Functional genomics articles within Nature Communications

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  • Article
    | Open Access

    The fungal Ascomycota provide a model phylum to investigate the evolution of complex multicellularity. Here, the authors combine genome sequencing with comparative and functional genomics to identify diverse endomembrane related machineries associated with the gain and loss of fungal complexity.

    • Tu Anh Nguyen
    • , Ousmane H. Cissé
    •  & Gregory Jedd

  • Article
    | Open Access

    Duchenne muscular dystrophy is a disease caused by a single gene, characterized by progressive muscle weakness, but is variable between patients partly due to interactions of other genes. Here, the authors show that a commonACTN3polymorphism can modify the clinical phenotype.

    • Marshall W. Hogarth
    • , Peter J. Houweling
    •  & Kathryn N. North

  • Article
    | Open Access

    Variations in the 17q21 locus are linked to asthma susceptibility and other autoimmune diseases. Here, the authors perform cell type-specific functional genomic analyses of asthma-risk SNPs, and show a genotype specific mechanism of differential gene regulation relevant to immune function.

    • Benjamin Joachim Schmiedel
    • , Grégory Seumois
    •  & Pandurangan Vijayanand

  • Article
    | Open Access

    Knockout collections provide a valuable tool to explore gene function, yet are expensive and technically challenging to produce at a genome-wide scale. Here Baym et al. devise a cost-effective transposon-based method to quickly develop a knockout collection for the electroactive microbe Shewanella oneidensis.

    • Michael Baym
    • , Lev Shaket
    •  & Buz Barstow

  • Article
    | Open Access

    Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

    • Paul K. Potter
    • , Michael R. Bowl
    •  & Steve D. M. Brown

  • Article
    | Open Access

    Binding of virus, HIV-1, to cellular protein Siglec-1 is important for infection of immune cells. Here the authors show that a natural mutation leading to production of truncated Siglec-1 reduces HIV binding and infectivity transfer in vitro, but does not substantially affect infection or AIDS outcome in patients.

    • Javier Martinez-Picado
    • , Paul J. McLaren
    •  & Amalio Telenti

  • Article
    | Open Access

    Plant-feeding insects of the Lygus genus have emerged as a major pest effecting cotton crops in the USA. Here the authors optimize the insecticidal activity of a Bacillus thuringiensis crystal protein and produce transgenic plants that are resistant to feeding damage by Lygusspecies.

    • Anilkumar Gowda
    • , Timothy J. Rydel
    •  & James A. Baum

  • Article
    | Open Access

    Identifying therapeutic targets in rare cancers is challenging due to the lack of relevant pre-clinical models. Here, the authors generate a cancer cell line from a paediatric patient with a rare undifferentiated sarcoma and through functional genomics and chemical screens identified CDK4 and XPO1 as potential therapeutic targets in this cancer.

    • Andrew L. Hong
    • , Yuen-Yi Tseng
    •  & Jesse S. Boehm

  • Article
    | Open Access

    Mutational signatures provide evidence of the mechanism of action of a given mutagen and are found in cancer cells. Here, using 560 breast cancer genomes, the authors demonstrate that mutational signatures are frequently associated with genomic architecture including nucleosome positioning and replication timing.

    • Sandro Morganella
    • , Ludmil B. Alexandrov
    •  & Serena Nik-Zainal

  • Article
    | Open Access

    Analysis of RNAi screens is a multi-step process requiring the sequential use of several unrelated resources. Here the authors generate an online resource integrating RNAi analytic tools and filters into a seamless workflow, which improves the specificity, selectivity and reproducibility of the results.

    • Bhaskar Dutta
    • , Alaleh Azhir
    •  & Iain D. C. Fraser

  • Article
    | Open Access

    Next generation sequencing allows the identification of oncogenic driver genes in pancreatic cancer. Here, in an effort to identify additional causal genes, the authors develop a high throughput in vivoscreen and identify genes that whilst infrequently mutated in pancreatic cancer contribute to tumour formation.

    • Yiu Huen Tsang
    • , Turgut Dogruluk
    •  & Kenneth L. Scott

  • Article
    | Open Access

    Drosophila RNAi libraries are commonly used to perform large-scale functional genetics screens in vivo. Here the authors find that a subset of lines from the VDRC KK RNAi line cause false-positive enhancement of the Hippo pathway, and provide a strain that can test whether a genetic screen of interest will be affected by this technical artefact.

    • Joseph H.A. Vissers
    • , Samuel A. Manning
    •  & Kieran F. Harvey

  • Article
    | Open Access

    Inducing random mutation of C. elegansDNA is a widely used technique to investigate gene and protein function. Here the authors introduce a method of optogenetic mutagenesis, driving the generation of reactive oxygen species, which avoids the use of toxic chemicals.

    • Kentaro Noma
    •  & Yishi Jin

  • Article
    | Open Access

    Colorectal cancer subtypes can be distinguished by their different biological and molecular properties. Here the authors present microRNA Master Regulator Analysis, a tool to identify microRNAs driving subtype-specific gene expression and cancer variation.

    • Laura Cantini
    • , Claudio Isella
    •  & Enzo Medico

  • Article
    | Open Access

    Short hairpin RNAs are widely used to produce small interfering RNAs (siRNAs) for gene silencing. Here, the authors show that an alternative siRNA precursor in the presence of a self-cleaving ribozyme has enhanced silencing activity and reduced off-target effects, providing a potential RNAi tool.

