Sequencing

  • Article
    | Open Access

    Circulating cell-free mRNA holds great promise as a non-invasive diagnostic biomarker. Here the authors show that cell-free mRNA captures transcripts from the bone marrow and can be used to non-invasively monitor dynamic changes in bone marrow physiology.

    • Arkaitz Ibarra
    • , Jiali Zhuang
    • , Yue Zhao
    • , Neeraj S. Salathia
    • , Vera Huang
    • , Alexander D. Acosta
    • , Jonathan Aballi
    • , Shusuke Toden
    • , Amy P. Karns
    • , Intan Purnajo
    • , Julianna R. Parks
    • , Lucy Guo
    • , James Mason
    • , Darren Sigal
    • , Tina S. Nova
    • , Stephen R. Quake
    •  & Michael Nerenberg
  • Article
    | Open Access

    Mutational signatures induced by ionising radiation remain largely unexplored. Here in TP53 mutant mice, the authors characterise the genomic landscape of tumours induced by high- and low-energy radiation.

    • Yun Rose Li
    • , Kyle D. Halliwill
    • , Cassandra J. Adams
    • , Vivek Iyer
    • , Laura Riva
    • , Rashid Mamunur
    • , Kuang-Yu Jen
    • , Reyno del Rosario
    • , Erik Fredlund
    • , Gillian Hirst
    • , Ludmil B. Alexandrov
    • , David Adams
    •  & Allan Balmain
  • Article
    | Open Access

    Mikania micrantha is an extremely fast-growing invasive plant species that can cause serious damage to natural ecosystems. Here, the authors assemble its chromosome-scale reference genome and explore possible mechanisms that contribute to its rapid growth.

    • Bo Liu
    • , Jian Yan
    • , Weihua Li
    • , Lijuan Yin
    • , Ping Li
    • , Hanxia Yu
    • , Longsheng Xing
    • , Minling Cai
    • , Hengchao Wang
    • , Mengxin Zhao
    • , Jin Zheng
    • , Feng Sun
    • , Zhenzhen Wang
    • , Zhaoyang Jiang
    • , Qiaojing Ou
    • , Shubin Li
    • , Lu Qu
    • , Qilei Zhang
    • , Yaping Zheng
    • , Xi Qiao
    • , Yu Xi
    • , Yan Zhang
    • , Fan Jiang
    • , Cong Huang
    • , Conghui Liu
    • , Yuwei Ren
    • , Sen Wang
    • , Hangwei Liu
    • , Jianyang Guo
    • , Haihong Wang
    • , Hui Dong
    • , Changlian Peng
    • , Wanqiang Qian
    • , Wei Fan
    •  & Fanghao Wan
  • Article
    | Open Access

    RNA-sequencing is mostly used to assess gene expression; however, it can also give information about genetic variants. Here, the authors present CaSpER, a statistical framework that utilises RNA-sequencing reads to identify and visualise CNV events by integrating transcriptome-wide expression and allelic shift profiles.

    • Akdes Serin Harmanci
    • , Arif O. Harmanci
    •  & Xiaobo Zhou
  • 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
    • , Thais Basili
    • , Higinio Dopeso
    • , Rui Bi
    • , Fresia Pareja
    • , Edaise M. da Silva
    • , Rodrigo Gularte-Mérida
    • , Zhen Sun
    • , Sho Fujisawa
    • , Caitlin G. Smith
    • , Lorenzo Ferrando
    • , Ana Paula Martins Sebastião
    • , Yonina Bykov
    • , Anqi Li
    • , Catarina Silveira
    • , Charles W. Ashley
    • , Anthe Stylianou
    • , Pier Selenica
    • , Wesley R. Samore
    • , Achim A. Jungbluth
    • , Dmitriy Zamarin
    • , Nadeem R. Abu-Rustum
    • , Kristian Helin
    • , Robert A. Soslow
    • , Jorge S. Reis-Filho
    • , Esther Oliva
    •  & 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
    • , Katrine Højholt Iversen
    • , Anna K. Fotakis
    • , Shyam Gopalakrishnan
    • , Åshild J. Vågene
    • , Mikkel Winther Pedersen
    • , Mikkel-Holger S. Sinding
    • , Martin R. Ellegaard
    • , Morten E. Allentoft
    • , Liam T. Lanigan
    • , Alberto J. Taurozzi
    • , Sofie Holtsmark Nielsen
    • , Michael W. Dee
    • , Martin N. Mortensen
    • , Mads C. Christensen
    • , Søren A. Sørensen
    • , Matthew J. Collins
    • , M. Thomas P. Gilbert
    • , Martin Sikora
    • , Simon Rasmussen
    •  & Hannes Schroeder
  • Article
    | Open Access

    The retina is a heterogeneous tissue composed of multiple cell types. Via single-nuclei RNA sequencing on human neural retinal tissue, the authors characterise the transcriptome profile for individual cell types in the human retina.

