteria , 2001, Proceedings of the National Academy of Sciences of the United States of America.