Transcriptomics articles within Nature Communications

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  • Article
    | Open Access

    Predicting the hepatotoxic effects of new drugs is still a challenge. Using toxicogenomics data, the authors here define a predictive toxicogenomic space (PTGS), the component gene space capturing dose-dependent cytotoxicity, and demonstrate that it can be used to accurately predict drug-induced liver pathology, including human drug-induced liver injury fromin vitrodata.

    • Pekka Kohonen
    • , Juuso A. Parkkinen
    •  & Roland C. Grafström

  • Article
    | Open Access

    In animals with complex life cycles, selection on one life phase may constrain adaptation in another phase. Here the authors find that, during the adaptive radiation of mantellid frogs, the evolution of tadpole and adult morphologies has been uncoupled through phase-specific gene expression.

    • Katharina C. Wollenberg Valero
    • , Joan Garcia-Porta
    •  & Miguel Vences

  • Article
    | Open Access

    The mechanisms linking phenotypic heterogeneity to collective cancer invasion are unclear. Here the authors develop an image-guided genomic technique to select and amplify leader and follower cells fromin vitroinvading cell packs and find a cooperative symbiotic relationship between these two cell populations.

    • J. Konen
    • , E. Summerbell
    •  & A. I. Marcus

  • Article
    | Open Access

    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.

    • Peer Arts
    • , Jori van der Raadt
    •  & Cornelis A. Albers

  • Article
    | Open Access

    How neurons and neuronal activity regulate astrocyte functions is poorly understood. Haselet al. identify two large groups of astrocytic genes that are regulated by neuronal contact and synaptic activity respectively, with distinct roles in astrocytic function; interestingly, many of these genes are dysregulated in neurodegeneration.

    • Philip Hasel
    • , Owen Dando
    •  & Giles E. Hardingham

  • Article
    | Open Access

    The RNA binding protein FUS functions in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Here the authors show that FUS controls back-splicing reactions leading to circular RNA (circRNA) production in stem cell-derived motor neurons and that ALS-associated FUS mutations affect the biogenesis of circRNAs.

    • Lorenzo Errichelli
    • , Stefano Dini Modigliani
    •  & Irene Bozzoni

  • Article
    | Open Access

    Batrachochytrium dendrobatidis and B. salamandrivoransare both important pathogens of amphibians, but they differ in their host ranges, infection strategies, and host immune responses. Here, Farrer and colleagues compare their genomes and transcriptomes to identify the genetic basis of these differences.

    • Rhys A. Farrer
    • , An Martel
    •  & Christina A. Cuomo

  • Article
    | Open Access

    The phosphorylation of serine/arginine-rich proteins by CDC-like kinase is a central regulatory mechanism for RNA splicing reactions. Here, the authors synthesize a novel small molecule CLK inhibitor and map CLK-responsive alternative splicing events and discover an effect on conjoined gene transcription.

    • Tyler Funnell
    • , Shinya Tasaki
    •  & Samuel Aparicio

  • Article
    | Open Access

    Single-cell gene expression analysis is challenging. This work describes a new droplet-based single cell RNA-seq platform capable of processing tens of thousands of cells across 8 independent samples in minutes, and demonstrates cellular subtypes and host–donor chimerism in transplant patients.

    • Grace X. Y. Zheng
    • , Jessica M. Terry
    •  & Jason H. Bielas

  • Article
    | Open Access

    Bacteria may respond to a change in environment by using alternative transcriptional start sites. Here, the authors use a novel genome-wide capture and reverse transcription method to find substrate-specific start sites for hundreds of genes at single base resolution inClostridium phytofermentans.

    • Magali Boutard
    • , Laurence Ettwiller
    •  & Andrew C. Tolonen

  • Article
    | Open Access

    Salamanders are unique among extant tetrapods for their ability to completely regenerate their limbs. Here, Nogueira and colleagues show that lungfishes, the sister clade of tetrapods, regenerate their fins using analogous gene regulatory changes and morphological steps.

    • Acacio F. Nogueira
    • , Carinne M. Costa
    •  & Igor Schneider

  • Article
    | Open Access

    Recent studies using in depth DNA sequencing techniques led to the identification of cancer driver genes but mainly focused on the effect on their expression. Here, the authors analyse 266 cases of breast cancer and report gene expression signatures associated with the number and character of signature mutations.

    • Marcel Smid
    • , F. Germán Rodríguez-González
    •  & John W. M. Martens

  • Article
    | Open Access

    Long non-coding RNAs are increasingly recognised to be important factors in regulating cellular processes and comprise a large faction of the transcriptome, however most are uncharacterised. Here the authors present RACE-Seq, a tool to improve and extend the annotation of low-expression transcripts.