    • Qingnan Liang
    • , Rachayata Dharmat
    • , Leah Owen
    • , Akbar Shakoor
    • , Yumei Li
    • , Sangbae Kim
    • , Albert Vitale
    • , Ivana Kim
    • , Denise Morgan
    • , Shaoheng Liang
    • , Nathaniel Wu
    • , Ken Chen
    • , Margaret M. DeAngelis
    •  & Rui Chen
  • Article
    | Open Access

    Compared to single nucleotide variants and short indels, structural variants (SVs) are often more challenging to detect using high-throughput sequencing based methods. Here, the authors develop LinkedSV, a computational tool for SV detection using linked-read exome and genome sequencing data.

    • Li Fang
    • , Charlly Kao
    • , Michael V. Gonzalez
    • , Fernanda A. Mafra
    • , Renata Pellegrino da Silva
    • , Mingyao Li
    • , Sören-Sebastian Wenzel
    • , Katharina Wimmer
    • , Hakon Hakonarson
    •  & Kai Wang
  • Article
    | Open Access

    The off-target effects and on-target mutations of CRISPR editing in higher non-human primates are complex. Here the authors perform whole genome trio sequencing of rhesus monkeys and see no unexpected mutations.

    • Xin Luo
    • , Yaoxi He
    • , Chao Zhang
    • , Xiechao He
    • , Lanzhen Yan
    • , Min Li
    • , Ting Hu
    • , Yan Hu
    • , Jin Jiang
    • , Xiaoyu Meng
    • , Weizhi Ji
    • , Xudong Zhao
    • , Ping Zheng
    • , Shuhua Xu
    •  & Bing Su
  • Article
    | Open Access

    t-SNE is widely used for dimensionality reduction and visualization of high-dimensional single-cell data. Here, the authors introduce a protocol to help avoid common shortcomings of t-SNE, for example, enabling preservation of the global structure of the data.

    • Dmitry Kobak
    •  & Philipp Berens
  • 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
    • , Matthew R. Robinson
    • , Jonathan L. Marchini
    •  & 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
    • , Doruk Beyter
    • , Hakon Jonsson
    • , Astros Skuladottir
    • , Marteinn T. Hardarson
    • , Daniel F. Gudbjartsson
    • , Kari Stefansson
    • , Bjarni V. Halldorsson
    •  & Pall Melsted
  • Article
    | Open Access

    The poly(A) tails on mRNA are vital for their function but it is difficult to map full-length sequences of mRNA isoforms with the entire poly(A) tails. Here the authors develop PAIso−seq which can measure isoform specific poly(A) tail length and base composition at single-cell sensitivity.

    • Yusheng Liu
    • , Hu Nie
    • , Hongxiang Liu
    •  & Falong Lu
  • Article
    | Open Access

    C. elegans is a commonly used model organism in the study of ageing, and differences in genetic background can result in varying strain longevity. Here the authors demonstrate that a background mutation in fln-2 affects life-limiting pharyngeal infection and that in the mutant background the beneficial effect of sir-2.1 over-expression is suppressed.

    • Yuan Zhao
    • , Hongyuan Wang
    • , Richard J. Poole
    •  & David Gems
  • Article
    | Open Access

    It is challenging to characterize diverse transcript isoforms by short-read sequencing. Here the authors report full-length transcriptomes in rat hippocampus by hybrid-sequencing, predict isoform-specific translational status, and reconstruct open reading frames validated by mass spectrometry.

    • Xi Wang
    • , Xintian You
    • , Julian D. Langer
    • , Jingyi Hou
    • , Fiona Rupprecht
    • , Irena Vlatkovic
    • , Claudia Quedenau
    • , Georgi Tushev
    • , Irina Epstein
    • , Bernhard Schaefke
    • , Wei Sun
    • , Liang Fang
    • , Guipeng Li
    • , Yuhui Hu
    • , Erin M. Schuman
    •  & Wei Chen
  • Article
    | Open Access

    Genomics DNA library preparation from formalin-fixed paraffin-embedded tissues is challenging. Here the authors describe CUTseq that uses restriction enzymes and in vitro amplification to barcode samples for reduced representation genome sequencing.

    • Xiaolu Zhang
    • , Silvano Garnerone
    • , Michele Simonetti
    • , Luuk Harbers
    • , Marcin Nicoś
    • , Reza Mirzazadeh
    • , Tiziana Venesio
    • , Anna Sapino
    • , Johan Hartman
    • , Caterina Marchiò
    • , Magda Bienko
    •  & Nicola Crosetto
  • Article
    | Open Access

    Large whole-exome sequencing studies have suggested that the genetic architecture of syndromic congenital heart disease (CHD) is different from sporadic forms. Here, Watkins et al. estimate the relative contribution of damaging recessive and de novo genotypes to CHD in 2391 trios and find them to be associated with different gene functions.

    • W. Scott Watkins
    • , E. Javier Hernandez
    • , Sergiusz Wesolowski
    • , Brent W. Bisgrove
    • , Ryan T. Sunderland
    • , Edwin Lin
    • , Gordon Lemmon
    • , Bradley L. Demarest
    • , Thomas A. Miller
    • , Daniel Bernstein
    • , Martina Brueckner
    • , Wendy K. Chung
    • , Bruce D. Gelb
    • , Elizabeth Goldmuntz
    • , Jane W. Newburger
    • , Christine E. Seidman
    • , Yufeng Shen
    • , H. Joseph Yost
    • , Mark Yandell
    •  & Martin Tristani-Firouzi
  • Article
    | Open Access

    Primed adaptation in the CRISPR-Cas system helps recognition of previously encountered sequence elements and promotes the formation of new memories. Here the authors characterized spacer precursors of type I-E and type I-F CRISPR-Cas system using in vivo models.