    • Renfu Shang
    • , Fengjuan Zhang
    •  & Ligang Wu

  • Article
    | Open Access

    Random DNA mutagenesis provides genetic diversity both in nature and the laboratory. Here, Badran and Liu present a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that surpasses the mutational efficiency and spectra of the most widely used in vivo and in vitromutagenesis methods.

    • Ahmed H. Badran
    •  & David R. Liu

  • Article
    | Open Access

    Phagocytes employ multiple bactericidal mechanisms to kill microorganisms, including the generation of toxic superoxide and other reactive oxygen species. Here the authors utilize a multi-omics approach to identify and characterize new regulatory nodes implicated in mucosal immunity that control phagocyte oxidative burst.

    • Daniel B. Graham
    • , Christine E. Becker
    •  & Ramnik J. Xavier

  • Article
    | Open Access

    Screening genomic or metagenomic libraries for interesting products or activities is often hampered by poor gene expression in a heterologous host. Here the authors show that the expression of a Lactobacillus sigma factor greatly enhances transcription of heterologous and environmental DNA in E. coli.

    • Stefan M. Gaida
    • , Nicholas R. Sandoval
    •  & Eleftherios T. Papoutsakis

  • Article
    | Open Access

    Cryptococcus neoformans is a fungal pathogen that causes meningoencephalitis. Here the authors describe the production of a gene-deletion mutant collection representing most C. neoformansnon-essential transcription factors, providing insight into the signalling networks that govern the biology and pathogenicity of this fungus.

    • Kwang-Woo Jung
    • , Dong-Hoon Yang
    •  & Yong-Sun Bahn

  • Article |

    Microbial formate dehydrogenases (FDH) are molybdenum-containing enzymes that can catalyse the reduction of CO2 into formate. Here, the authors suggest a structural and functional basis for sulphuration of the molybdenum cofactor in E. coliFDH, a key step in the production of active formate dehydrogenase.

    • Pascal Arnoux
    • , Christian Ruppelt
    •  & Anne Walburger

  • Article
    | Open Access

    Terpene cyclases are ring-forming enzymes found in many biosynthetic pathways, but the evolutionary origins of the cyclization mechanism is not well understood. Here, the authors use structure-guided breeding to identify an epistatic network that controls the onset of cyclization activity in Artemisia annua.

    • Melissa Salmon
    • , Caroline Laurendon
    •  & Paul E. O’Maille

  • Article
    | Open Access

    Wilms tumour (WT) is the most common paediatric kidney cancer and few driver genes related to its development have been identified. Here, the authors identify DROSHAmutations that may contribute to WT tumorigenesis through their effect on primary microRNA processing.

    • Giovana T. Torrezan
    • , Elisa N. Ferreira
    •  & Dirce M. Carraro

  • Article
    | Open Access

    Rice false smut, caused by the pathogenic ascomycete fungus Ustilaginoidea virens (Cooke) Takah, has a significant economic impact on crop production. Here, Zhang et al. report the draft genome sequence of U. virensand provide insight into the evolution of genes involved in pathogenicity and adaptation to a biotrophic and floret-infecting lifestyle.

    • Yong Zhang
    • , Kang Zhang
    •  & Wenxian Sun

  • Article |

    Macromolecular complexes hold promise for future generations of drug delivery carriers, but probing their structures with high resolution is challenging. Here, the authors combine X-ray free-electron laser and synchrotron approaches to reveal the core-shell structure of RNA interference microsponges.

    • Marcus Gallagher-Jones
    • , Yoshitaka Bessho
    •  & Changyong Song

  • Article |

    Defects in the homologous recombination repair of DNA can result in gene mutation and cancer. In this study, Peng et al.identify a gene signature associated with homologous recombination repair deficiency and show that this can be used both to predict repair defects and clinical outcome in cancer patients.

    • Guang Peng
    • , Curtis Chun-Jen Lin
    •  & Shiaw-Yih Lin

  • Article |

    RNA can be silenced in a sequence-specific manner but whether proteins can silence RNA in this way is unknown. Now, Yamaguchi and colleagues show that an enzyme isolated fromHaloquadra walsbyi cleaves 7-base-pair sequences in Escherichia coli, and this high sequence specificity permits the silencing of targeted genes.

    • Yoshihiro Yamaguchi
    • , Hirofumi Nariya
    •  & Masayori Inouye

  • Article |

    During development, Wnt-mediated Notch signalling controls the generation of somites from the presomitic mesoderm, but the precise signalling mechanism is unknown. Here, the transcription factor Mesogenin 1 is shown to be a direct target of Wnt3a and regulates the transcription of a Notch signalling program.

    • Ravindra B. Chalamalasetty
    • , William C. Dunty Jr
    •  & Terry P. Yamaguchi

  • Article
    | Open Access

    Identifying the transcripts and proteins that fluctuate in response to stimuli provides important information for understanding cell physiology. In this study, 52% of theBacillus subtilispredicted proteome is identified following glucose starvation, revealing further insight into protein dynamics at a global scale.

    • Andreas Otto
    • , Jörg Bernhardt
    •  & Dörte Becher

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