    • Julien Lagarde
    • , Barbara Uszczynska-Ratajczak
    •  & Jennifer Harrow

  • Article
    | Open Access

    Laser capture microscopy (LCM) coupled with global transcriptome profiling requires relatively large numbers of cells. Here, the authors show that LCM coupled with full-length mRNA-sequencing (LCM-seq) can sequence single cells, and that LCM-seq can provide biological insight on highly similar neuronal populations.

    • Susanne Nichterwitz
    • , Geng Chen
    •  & Eva Hedlund

  • Article
    | Open Access

    Alternative splicing and alternative polyadenylation (APA) contribute to mRNA diversity but are difficult to assess using short read RNA-seq data. Here, the authors use single molecule long-read isoform sequencing and develop a computational pipeline to identify full-length splice isoforms and APA sites in sorghum.

    • Salah E. Abdel-Ghany
    • , Michael Hamilton
    •  & Anireddy S. N. Reddy

  • Article
    | Open Access

    Zea mays is an important crop species and genetic model but uncertainties remain regarding the structure of the transcriptome. Here Wang et al. use single-molecule sequencing and size-fractionated libraries to identify novel transcripts and isoforms illustrating the complexity of maize mRNA.

    • Bo Wang
    • , Elizabeth Tseng
    •  & Doreen Ware

  • Article
    | Open Access

    Rheumatoid arthritis is an inflammatory disease that selectively affects different joints. Here the authors show that gene expression and DNA methylation patterns of fibroblast-like synoviocytes differ between hip and knee joints in patients with RA, thus providing epigenetic and transcriptomic evidence for this anatomic selectivity of inflammation.

    • Rizi Ai
    • , Deepa Hammaker
    •  & Wei Wang

  • Article
    | Open Access

    Colletotrichum tofieldiae is a beneficial root endophyte, whereas the closely related C. incanumis pathogenic. Here the authors compare the genomes and transcriptomes during host plant interaction and demonstrate that the host plant can respond differently to the beneficial endophyte according to phosphate status.

    • Stéphane Hacquard
    • , Barbara Kracher
    •  & Richard J. O’Connell

  • Article
    | Open Access

    Phenotypic and genetic intra-tumor heterogeneity have an important role in cancer progression and therapeutic resistance. Here, the authors show that phenotypically variable tumor subpopulations exhibit higher metastatic potential and display enhanced intra-clonal transcriptomic variability, likely promoted by deregulated spliceosome activity.

    • Alexander Nguyen
    • , Mitsukuni Yoshida
    •  & Sohail F. Tavazoie

  • Article
    | Open Access

    RNA interference inadvertently represses off-target transcripts. Here, Lee et al.report that substituting nucleotide in position 6 of the seed region of the small interfering RNAs with abasic spacers can significantly decrease miRNA-like off-target repression while preserving on-target activity.

    • Hye-Sook Lee
    • , Heeyoung Seok
    •  & Sung Wook Chi

  • Article
    | Open Access

    Expression of transcription factors to alter gene regulation can cause substantial changes to expression across a genome. Here the authors ‘rewire’ E. coliand analyse the global transcriptome alterations to identify novel network interactions.

    • Rebecca Baumstark
    • , Sonja Hänzelmann
    •  & Mark Isalan

  • Article
    | Open Access

    Unravelling the molecular basis of hypertension remains a major challenge. Here, the authors identify the transcription factor GATA5 as a novel regulator of blood pressure and potential genetic determinant of human hypertension and describe a unique mouse model for research of salt-sensitive hypertension.

    • Smail Messaoudi
    • , Ying He
    •  & Mona Nemer

  • Article
    | Open Access

    The burying beetle shows flexible parenting behaviour. Here, the authors show that offspring fare equally well regardless of the sex or number of parents present and find similar gene expression profiles in uniparental and biparental females and in uniparental males, which suggests no specialization in parenting.

    • Darren J. Parker
    • , Christopher B. Cunningham
    •  & Allen J. Moore

  • Article
    | Open Access

    Anaplastic oligodendrogliomas are rare and incurable primary brain tumours with few treatment options. Here Labrecheet al. perform whole-exome sequencing and identify recurring mutations in transcription factor TCF12, which are associated with aggressive tumours.

    • Karim Labreche
    • , Iva Simeonova
    •  & Michel Wager

  • Article
    | Open Access

    The evolutionarily conserved MTREC complex promotes degradation of meiotic mRNAs and regulatory ncRNAs. Here the authors show that MTREC also targets cryptic unstable transcripts and unspliced pre-mRNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process.

    • Yang Zhou
    • , Jianguo Zhu
    •  & Tamás Fischer

  • Article
    | Open Access

    The key regulators that allow transition from proliferative to invasive phenotype in melanoma cells have not been identified yet. The authors perform chromatin and transcriptome profiling followed by comprehensive bioinformatics analysis identifying new candidate regulators for two distinct cell states of melanoma.