    • Anna A. Shiriaeva
    • , Ekaterina Savitskaya
    • , Kirill A. Datsenko
    • , Irina O. Vvedenskaya
    • , Iana Fedorova
    • , Natalia Morozova
    • , Anastasia Metlitskaya
    • , Anton Sabantsev
    • , Bryce E. Nickels
    • , Konstantin Severinov
    •  & Ekaterina Semenova
  • Article
    | Open Access

    Synthetic RNA-based devices can dynamically control a wide range of processes. Here the authors develop a quantitative and high-throughput mammalian cell-based RNA-seq assay to efficiently engineer ribozyme switches.

    • Joy S. Xiang
    • , Matias Kaplan
    • , Peter Dykstra
    • , Michaela Hinks
    • , Maureen McKeague
    •  & Christina D. Smolke
  • 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
    • , Pádraic J. Flood
    • , Ronny Brandt
    • , Janina Fuss
    • , Angela M. Hancock
    • , Richard W. Michelmore
    • , Bruno Huettel
    •  & Korbinian Schneeberger
  • Article
    | Open Access

    The benefit of combined CDK4/6 and anti-HER2 therapy in breast cancer is limited due to acquired resistance. Here, the authors perform single-cell analysis and show an immature myeloid cell population to infiltrate resistant tumors, and that combined cabozantinib and checkpoint therapy overcome this resistance with a sustained efficacy.

    • Qingfei Wang
    • , Ian H. Guldner
    • , Samantha M. Golomb
    • , Longhua Sun
    • , Jack A. Harris
    • , Xin Lu
    •  & Siyuan Zhang
  • Article
    | Open Access

    Tuberculosis meningitis (TBM) is a severe form of TB with limited treatment options. Here, the authors perform RNA sequencing on whole blood and on ventricular and lumbar cerebrospinal fluid (CSF) samples from pediatric patients treated for TBM to characterize the immune response and tissue damage.

    • Ursula K. Rohlwink
    • , Anthony Figaji
    • , Katalin A. Wilkinson
    • , Stuart Horswell
    • , Abdul K. Sesay
    • , Armin Deffur
    • , Nico Enslin
    • , Regan Solomons
    • , Ronald Van Toorn
    • , Brian Eley
    • , Michael Levin
    • , Robert J. Wilkinson
    •  & Rachel P. J. Lai
  • Article
    | Open Access

    Pilocytic astrocytoma is a low-grade pediatric glioma, characterized by a single BRAF rearrangement. Here, Reitman and colleagues use single-cell RNA sequencing to reveal molecular hallmarks of the disease that might be targeted therapeutically.

    • Zachary J. Reitman
    • , Brenton R. Paolella
    • , Guillaume Bergthold
    • , Kristine Pelton
    • , Sarah Becker
    • , Robert Jones
    • , Claire E. Sinai
    • , Hayley Malkin
    • , Ying Huang
    • , Leslie Grimmet
    • , Zachary T. Herbert
    • , Yu Sun
    • , Jessica L. Weatherbee
    • , John A. Alberta
    • , John F. Daley
    • , Orit Rozenblatt-Rosen
    • , Alexandra L. Condurat
    • , Kenin Qian
    • , Prasidda Khadka
    • , Rosalind A. Segal
    • , Daphne Haas-Kogan
    • , Mariella G. Filbin
    • , Mario L. Suva
    • , Aviv Regev
    • , Charles D. Stiles
    • , Mark W. Kieran
    • , Liliana Goumnerova
    • , Keith L. Ligon
    • , Alex K. Shalek
    • , Pratiti Bandopadhayay
    •  & Rameen Beroukhim
  • Article
    | Open Access

    Gene activation requires an increase of successful initiation events. Here, by employing a genome-wide kinetic analysis of transcription, the authors showed that gene activation generally requires a decrease in RNA Polymerase II (Pol II) promoter-proximal pausing while transcription of enhancer elements is not limited by Pol II pausing.

    • Saskia Gressel
    • , Björn Schwalb
    •  & Patrick Cramer
  • Article
    | Open Access

    Interpreting genetic variation in the noncoding genome remains challenging, with functional effects difficult to predict. Here, the authors perform saturation mutagenesis combined with massively parallel reporter assays for 20 disease-associated regulatory elements, quantifying the effects of over 30,000 variants.

    • Martin Kircher
    • , Chenling Xiong
    • , Beth Martin
    • , Max Schubach
    • , Fumitaka Inoue
    • , Robert J. A. Bell
    • , Joseph F. Costello
    • , Jay Shendure
    •  & Nadav Ahituv
  • Article
    | Open Access

    The Oxford Nanopore system is capable of direct RNA sequencing but complex transcriptome analysis still remains to be thoroughly investigated. Here the authors perform sequencing of native RNA as well as cDNA to characterise the strengths and weaknesses of the system.

