Genomic analysis

  • Article
    | Open Access

    Current high-throughput single-cell transcriptomic methods are incompatible with paraformaldehyde, a common cell fixation technique. Here the authors present FD-seq, a method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single cells.

    • Hoang Van Phan
    • , Michiel van Gent
    •  & Savaş Tay
  • Article
    | Open Access

    STAT1a is required for pro-inflammatory responses in macrophages. Here the authors reveal that post-translational modification of STAT1a, ADPribosylation, plays a critical role in enhancer formation and activation, thus modulating IFNγ-stimulated inflammatory responses in macrophages.

    • Rebecca Gupte
    • , Tulip Nandu
    •  & W. Lee Kraus
  • Article
    | Open Access

    Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.

    • Karoline Holler
    • , Anika Neuschulz
    •  & Jan Philipp Junker
  • Article
    | Open Access

    Circulating tumour DNA (ctDNA) represents a non-invasive option to monitor cancer progression. Here, the authors perform deep sequencing of plasma cell-free DNA, and find that nucleosome-dependent cfDNA degradation at 6 specific regulatory regions is predictive of ctDNA burden.

    • Guanhua Zhu
    • , Yu A. Guo
    •  & Anders J. Skanderup
  • Article
    | Open Access

    Glucocorticoid receptors (GR) are thought to bind DNA as dimers or monomers, to regulate different transcription pathways. Here, the authors perform genome-wide studies on GRs with mutations that impair dimerization and provide evidence that monomeric GRs do not play a significant physiologic role.

    • Thomas A. Johnson
    • , Ville Paakinaho
    •  & Diego M. Presman
  • Article
    | Open Access

    Short read RNA sequencing and DNA sequence contain useful information for profiling polyadenylation sites, but each also possesses inherent limitations when examined independently. Aptardi combines these data and significantly improves annotation of polyadenylation sites in the expressed transcriptome.

    • Ryan Lusk
    • , Evan Stene
    •  & Laura M. Saba
  • Article
    | Open Access

    Malignant rhabdoid tumours (MRT) have been suggested to originate in the ectoderm-derived neural crest. Here, the authors analyse MRTs using phylogenetics, scRNA-seq, and patient-derived organoids; they find evidence for an MRT origin in the neural crest lineage and suggest differentiation treatment with HDAC/mTOR inhibitors.

    • Lars Custers
    • , Eleonora Khabirova
    •  & Jarno Drost
  • Article
    | Open Access

    Telomeres can be maintained by a telomerase-independent mechanism called an alternative lengthening of telomeres (ALT). Here the authors use mouse Terc (telomerase RNA) knockout embryonic cells and provide longitudinal analysis of ALT telomeres maintained with non-telomeric sequences.

    • Chuna Kim
    • , Sanghyun Sung
    •  & Junho Lee
  • Article
    | Open Access

    Genomic aberrations disrupting chromosome spatial domains can lead to disease. Here, the authors investigate the impact of DNA damage response and repair on 3D genome folding, comparing wild type cells and ataxia telangiectasia mutated patient cells, and characterise both cell type-specific and shared changes to genome organization during the response to damage.

    • Jacob T. Sanders
    • , Trevor F. Freeman
    •  & Rachel Patton McCord
  • Article
    | Open Access

    Genome-wide maps of evolutionary constraint and large-scale compendia of epigenomic and transcription factor data provide complementary information for genome annotation. Here, the authors develop the Constrained Non-Exonic Predictor (CNEP) that enables better understanding of their relationship.

    • Olivera Grujic
    • , Tanya N. Phung
    •  & Jason Ernst
  • Article
    | Open Access

    Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.

    • Yubo Liu
    • , Qiushi Chen
    •  & Jianing Zhang
  • Article
    | Open Access

    Neuronal differentiation requires rearrangement of the transcriptional and chromatin landscapes of neural cells. Here, the authors study in-vitro neuronal differentiation of murine embryonic stem cells (ESCs) to show that this process is modulated by DOT1L activity, which regulates H3K79me2 accumulation, and preserves accessibility of SOX2-bound enhancers.

    • Francesco Ferrari
    • , Laura Arrigoni
    •  & Thomas Manke
  • Article
    | Open Access

    The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide.

