Functional genomics articles within Nature Communications

Sequestering mRNA in cytoplasmic stress granules is a mechanism for translational repression. Here the authors find that p53 mRNA, present in stress granules in activated B lymphocytes, is released upon DNA damage and is translated in a CAP-independent manner.

The molecular mechanisms mediating the impact of environmental factors in atherosclerosis are unclear. Here, the authors examine CD14+ blood monocyte’s transcriptome and epigenome signatures to find differential methylation and expression of ARID5B to be associated with human atherosclerosis.

Insight into the genetic influence on the immune response is important for the understanding of interindividual variability in human pathologies. Here, the authors generate transcriptome data from human blood monocytes stimulated with various immune stimuli and provide a time-resolved response eQTL map.

Numerous genetic variants, including those located in the non-coding regions of the genome, are known to be associated with blood cells traits. Here, Frontini and colleagues investigate their potential regulatory functions using epigenomic data and promoter long-range interactions.

Isolated populations often have special genetic compositions that can be leveraged for genetic association studies. Here, Xue and colleagues generate and analyse 3,059 low-depth whole-genome sequences from eight European isolated populations and two matched general populations.

Protein-protein interactions (PPIs) play a major role in defining biological functions. Here, the authors present PPiSeq, a method to quantitatively score dynamic PPIs in yeast combining fragment complementation assays, genomic double-barcoding, and an analytical framework to precisely call fitness from barcode lineage trajectories.

CRISPR-Cas9 has been utilized to screen the genome in loss-of-function studies to identify genetic interactions. Here the authors compare catalytically active and dead Cas9 and observe different off-target effects in a screen for essential genes.

Transcriptome sequencing is a powerful tool for functional analysis of different types of RNA molecules in a wide range of applications. Here the authors use targeted resequencing of cDNA with single-molecule molecular inversion probes as a cost-effective, high-throughput tool for mRNA quantification.

CRISPR-Cas9 screens are powerful high-throughput tools but can be confounded by nuclease toxicity. Here the authors design a library of variable length gRNAs with thousands of negative controls, including the targeting of ‘safe’ loci to account for on-target site DNA damage toxicity.

Risk for the paediatric cancer high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) has been associated with genetic variants at 10q21.2. Here, the authors characterize this region, establishing a single risk variant and showing its role in dysregulated expression ofARID5B.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease resulting in reduced mucus clearance and impaired lung function. Here, the authors show that mutations in PIH1D3 are responsible for an X-linked form of PCD, affecting assembly of a subset of inner arm dyneins.

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.

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.

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.

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.

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.

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.

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.

Coronary heart disease is the leading cause of death worldwide with multiple environmental and genetic risk factors. Here the authors integrate genomic, epigenomic and transcriptomic mapping to elucidate causal variation and mechanisms of known genetic associations.

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.

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.

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.

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.

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.

Type 2 CD8⁺ T cells (Tc2) play a role in the development of experimental asthma. Here the authors show that 1,25D3, the active form of vitamin D3, can prevent conversion of CD8⁺T cells to a Tc2 phenotype, reducing asthma susceptibility.

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.

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.

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.

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.

Unbiased screening for insect gene function has been largely restricted to Drosophila. Here, Schmitt-Engel et al. perform an unbiased large-scale RNAi screen in the red flour beetle Tribolium castaneumto identify putative gene functions.

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.

DNA double-stranded breaks can be repaired through error-prone pathways. Here, van Schendel et al. demonstrate that C. elegansacquires inheritable mutations through the use of polymerase theta-mediated end joining.

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.

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.

Profiling pluripotent stem cell (PSC)-derived neural progeny is of fundamental interest for characterizing stem cell differentiation. Here, the authors analyse neural progenitors consecutively derived from human PSCs, showing dynamic stage-specific transcriptional patterns for distinct neural progenitors.

Accumulation of mitochondrial DNA (mtDNA) mutations is linked to severe anaemia by an unknown mechanism. Here the authors show that excessive mtDNA mutations impair mitochondrial expulsion during erythropoiesis leading to augmented erythrocyte clearance and anaemia in mice and humans.

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.

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.

Identifying which genes and pathways explain genetic associations is challenging. Here, the authors present DEPICT, a tool for gene prioritization, pathway analysis and tissue/cell-type enrichment analysis that can be used to generate testable hypotheses from genetic association studies.

Rapid and stable manipulation of gene expression in the malarial parasite Plasmodium falciparum remains a significant challenge. Goldfless et al. adapt a system for the inducible control of mRNA translation for use in Plasmodiumand demonstrate its use to validate targets of antimalarial drugs.

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.

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.

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.

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.

The composition of trace elements in human cells (the ionome) is an important component of metabolism. Here, the authors carry out a high-throughput, genome-wide analysis of the human ionome and identify cellular regulators of important trace elements such as selenium, copper and iron.

Oleispira antarctica is an oil-degrading bacterium found in the cold and deep sea. Here Kube et al. report the genome sequence of O. antarcticaand provide a comprehensive functional genetic and protein structural analysis, revealing insights into how this organism has adapted to its cold environment.

Systemic infection with the fungal pathogenC. albicans is characterized by high mortality, and the precise antifungal defence mechanisms in humans are poorly defined. Using a systems approach, Smeekens et al. describe a previously unknown role for type I interferons in human anti-Candidadefence.

The cre-loxP system is widely used for the generation of conditional gene knockouts. Here Heffner et al.systematically characterize cre recombinase activity in tissues of embryonic and adult cre-driver mouse strains and provide an online resource for scientists.

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.