    • Charlotte Soneson
    • , Yao Yao
    • , Anna Bratus-Neuenschwander
    • , Andrea Patrignani
    • , Mark D. Robinson
    •  & Shobbir Hussain
  • Article
    | Open Access

    PIWI-interacting RNAs (piRNAs) are ~25–33 nt small RNAs expressed in animal germ cells. Here, the authors develop a single-cell small RNA sequencing method and report that a class of ~20-nt piRNAs lacking 3′ end 2′-O-methylation are associated with PIWIL3 protein and predominantly expressed in human and monkey oocytes.

    • Qiyuan Yang
    • , Ronghong Li
    • , Qifeng Lyu
    • , Li Hou
    • , Zhen Liu
    • , Qiang Sun
    • , Miao Liu
    • , Huijuan Shi
    • , Beiying Xu
    • , Mingru Yin
    • , Zhiguang Yan
    • , Ying Huang
    • , Mofang Liu
    • , Yiping Li
    •  & Ligang Wu
  • Article
    | Open Access

    The liver parenchyma consists of several cell types, but the origin of this tissue in humans is unclear. Here, the authors perform single cell RNA sequencing of human fetal and adult liver to identify a hepatobiliary hybrid progenitor population of cells, which have a similar gene signature to mouse oval cells.

    • Joe M. Segal
    • , Deniz Kent
    • , Daniel J. Wesche
    • , Soon Seng Ng
    • , Maria Serra
    • , Bénédicte Oulès
    • , Gozde Kar
    • , Guy Emerton
    • , Samuel J. I. Blackford
    • , Spyros Darmanis
    • , Rosa Miquel
    • , Tu Vinh Luong
    • , Ryo Yamamoto
    • , Andrew Bonham
    • , Wayel Jassem
    • , Nigel Heaton
    • , Alessandra Vigilante
    • , Aileen King
    • , Rocio Sancho
    • , Sarah Teichmann
    • , Stephen R. Quake
    • , Hiromitsu Nakauchi
    •  & S. Tamir Rashid
  • Article
    | Open Access

    To be able to use infectious disease next generation sequencing as a diagnostic tool, appropriate reference datasets are required. Here, Sichtig et al. describe FDA-ARGOS, a reference database for high-quality microbial reference genomes, and demonstrate its utility on the example of two use cases.

    • Heike Sichtig
    • , Timothy Minogue
    • , Yi Yan
    • , Christopher Stefan
    • , Adrienne Hall
    • , Luke Tallon
    • , Lisa Sadzewicz
    • , Suvarna Nadendla
    • , William Klimke
    • , Eneida Hatcher
    • , Martin Shumway
    • , Dayanara Lebron Aldea
    • , Jonathan Allen
    • , Jeffrey Koehler
    • , Tom Slezak
    • , Stephen Lovell
    • , Randal Schoepp
    •  & Uwe Scherf
  • Article
    | Open Access

    Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Here, Avraham and colleagues present a deconvolution algorithm that uses single-cell RNA and bulk RNA sequencing measurements of pathogen-infected cells to predict disease risk outcomes.

    • Noa Bossel Ben-Moshe
    • , Shelly Hen-Avivi
    • , Natalia Levitin
    • , Dror Yehezkel
    • , Marije Oosting
    • , Leo A. B. Joosten
    • , Mihai G. Netea
    •  & Roi Avraham
  • 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
    • , Anton J. M. Larsson
    • , Michael Lidschreiber
    • , Oscar Andersson Forsman
    • , Katja Lidschreiber
    • , Patrick Cramer
    •  & Rickard Sandberg
  • Article
    | Open Access

    Single cell RNA sequencing generates short reads from one end of a template, providing incomplete transcript coverage and limiting identification of diverse sequences such as antigen receptors. Here the authors combine long read nanopore sequencing with short read profiling of barcoded libraries to generate full-length antigen receptor sequences.

    • Mandeep Singh
    • , Ghamdan Al-Eryani
    • , Shaun Carswell
    • , James M. Ferguson
    • , James Blackburn
    • , Kirston Barton
    • , Daniel Roden
    • , Fabio Luciani
    • , Tri Giang Phan
    • , Simon Junankar
    • , Katherine Jackson
    • , Christopher C. Goodnow
    • , Martin A. Smith
    •  & Alexander Swarbrick
  • Article
    | Open Access

    Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”

