DNA sequencing

  • Article
    | Open Access

    The Lake Malawi cichlid fishes are an example of extreme vertebrate radiation; however, there is very little sequence divergence among the species. Here the authors present a comparative genome-wide methylome study to suggest DNA methylation played a major role in the extensive phenotypic diversity amongst these fishes.

    • Grégoire Vernaz
    • , Milan Malinsky
    •  & Eric A. Miska
  • Article
    | Open Access

    Despite being a common congenital facial anomaly, the genetic etiology of craniofacial microsomia (CFM) is not well understood. Here, the authors use exome and genome sequencing of 146 individuals with CFM to identify haploinsufficient variants in SF3B2 as a prevalent underlying cause.

    • Andrew T. Timberlake
    • , Casey Griffin
    •  & Daniela V. Luquetti
  • Article
    | Open Access

    Mobile element insertions (MEIs) are a source of repetitive genetic variation and can lead to genetic disorders. Here the authors use Cas9-targeted nanopore sequencing to efficiently saturate enrichment for known and non-reference MEIs.

    • Torrin L. McDonald
    • , Weichen Zhou
    •  & Alan P. Boyle
  • Article
    | Open Access

    Several existing algorithms predict the methylation of DNA using Nanopore sequencing signals, but it is unclear how they compare in performance. Here, the authors benchmark the performance of several such tools, and propose METEORE, a consensus tool that improves prediction accuracy.

    • Zaka Wing-Sze Yuen
    • , Akanksha Srivastava
    •  & Eduardo Eyras
  • Article
    | Open Access

    Sequencing and mapping of long repetitive regions can be challenging due to technical difficulties in sequencing and assembly of the sequence data. Here authors report the complete sequences of subtelomeric homologous (SH) regions of the fission yeast Schizosaccharomyces pombe to reveal highly polymorphic and hot spots for genome variation features.

    • Yusuke Oizumi
    • , Takuto Kaji
    •  & Junko Kanoh
  • Article
    | Open Access

    The detection of aberrations in circulating tumour DNA represents a non-invasive method to survey the oncogenes and tumour suppressors that are modified within a patient’s cancer. Here, the authors analysed more than 10,000 patients using a targeted sequencing panel and report on the frequencies of the mutations that they found.

    • Yongliang Zhang
    • , Yu Yao
    •  & Qiang Zeng
  • Article
    | Open Access

    Working with cancer genomes from multiple projects can increase investigative power, but quality of sequences can vary. Here, the authors present a framework for comparing whole genome sequencing quality to help researchers guide downstream analyses and exclude poor quality samples.

    • Justin P. Whalley
    • , Ivo Buchhalter
    •  & Ivo G. Gut
  • Article
    | Open Access

    The molecular basis of the clinically important MAM blood group antigen present in most humans is unknown. We identify EMP3 as its encoding gene, establishing MAM as a new blood group system, and demonstrate the role of EMP3 in erythropoiesis through its interaction with the signalling molecule CD44.

    • Nicole Thornton
    • , Vanja Karamatic Crew
    •  & David J. Anstee
  • Article
    | Open Access

    DNA is an attractive digital data storing medium due to high information density and longevity. Here the authors use millions of sequences to investigate inherent biases in DNA synthesis and PCR amplification.

    • Yuan-Jyue Chen
    • , Christopher N. Takahashi
    •  & Karin Strauss
  • Article
    | Open Access

    Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

    • Lide Han
    • , Xuefang Zhao
    •  & Douglas M. Ruderfer
  • Article
    | Open Access

    The complexity of structural variation (SV) and short tandem repeats (STRs) makes it necessary to apply different calling and filtering strategies to sequencing datasets. Here, Jakubosky et al. report a comprehensive SV and STR callset from whole-genome sequencing of 477 individuals from iPSCORE and HipSci using five algorithms.

    • David Jakubosky
    • , Erin N. Smith
    •  & Kelly A. Frazer
  • Article
    | Open Access

    Most human protein-coding genes are expressed as multiple isoforms. Here the authors present ORF Capture-seq that uses cloned ORFs as probes to capture and sequence full length transcript sequences. This enables highly sensitive characterization of eukaryotic transcriptomes.

    • Gloria M. Sheynkman
    • , Katharine S. Tuttle
    •  & Marc Vidal
  • Article
    | Open Access

    Common variants identified by large-scale genomewide association studies cannot account fully account for the heritability of schizophrenia (SCZ). Here, the authors report high-coverage whole-genome sequencing of 1162 SCZ cases and 936 controls and explore the contribution of different types of variants to SCZ.

    • Matthew Halvorsen
    • , Ruth Huh
    •  & Jin P. Szatkiewicz
  • Article
    | Open Access

    Non-canonical HLA-bound peptides from presumed non-coding regions are potential targets for cancer immunotherapy, but their discovery remains challenging. Here, the authors integrate exome sequencing, transcriptomics, ribosome profiling, and immunopeptidomics to identify tumor-specific non-canonical HLA-bound peptides.