    • Christopher H. Douse
    • , Iva A. Tchasovnikarova
    •  & Yorgo Modis
  • Article
    | Open Access

    With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

    • Matthew H. Bailey
    • , William U. Meyerson
    •  & Christian von Mering
  • Article
    | Open Access

    Droplet-based high throughput single cell sequencing techniques can often lose information on transcript splicing and heterogenity. Here the authors introduce ScNaUmi-seq, which uses Oxford Nanopore sequencing and barcoding to generate high accuracy full length sequences.

    • Kevin Lebrigand
    • , Virginie Magnone
    •  & Rainer Waldmann
  • Article
    | Open Access

    Early life exposure to environmental stressors, including endocrine disrupting chemicals (EDCs), can impact health later in life. Here, the authors show that neonatal EDC exposure in rats causes epigenetic reprogramming in the liver, which is transcriptionally silent until animals are placed on a Western-style diet.

    • Lindsey S. Treviño
    • , Jianrong Dong
    •  & Cheryl Lyn Walker
  • Article
    | Open Access

    The initial mutational processes and how these lead to progression in multiple myeloma (MM) are unclear. Here, the authors identify mutational signatures that occur over time in a large cohort of MM patients and suggest features that may help in early diagnosis.

    • Even H. Rustad
    • , Venkata Yellapantula
    •  & Francesco Maura
  • Article
    | Open Access

    Prior to genome assembly, the raw sequencing reads must be analyzed for assessment of major genome characteristics such as genome size, heterozygosity, and repetitiveness. For this purpose, the authors introduce GenomeScope 2.0, an extension of GenomeScope for polyploid genomes, and Smudgeplot, which can estimate a genome’s ploidy.

    • T. Rhyker Ranallo-Benavidez
    • , Kamil S. Jaron
    •  & Michael C. Schatz
  • Article
    | Open Access

    Epstein-Barr virus (EBV) episomes tether to the host chromosome via EBNA1. Here, using circular chromosome conformation capture (4C), Kim et al. identify attachment sites and show that EBV episomes preferentially associate with transcriptionally silenced genes in Burkitt lymphoma cells.

    • Kyoung-Dong Kim
    • , Hideki Tanizawa
    •  & Paul M. Lieberman
  • Article
    | Open Access

    Single strand breaks represent the most common form of DNA damage yet no methods to map them in a genome-wide fashion at single nucleotide resolution exist. Here the authors develop such a method and apply to uncover patterns of single-strand DNA “breakome” in different biological conditions.

    • Huifen Cao
    • , Lorena Salazar-García
    •  & Philipp Kapranov
  • Article
    | Open Access

    Meiotic crossovers (COs) generate genetic variation and ensure proper chromosome segregation. Here, the authors develop a method for identifying COs at kilobase resolution in pooled recombinants using linked-read sequencing data, and apply it to investigate genome-wide CO landscapes of Arabidopsis thaliana.

    • Hequan Sun
    • , Beth A. Rowan
    •  & Korbinian Schneeberger
  • Article
    | Open Access

    Meiotic DSB formation, repair and recombination occur in a continuum of substages termed leptonema, zygonema, pachynema, and diplonema. Here, authors develop a method for isolating pure sub-populations of nuclei that allows for detailed study of meiotic substages.

    • Kwan-Wood Gabriel Lam
    • , Kevin Brick
    •  & R. Daniel Camerini-Otero
  • Article
    | Open Access

    Squamous cell lung cancer has dismal prognosis due to the dearth of effective treatments. Here, the authors perform an integrated proteogenomic analysis of the disease, revealing three proteomics-based subtypes and suggesting potential therapeutic opportunities.

    • Paul A. Stewart
    • , Eric A. Welsh
    •  & Eric B. Haura
  • Article
    | Open Access

    Sequencing of newly synthesised RNA can reveal the transcriptional dynamics in a population of cells. Here the authors develop NASC-seq to bring this sensitivity and temporal resolution to single-cell analysis.

    • Gert-Jan Hendriks
    • , Lisa A. Jung
    •  & Rickard Sandberg
  • Article
    | Open Access

    Meiotic crossover (CO) landscape differs inter- and intra-species, as well as between sexes. Here, the authors show that male meiosis produces more COs than female in maize and detect CO maturation inefficiency in some genetic backgrounds, which may help to improve breeding efficiency.