    • Vincenzo Salpietro
    • , Christine L. Dixon
    • , Hui Guo
    • , Oscar D. Bello
    • , Jana Vandrovcova
    • , Stephanie Efthymiou
    • , Reza Maroofian
    • , Gali Heimer
    • , Lydie Burglen
    • , Stephanie Valence
    • , Erin Torti
    • , Moritz Hacke
    • , Julia Rankin
    • , Huma Tariq
    • , Estelle Colin
    • , Vincent Procaccio
    • , Pasquale Striano
    • , Kshitij Mankad
    • , Andreas Lieb
    • , Sharon Chen
    • , Laura Pisani
    • , Conceicao Bettencourt
    • , Roope Männikkö
    • , Andreea Manole
    • , Alfredo Brusco
    • , Enrico Grosso
    • , Giovanni Battista Ferrero
    • , Judith Armstrong-Moron
    • , Sophie Gueden
    • , Omer Bar-Yosef
    • , Michal Tzadok
    • , Kristin G. Monaghan
    • , Teresa Santiago-Sim
    • , Richard E. Person
    • , Megan T. Cho
    • , Rebecca Willaert
    • , Yongjin Yoo
    • , Jong-Hee Chae
    • , Yingting Quan
    • , Huidan Wu
    • , Tianyun Wang
    • , Raphael A. Bernier
    • , Kun Xia
    • , Alyssa Blesson
    • , Mahim Jain
    • , Mohammad M. Motazacker
    • , Bregje Jaeger
    • , Amy L. Schneider
    • , Katja Boysen
    • , Alison M. Muir
    • , Candace T. Myers
    • , Ralitza H. Gavrilova
    • , Lauren Gunderson
    • , Laura Schultz-Rogers
    • , Eric W. Klee
    • , David Dyment
    • , Matthew Osmond
    • , Mara Parellada
    • , Cloe Llorente
    • , Javier Gonzalez-Peñas
    • , Angel Carracedo
    • , Arie Van Haeringen
    • , Claudia Ruivenkamp
    • , Caroline Nava
    • , Delphine Heron
    • , Rosaria Nardello
    • , Michele Iacomino
    • , Carlo Minetti
    • , Aldo Skabar
    • , Antonella Fabretto
    • , Michael G. Hanna
    • , Enrico Bugiardini
    • , Isabel Hostettler
    • , Benjamin O’Callaghan
    • , Alaa Khan
    • , Andrea Cortese
    • , Emer O’Connor
    • , Wai Y. Yau
    • , Thomas Bourinaris
    • , Rauan Kaiyrzhanov
    • , Viorica Chelban
    • , Monika Madej
    • , Maria C. Diana
    • , Maria S. Vari
    • , Marina Pedemonte
    • , Claudio Bruno
    • , Ganna Balagura
    • , Marcello Scala
    • , Chiara Fiorillo
    • , Lino Nobili
    • , Nancy T. Malintan
    • , Maria N. Zanetti
    • , Shyam S. Krishnakumar
    • , Gabriele Lignani
    • , James E. C. Jepson
    • , Paolo Broda
    • , Simona Baldassari
    • , Pia Rossi
    • , Floriana Fruscione
    • , Francesca Madia
    • , Monica Traverso
    • , Patrizia De-Marco
    • , Belen Pérez-Dueñas
    • , Francina Munell
    • , Yamna Kriouile
    • , Mohamed El-Khorassani
    • , Blagovesta Karashova
    • , Daniela Avdjieva
    • , Hadil Kathom
    • , Radka Tincheva
    • , Lionel Van-Maldergem
    • , Wolfgang Nachbauer
    • , Sylvia Boesch
    • , Antonella Gagliano
    • , Elisabetta Amadori
    • , Jatinder S. Goraya
    • , Tipu Sultan
    • , Salman Kirmani
    • , Shahnaz Ibrahim
    • , Farida Jan
    • , Jun Mine
    • , Selina Banu
    • , Pierangelo Veggiotti
    • , Gian V. Zuccotti
    • , Michel D. Ferrari
    • , Arn M. J. Van Den Maagdenberg
    • , Alberto Verrotti
    • , Gian L. Marseglia
    • , Salvatore Savasta
    • , Miguel A. Soler
    • , Carmela Scuderi
    • , Eugenia Borgione
    • , Roberto Chimenz
    • , Eloisa Gitto
    • , Valeria Dipasquale
    • , Alessia Sallemi
    • , Monica Fusco
    • , Caterina Cuppari
    • , Maria C. Cutrupi
    • , Martino Ruggieri
    • , Armando Cama
    • , Valeria Capra
    • , Niccolò E. Mencacci
    • , Richard Boles
    • , Neerja Gupta
    • , Madhulika Kabra
    • , Savvas Papacostas
    • , Eleni Zamba-Papanicolaou
    • , Efthymios Dardiotis
    • , Shazia Maqbool
    • , Nuzhat Rana
    • , Osama Atawneh
    • , Shen Y. Lim
    • , Farooq Shaikh
    • , George Koutsis
    • , Marianthi Breza
    • , Domenico A. Coviello
    • , Yves A. Dauvilliers
    • , Issam AlKhawaja
    • , Mariam AlKhawaja
    • , Fuad Al-Mutairi
    • , Tanya Stojkovic
    • , Veronica Ferrucci
    • , Massimo Zollo
    • , Fowzan S. Alkuraya
    • , Maria Kinali
    • , Hamed Sherifa
    • , Hanene Benrhouma
    • , Ilhem B. Y. Turki
    • , Meriem Tazir
    • , Makram Obeid
    • , Sophia Bakhtadze
    • , Nebal W. Saadi
    • , Maha S. Zaki
    • , Chahnez C. Triki
    • , Fabio Benfenati
    • , Stefano Gustincich
    • , Majdi Kara
    • , Vincenzo Belcastro
    • , Nicola Specchio
    • , Giuseppe Capovilla
    • , Ehsan G. Karimiani
    • , Ahmed M. Salih
    • , Njideka U. Okubadejo
    • , Oluwadamilola O. Ojo
    • , Olajumoke O. Oshinaike
    • , Olapeju Oguntunde
    • , Kolawole Wahab
    • , Abiodun H. Bello
    • , Sanni Abubakar
    • , Yahaya Obiabo
    • , Ernest Nwazor
    • , Oluchi Ekenze
    • , Uduak Williams
    • , Alagoma Iyagba
    • , Lolade Taiwo
    • , Morenikeji Komolafe
    • , Konstantin Senkevich
    • , Chingiz Shashkin
    • , Nazira Zharkynbekova
    • , Kairgali Koneyev
    • , Ganieva Manizha
    • , Maksud Isrofilov
    • , Ulviyya Guliyeva
    • , Kamran Salayev
    • , Samson Khachatryan
    • , Salvatore Rossi
    • , Gabriella Silvestri
    • , Nourelhoda Haridy
    • , Luca A. Ramenghi
    • , Georgia Xiromerisiou
    • , Emanuele David
    • , Mhammed Aguennouz
    • , Liana Fidani
    • , Cleanthe Spanaki
    • , Arianna Tucci
    • , Miquel Raspall-Chaure
    • , Michael Chez
    • , Anne Tsai
    • , Emily Fassi
    • , Marwan Shinawi
    • , John N. Constantino
    • , Rita De Zorzi
    • , Sara Fortuna
    • , Fernando Kok
    • , Boris Keren
    • , Dominique Bonneau
    • , Murim Choi
    • , Bruria Benzeev
    • , Federico Zara
    • , Heather C. Mefford
    • , Ingrid E. Scheffer
    • , Jill Clayton-Smith
    • , Alfons Macaya
    • , James E. Rothman
    • , Evan E. Eichler
    • , Dimitri M. Kullmann
    •  & Henry Houlden
  • Article
    | Open Access