    • Annelien Verfaillie
    • , Hana Imrichova
    •  & Stein Aerts

  • Article |

    Basal-like breast cancer is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. Here the authors provide evidence that ID4 is a key controller of mammary stem/progenitor cell self-renewal, acting upstream of Notch signalling to repress luminal fate commitment.

    • Simon Junankar
    • , Laura A. Baker
    •  & Alexander Swarbrick

  • Article |

    In mammals there are two Musashi proteins, MSI1 and MSI2, orthologues of the Drosophila protein, with roles in asymmetric stem cell division and cell fate determination. Here the authors report new functions for MSI2 in colorectal cancer using in vitro loss of function and in vivoectopic overexpression.

    • Shan Wang
    • , Ning Li
    •  & Christopher J. Lengner

  • Article
    | Open Access

    Copy number variation is an important source of genetic variation in natural populations and may have a role in human disease. Here, the authors identify high-order amplification structures that form large extended chromosomes and suggest that these may occur due to accidental template switching in stress conditions.

    • Agnès Thierry
    • , Varun Khanna
    •  & Bernard Dujon

  • Article |

    Strand-specific RNA-seq (ssRNA-seq) data often lack information on 5′ and 3′ ends of transcripts. Here the authors present a novel method for ssRNA-seq that enables the simultaneous profiling of gene expression, TSSs and polyadenylation sites at near-base resolution with a single library.

    • Saurabh Agarwal
    • , Todd S. Macfarlan
    •  & Shigeki Iwase

  • Article |

    Body plan complexity is associated with the number of different cell types, yet the processes that create this diversity are unclear. Here the authors use transcriptomics to test the hypothesis that unlike cancer cells, novel normal cell types arise through sub-specialization of an ancestral cell type.

    • Cong Liang
    • , Alistair R.R. Forrest
    •  & Günter P. Wagner

  • Article
    | Open Access

    The analysis of mammalian transcriptomes could provide new insights into human biology. Here the authors carry out RNA sequencing in a large collection of mouse tissues and compare these data to human transcriptome profiles, identifying a set of constrained genes that carry out basic cellular functions with remarkably constant expression levels across tissues and species.

    • Dmitri D. Pervouchine
    • , Sarah Djebali
    •  & Thomas R. Gingeras

  • Article
    | Open Access

    Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. In this study, the authors use RNA sequencing analyses to characterize differences in the transcriptome between autistic and typically developing brains.

    • Simone Gupta
    • , Shannon E. Ellis
    •  & Dan E. Arking

  • Article |

    microRNAs are short non-coding RNAs that post-transcriptionally regulate gene expression for which the identification of promoter and primary transcripts (pri-miRNAs) has been difficult. Here the authors describe microTSS, an algorithm that supports the precise identification of intergenic pri-miRNA transcription start sites.

    • Georgios Georgakilas
    • , Ioannis S. Vlachos
    •  & Artemis G. Hatzigeorgiou

  • Article |

    Molecular and functional differences between induced pluripotent stem cells (iPSCs) derived from distinct cell types have been described. Here the authors show, by comparing human iPSCs derived from fibroblasts or cord blood, that the competence in activating developmental genes upon differentiation is influenced by the donor cell of origin.

    • Jong-Hee Lee
    • , Jung Bok Lee
    •  & Mickie Bhatia

  • Article |

    The blind mole rat (BMR), Spalax galili, is perfectly adapted to life underground. Here, the authors sequence the BMR genome and transcriptome and highlight genomic features that may have played a role in adaptation to extreme underground stressors, such as darkness hypercapnia and hypoxia.

    • Xiaodong Fang
    • , Eviatar Nevo
    •  & Jun Wang

  • Article
    | Open Access

    Gene expression is highly variable between tissues, and changes during development and with age. Here, the authors provide a comprehensive RNA-Seq analysis of the rat transcriptome, spanning eleven organs, four developmental stages and both sexes.

    • Ying Yu
    • , James C. Fuscoe
    •  & Charles Wang

  • Article
    | Open Access

    Tumour biopsies contain contaminating normal cells and these can influence the analysis of tumour samples. In this study, Yoshihara et al.develop an algorithm based on gene expression profiles from The Cancer Genome Atlas to estimate the number of contaminating normal cells in tumour samples.

    • Kosuke Yoshihara
    • , Maria Shahmoradgoli
    •  & Roel G.W. Verhaak

  • Article
    | Open Access

    Viruses contribute to the pathogenesis of certain cancers. Using massively parallel sequencing data from The Cancer Genome Atlas to analyse viral expression in 19 tumour types, Tang et al. both confirm and reject previously described viral associations and present new information on viral integration and host interaction.

    • Ka-Wei Tang
    • , Babak Alaei-Mahabadi
    •  & Erik Larsson

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