    • Cheng Luo
    • , Xiang Li
    •  & Jianbing Yan
  • Article
    | Open Access

    Due to various structural and sequence complexities, the human Y chromosome is challenging to sequence and characterize. Here, the authors develop a strategy to sequence native, unamplified flow sorted Y chromosomes with a nanopore sequencing platform, and report the first assembly of a human Y chromosome of African origin.

    • Lukas F. K. Kuderna
    • , Esther Lizano
    •  & Tomas Marques-Bonet
  • Article
    | Open Access

    Natural hair colour in Europeans is a complex genetic trait. Here, the authors carry out a genome-wide association study using UK BioBank data, suggesting that in combination with pigmentation genes, variants with roles in hair texture and growth can affect hair colouration or our perception of it.

    • Michael D. Morgan
    • , Erola Pairo-Castineira
    •  & Ian J. Jackson
  • Article
    | Open Access

    In vivo existence of guanine-rich four-stranded RNA structures (G4-RNAs) has been a matter of debate. Here the authors developed a protocol, G4RP-seq, to capture and identify transcriptome-wide G4-RNA, providing insights into the formation of transient G4-RNA in live human cells.

    • Sunny Y. Yang
    • , Pauline Lejault
    •  & David Monchaud
  • Article
    | Open Access

    Algorithms designed to find rare cells in single cell RNA-seq data sets cannot cope with data sets containing tens of thousands of cells. Here the authors present Finder of Rare Entities (FiRE), an algorithm that uses the Sketching technique to assign a rareness score to every expression profile in large RNA-seq data sets.

    • Aashi Jindal
    • , Prashant Gupta
    •  & Debarka Sengupta
  • Article
    | Open Access

    Termination of RNA polymerase II (RNAPII) transcription is an essential step of gene expression. Here the authors provide evidence that in fission yeast termination of ncRNA genes occurs by a cleavage-dependent mechanism involving recruitment of mRNA 3′ end processing factors and requires the conserved Ysh1/CPSF-73 and Dhp1/XRN2 nucleases.

    • Marc Larochelle
    • , Marc-Antoine Robert
    •  & François Bachand
  • Article
    | Open Access

    In Drosophila the Male-Specific Lethal complex (MSLc) mediates upregulation of the single male X chromosome. Here the authors provide evidence that MSL2 also targets autosomal genes required for proper development and that MSL2 binds and similarly regulates mouse orthologues.

    • Claudia Isabelle Keller Valsecchi
    • , M. Felicia Basilicata
    •  & Asifa Akhtar
  • Article
    | Open Access

    Japonica rice can grow further north than wild or indica rice and is more tolerant of cold climates. Here, the authors show that bZIP73 likely underwent selection in the early phase of rice domestication to facilitate cold tolerance in japonica by modulating ABA and ROS homeostasis.

    • Citao Liu
    • , Shujun Ou
    •  & Chengcai Chu
  • Article
    | Open Access

    Single-cell RNA-barcoding and sequencing is an efficient, genome-wide method to characterize cellular identities. Here the authors systematically evaluate the protocol and develop molecular crowding SCRB-seq with improved sensitivity and cost-efficiency.

    • Johannes W. Bagnoli
    • , Christoph Ziegenhain
    •  & Wolfgang Enard
  • Article
    | Open Access

    The UK Biobank provides data for three depression-related phenotypes. Here, Howard et al. perform a genome-association study for broad depression, probable major depressive disorder (MDD) and hospital record-coded MDD in up to 322,580 UK Biobank participants which highlights excitatory synaptic pathways.

    • David M. Howard
    • , Mark J. Adams
    •  & Andrew M. McIntosh
  • Article
    | Open Access

    Physical mapping of DNA can be used to detect structural variants and for whole-genome haplotype assembly. Here, the authors use CRISPR-Cas9 and high-speed atomic force microscopy to ‘nanomap’ single molecules of DNA.

    • Andrey Mikheikin
    • , Anita Olsen
    •  & Jason Reed
  • Article
    | Open Access

    Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.

    • Ramunas Stepanauskas
    • , Elizabeth A. Fergusson
    •  & Arvydas Lubys
  • Article
    | Open Access

    Viruses play an important role in microbial communities but, due to limitations of available techniques, our understanding of viral diversity is limited. Here, the authors use SVGs and identify highly abundant viruses in marine communities that have been previously overlooked.

    • Francisco Martinez-Hernandez
    • , Oscar Fornas
    •  & Manuel Martinez-Garcia