    Whole-genome sequencing data reveals a large number of variants for testing their associations with phenotypic traits and diseases. Here, the authors develop WGScan, a statistical method for detecting the existence and estimating the locations of the association signal at genome-wide scale.

    • Zihuai He
    • , Bin Xu
    • , Joseph Buxbaum
    •  & Iuliana Ionita-Laza
  • Article
    | Open Access

    A major bottleneck in using DNA as a data storage medium is the slowness of sequencing. Here the authors decode 1.67 megabytes of information using a portable nanopore platform with an assembly strategy for increased throughput.

    • Randolph Lopez
    • , Yuan-Jyue Chen
    • , Siena Dumas Ang
    • , Sergey Yekhanin
    • , Konstantin Makarychev
    • , Miklos Z Racz
    • , Georg Seelig
    • , Karin Strauss
    •  & Luis Ceze
  • Article
    | Open Access

    The sinus node generates rhythmic heartbeat but the molecular basis of pacemaking is still under debate. Here, the authors combine quantitative proteomics and single-nucleus transcriptomics to characterize the molecular composition of the sinus node and provide insights into the underpinnings of pacemaking.

    • Nora Linscheid
    • , Sunil Jit R. J. Logantha
    • , Pi Camilla Poulsen
    • , Shanzhuo Zhang
    • , Maren Schrölkamp
    • , Kristoffer Lihme Egerod
    • , Jonatan James Thompson
    • , Ashraf Kitmitto
    • , Gina Galli
    • , Martin J. Humphries
    • , Henggui Zhang
    • , Tune H. Pers
    • , Jesper Velgaard Olsen
    • , Mark Boyett
    •  & Alicia Lundby
  • Article
    | Open Access

    Single-cell studies in solid tissues remain challenging and have benefited from the development of single-nuclei RNA sequencing strategies. Here Lake et al. apply single-nucleus RNA sequencing to human kidney tissues to provide a comprehensive molecular and cellular atlas of the human kidney, with potential implications for the understanding of kidney physiology and disease.

    • Blue B. Lake
    • , Song Chen
    • , Masato Hoshi
    • , Nongluk Plongthongkum
    • , Diane Salamon
    • , Amanda Knoten
    • , Anitha Vijayan
    • , Ramakrishna Venkatesh
    • , Eric H. Kim
    • , Derek Gao
    • , Joseph Gaut
    • , Kun Zhang
    •  & Sanjay Jain
  • Article
    | Open Access

    The transcriptional signature of embryonic lethality has not been defined. Here, the authors, as part of the Deciphering the Mechanisms of Developmental Disorders programme, define genes causing murine embryonic lethality around E9.5 and identify developmental delay transcriptional signatures.