    • Chloe Chong
    • , Markus Müller
    •  & Michal Bassani-Sternberg
  • Article
    | Open Access

    Little is known about the genetics of sclerosing stromal tumor of the ovary, a rare type of sex cord-stromal tumor. Here, the authors use sequencing strategies to show that in a cohort of 26 tumor samples 65% carry a FHL2-GLI2 fusion gene and demonstrate in vitro that the fusion gene has oncogenic properties.

    • Sarah H. Kim
    • , Arnaud Da Cruz Paula
    •  & Britta Weigelt
  • Article
    | Open Access

    Birch pitch is thought to have been used in prehistoric times as hafting material or antiseptic and tooth imprints suggest that it was chewed. Here, the authors report a 5,700 year-old piece of chewed birch pitch from Denmark from which they successfully recovered a complete ancient human genome and oral microbiome DNA.

    • Theis Z. T. Jensen
    • , Jonas Niemann
    •  & Hannes Schroeder
  • Article
    | Open Access

    Haplotype information inferred by phasing is useful in genetic and genomic analysis. Here, the authors develop SHAPEIT4, a phasing method that exhibits sub-linear running time, provides accurate haplotypes and enables integration of external phasing information.

    • Olivier Delaneau
    • , Jean-François Zagury
    •  & Emmanouil T. Dermitzakis
  • Article
    | Open Access

    Structural variants may be omitted in sequence analysis despite their importance in genome variation and phenotypic impact. Here the authors present GraphTyper2, which uses pangenome graphs to genotype structural variants using short-reads and can be applied in large-scale sequencing studies.

    • Hannes P. Eggertsson
    • , Snaedis Kristmundsdottir
    •  & Pall Melsted
  • 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

    Despite the importance of grapevine cultivation in human history and the economic values of cultivar improvement, large-scale genomic variation data are lacking. Here the authors resequence 472 Vitis accessions and use the identified genetic variations for domestication history, demography, and GWAS analyses.

    • Zhenchang Liang
    • , Shengchang Duan
    •  & Yang Dong
  • Article
    | Open Access

    Adenine base editors are an important contribution to the genome editing toolbox. Here the authors present EndoV-seq, an endonuclease-based assay for evaluating genomewide off-target effects of base editing.

    • Puping Liang
    • , Xiaowei Xie
    •  & Zhou Songyang
  • Article
    | Open Access

    Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

    • Chongyuan Luo
    • , Angeline Rivkin
    •  & Joseph R. Ecker
  • Article
    | Open Access

    Long-read sequencing technologies facilitate efficient and high quality genome assembly. Here Michael et al. achieve a fast reference assembly for Arabidopsis thaliana KBS-Mac-74 accession using the handheld Oxford Nanopore MinION sequencer and consumer computing hardware, and demonstrate its usefulness in resolving complex structural variation.

    • Todd P. Michael
    • , Florian Jupe
    •  & Joseph R. Ecker
  • Article
    | Open Access

    Selaginella lepidophylla is a clubmoss with extreme desiccation tolerance. Here, the authors assemble its highly heterozygotic haplotypes and examine gene expression changes during desiccation, which shed light on the mechanisms for maintaining a small genome size and adaptation to extreme drying.

    • Robert VanBuren
    • , Ching Man Wai
    •  & Todd P. Michael
  • Article
    | Open Access

    Haplotype information is important in investigating many biological phenomena. Here, Porubsky et al. combine Strand-seq with long-read or linked-read sequencing to obtain complete and genome-wide haplotypes of a single individual genome at manageable costs.

    • David Porubsky
    • , Shilpa Garg
    •  & Tobias Marschall
  • Article
    | Open Access

    Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

    • Coen M. Adema
    • , LaDeana W. Hillier
    •  & Richard K. Wilson
  • Article
    | Open Access

    The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.

    • Rasika Ann Mathias
    • , Margaret A. Taub
    •  & Kathleen C. Barnes
  • Article
    | Open Access

    The ability to accurately sequence long DNA molecules is important across biology. Here, Lan et al. report a droplet-based method that barcodes single DNA molecules, allowing the full-length molecules to be sequenced with multi-fold coverage using short-read next-generation sequencing.

    • Freeman Lan
    • , John R. Haliburton
    •  & Adam R. Abate
  • Article
    | Open Access

    DNA N6-methyladenine is prevalent in prokaryotes, and is recently also detected in eukaryotes such as roundworm and fly. Here, Luo et al. report a DpnI-assisted base resolution method that detects 6mA genome-wide with nanograms of input DNA and lower sequencing depth than the previous restriction enzyme-based approach.

    • Guan-Zheng Luo
    • , Fang Wang
    •  & Chuan He
  • Article
    | Open Access

    Read mapping and alignment tools are critical for many applications based on MinION sequencers. Here, the authors present GraphMap, a mapping algorithm designed to analyze nanopore sequencing reads, that progressively refines candidate alignments to handle potentially high error rates to align long reads.

    • Ivan Sović
    • , Mile Šikić
    •  & Niranjan Nagarajan
  • Article
    | Open Access

    Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

    • Tyler S. Alioto
    • , Ivo Buchhalter
    •  & Ivo G. Gut