    • John E. Collins
    • , Richard J. White
    • , Nicole Staudt
    • , Ian M. Sealy
    • , Ian Packham
    • , Neha Wali
    • , Catherine Tudor
    • , Cecilia Mazzeo
    • , Angela Green
    • , Emma Siragher
    • , Edward Ryder
    • , Jacqueline K. White
    • , Irene Papatheodoru
    • , Amy Tang
    • , Anja Füllgrabe
    • , Konstantinos Billis
    • , Stefan H. Geyer
    • , Wolfgang J. Weninger
    • , Antonella Galli
    • , Myriam Hemberger
    • , Derek L. Stemple
    • , Elizabeth Robertson
    • , James C. Smith
    • , Timothy Mohun
    • , David J. Adams
    •  & Elisabeth M. Busch-Nentwich
  • Article
    | Open Access

    The dynamics of HIV-1 DNA sequences early after HIV-1 transmission remains poorly characterized. Here, the authors perform a longitudinal evaluation of HIV-1 DNA sequences in subtype C-infected individuals during acute infection, providing a landscape of the nature and evolution of the very early viral genome.

    • Guinevere Q. Lee
    • , Kavidha Reddy
    • , Kevin B. Einkauf
    • , Kamini Gounder
    • , Joshua M. Chevalier
    • , Krista L. Dong
    • , Bruce D. Walker
    • , Xu G. Yu
    • , Thumbi Ndung’u
    •  & Mathias Lichterfeld
  • Article
    | Open Access

    Simulated single cell RNA sequencing data is useful for method development and comparison. Here, the authors developed SymSim, a simulator that explicitly models the main factors of variation in single cell data.

    • Xiuwei Zhang
    • , Chenling Xu
    •  & Nir Yosef
  • Article
    | Open Access

    Many causative genes are known for epileptic or developmental and epileptic encephalopathies (EE/DEE) yet a genetic diagnosis cannot be made for many patients. Here, the authors analyse whole exome sequencing data from a Japanese case−control cohort to identify common, rare and ultra-rare coding variants associated with EE/DEE.

    • Atsushi Takata
    • , Mitsuko Nakashima
    • , Hirotomo Saitsu
    • , Takeshi Mizuguchi
    • , Satomi Mitsuhashi
    • , Yukitoshi Takahashi
    • , Nobuhiko Okamoto
    • , Hitoshi Osaka
    • , Kazuyuki Nakamura
    • , Jun Tohyama
    • , Kazuhiro Haginoya
    • , Saoko Takeshita
    • , Ichiro Kuki
    • , Tohru Okanishi
    • , Tomohide Goto
    • , Masayuki Sasaki
    • , Yasunari Sakai
    • , Noriko Miyake
    • , Satoko Miyatake
    • , Naomi Tsuchida
    • , Kazuhiro Iwama
    • , Gaku Minase
    • , Futoshi Sekiguchi
    • , Atsushi Fujita
    • , Eri Imagawa
    • , Eriko Koshimizu
    • , Yuri Uchiyama
    • , Kohei Hamanaka
    • , Chihiro Ohba
    • , Toshiyuki Itai
    • , Hiromi Aoi
    • , Ken Saida
    • , Tomohiro Sakaguchi
    • , Kouhei Den
    • , Rina Takahashi
    • , Hiroko Ikeda
    • , Tokito Yamaguchi
    • , Kazuki Tsukamoto
    • , Shinsaku Yoshitomi
    • , Taikan Oboshi
    • , Katsumi Imai
    • , Tomokazu Kimizu
    • , Yu Kobayashi
    • , Masaya Kubota
    • , Hirofumi Kashii
    • , Shimpei Baba
    • , Mizue Iai
    • , Ryutaro Kira
    • , Munetsugu Hara
    • , Masayasu Ohta
    • , Yohane Miyata
    • , Rie Miyata
    • , Jun-ichi Takanashi
    • , Jun Matsui
    • , Kenji Yokochi
    • , Masayuki Shimono
    • , Masano Amamoto
    • , Rumiko Takayama
    • , Shinichi Hirabayashi
    • , Kaori Aiba
    • , Hiroshi Matsumoto
    • , Shin Nabatame
    • , Takashi Shiihara
    • , Mitsuhiro Kato
    •  & Naomichi Matsumoto
  • Article
    | Open Access

    Measuring relative frequencies of DNA double-strand breaks between loci does not provide the full physiological relevance of those breaks. Here Rowicka and colleagues present qDSB-Seq method which uses spike-in double-strand breaks induced by a restriction enzyme to accurately quantify DNA damage.

    • Yingjie Zhu
    • , Anna Biernacka
    • , Benjamin Pardo
    • , Norbert Dojer
    • , Romain Forey
    • , Magdalena Skrzypczak
    • , Bernard Fongang
    • , Jules Nde
    • , Razie Yousefi
    • , Philippe Pasero
    • , Krzysztof Ginalski
    •  & Maga Rowicka
  • Article
    | Open Access

    Complete gene expression deconvolution remains a challenging problem. Here, the authors provide a solution based on the recognition that expression levels of cell type specific genes are mutually linear across mixtures and mutually linear gene clusters correspond to cell type-specific signatures.

    • Konstantin Zaitsev
    • , Monika Bambouskova
    • , Amanda Swain
    •  & Maxim N. Artyomov
  • Article
    | Open Access

    Transcriptome analysis of circulating tumor cells (CTCs) provides insights into monitoring target therapeutics and underlying tumor metastasis. Here the authors present Hydro-Seq, a contamination-free high-throughput hydrodynamic scRNA-seq barcoding technique for rare CTCs.

    • Yu-Heng Cheng
    • , Yu-Chih Chen
    • , Eric Lin
    • , Riley Brien
    • , Seungwon Jung
    • , Yu-Ting Chen
    • , Woncheol Lee
    • , Zhijian Hao
    • , Saswat Sahoo
    • , Hyun Min Kang
    • , Jason Cong
    • , Monika Burness
    • , Sunitha Nagrath
    • , Max S. Wicha
    •  & Euisik Yoon
  • Article
    | Open Access

    Alignment is an important stage in the analysis of sequencing data. Here, the authors present a fast and accurate alignment approach suitable for long and short reads, and introduce two line sweep-based techniques which can replace the often-used chaining approach.

    • Markus Schmidt
    • , Klaus Heese
    •  & Arne Kutzner
  • Article
    | Open Access

    The development of site-specific recombinases as genome editing tools is limited by the difficulty of altering their DNA sequence specificity. Here the authors present Rec-seq, a method for identifying specificity determinants and off-target substrates of recombinases in an unbiased manner.

    • Jeffrey L. Bessen
    • , Lena K. Afeyan
    • , Vlado Dančík
    • , Luke W. Koblan
    • , David B. Thompson
    • , Chas Leichner
    • , Paul A. Clemons
    •  & David R. Liu
  • Article
    | Open Access

    The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.

    • Huidong Chen
    • , Luca Albergante
    • , Jonathan Y. Hsu
    • , Caleb A. Lareau
    • , Giosuè Lo Bosco
    • , Jihong Guan
    • , Shuigeng Zhou
    • , Alexander N. Gorban
    • , Daniel E. Bauer
    • , Martin J. Aryee
    • , David M. Langenau
    • , Andrei Zinovyev
    • , Jason D. Buenrostro
    • , Guo-Cheng Yuan
    •  & Luca Pinello
  • Article
    | Open Access

    Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

    • Mark J. P. Chaisson
    • , Ashley D. Sanders
    • , Xuefang Zhao
    • , Ankit Malhotra
    • , David Porubsky
    • , Tobias Rausch
    • , Eugene J. Gardner
    • , Oscar L. Rodriguez
    • , Li Guo
    • , Ryan L. Collins
    • , Xian Fan
    • , Jia Wen
    • , Robert E. Handsaker
    • , Susan Fairley
    • , Zev N. Kronenberg
    • , Xiangmeng Kong
    • , Fereydoun Hormozdiari
    • , Dillon Lee
    • , Aaron M. Wenger
    • , Alex R. Hastie
    • , Danny Antaki
    • , Thomas Anantharaman
    • , Peter A. Audano
    • , Harrison Brand
    • , Stuart Cantsilieris
    • , Han Cao
    • , Eliza Cerveira
    • , Chong Chen
    • , Xintong Chen
    • , Chen-Shan Chin
    • , Zechen Chong
    • , Nelson T. Chuang
    • , Christine C. Lambert
    • , Deanna M. Church
    • , Laura Clarke
    • , Andrew Farrell
    • , Joey Flores
    • , Timur Galeev
    • , David U. Gorkin
    • , Madhusudan Gujral
    • , Victor Guryev
    • , William Haynes Heaton
    • , Jonas Korlach
    • , Sushant Kumar
    • , Jee Young Kwon
    • , Ernest T. Lam
    • , Jong Eun Lee
    • , Joyce Lee
    • , Wan-Ping Lee
    • , Sau Peng Lee
    • , Shantao Li
    • , Patrick Marks
    • , Karine Viaud-Martinez
    • , Sascha Meiers
    • , Katherine M. Munson
    • , Fabio C. P. Navarro
    • , Bradley J. Nelson
    • , Conor Nodzak
    • , Amina Noor
    • , Sofia Kyriazopoulou-Panagiotopoulou
    • , Andy W. C. Pang
    • , Yunjiang Qiu
    • , Gabriel Rosanio
    • , Mallory Ryan
    • , Adrian Stütz
    • , Diana C. J. Spierings
    • , Alistair Ward
    • , AnneMarie E. Welch
    • , Ming Xiao
    • , Wei Xu
    • , Chengsheng Zhang
    • , Qihui Zhu
    • , Xiangqun Zheng-Bradley
    • , Ernesto Lowy
    • , Sergei Yakneen
    • , Steven McCarroll
    • , Goo Jun
    • , Li Ding
    • , Chong Lek Koh
    • , Bing Ren
    • , Paul Flicek
    • , Ken Chen
    • , Mark B. Gerstein
    • , Pui-Yan Kwok
    • , Peter M. Lansdorp
    • , Gabor T. Marth
    • , Jonathan Sebat
    • , Xinghua Shi
    • , Ali Bashir
    • , Kai Ye
    • , Scott E. Devine
    • , Michael E. Talkowski
    • , Ryan E. Mills
    • , Tobias Marschall
    • , Jan O. Korbel
    • , Evan E. Eichler
    •  & Charles Lee