Genetics

  • Article
    | Open Access

    The BEN-solo proteins—including Insensitive (Insv), Elba1 and Elba2—function in both transcriptional repression and chromatin insulation. Here, the authors investigate the role of these proteins in Drosophila embryos, finding that ELBA and Insv function as general insulators and partition active chromatin to ensure proper gene activation in Drosophila.

    • Malin Ueberschär
    • , Huazhen Wang
    • , Chun Zhang
    • , Shu Kondo
    • , Tsutomu Aoki
    • , Paul Schedl
    • , Eric C. Lai
    • , Jiayu Wen
    •  & Qi Dai
  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

    • Mohammad S. Esfahani
    • , Luke J. Lee
    • , Young-Jun Jeon
    • , Ryan A. Flynn
    • , Henning Stehr
    • , Angela B. Hui
    • , Noriko Ishisoko
    • , Eric Kildebeck
    • , Aaron M. Newman
    • , Scott V. Bratman
    • , Matthew H. Porteus
    • , Howard Y. Chang
    • , Ash A. Alizadeh
    •  & Maximilian Diehn
  • Article
    | Open Access

    Although many species-specific imprinted genes have been identified, how the evolutionary switch from biallelic to imprinted expression occurs is still unknown. Here authors find that lineage-specific ERVs active as oocyte promoters can induce de novo DNA methylation at gDMRs and imprinting.

    • Aaron B. Bogutz
    • , Julie Brind’Amour
    • , Hisato Kobayashi
    • , Kristoffer N. Jensen
    • , Kazuhiko Nakabayashi
    • , Hiroo Imai
    • , Matthew C. Lorincz
    •  & Louis Lefebvre
  • Article
    | Open Access

    Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

    • Makoto Hirata
    • , Naofumi Asano
    • , Kotoe Katayama
    • , Akihiko Yoshida
    • , Yusuke Tsuda
    • , Masaya Sekimizu
    • , Sachiyo Mitani
    • , Eisuke Kobayashi
    • , Motokiyo Komiyama
    • , Hiroyuki Fujimoto
    • , Takahiro Goto
    • , Yukihide Iwamoto
    • , Norifumi Naka
    • , Shintaro Iwata
    • , Yoshihiro Nishida
    • , Toru Hiruma
    • , Hiroaki Hiraga
    • , Hirotaka Kawano
    • , Toru Motoi
    • , Yoshinao Oda
    • , Daisuke Matsubara
    • , Masashi Fujita
    • , Tatsuhiro Shibata
    • , Hidewaki Nakagawa
    • , Robert Nakayama
    • , Tadashi Kondo
    • , Seiya Imoto
    • , Satoru Miyano
    • , Akira Kawai
    • , Rui Yamaguchi
    • , Hitoshi Ichikawa
    •  & Koichi Matsuda
  • Article
    | Open Access

    Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.

    • Osamu Iwasaki
    • , Hideki Tanizawa
    • , Kyoung-Dong Kim
    • , Andrew Kossenkov
    • , Timothy Nacarelli
    • , Sanki Tashiro
    • , Sonali Majumdar
    • , Louise C. Showe
    • , Rugang Zhang
    •  & Ken-ichi Noma
  • Article
    | Open Access

    XACT is a primate-specific TE-derived lncRNA that coats active X chromosomes in pluripotent cells and may contribute to species-specific regulation of X chromosome inactivation. Here, the authors investigate TEs associated with the XACT locus and identify a critical enhancer for its regulation, which evolved from an ancestral group of mammalian endogenous retroviruses, prior to the emergence of XACT.

    • Miguel Casanova
    • , Madeleine Moscatelli
    • , Louis Édouard Chauvière
    • , Christophe Huret
    • , Julia Samson
    • , Tharvesh Moideen Liyakat Ali
    • , Olga Rosspopoff
    •  & Claire Rougeulle
  • Article
    | Open Access

    Effective precision medicine strategies rely on the ability to predict tumour behaviour based on molecular characteristics. Here, the authors build models to predict multiple distinct gene expression patterns using DNA copy number alterations

    • Youli Xia
    • , Cheng Fan
    • , Katherine A. Hoadley
    • , Joel S. Parker
    •  & Charles M. Perou
  • Article
    | Open Access

    Long primary transcripts of microRNAs are co-transcriptionally cleaved by the enzyme Drosha. Here the authors suggest that DNA methylation in miRNA loci in mammalian cells increases Drosha binding, slowing RNA polymerase II elongation to enhance miRNA biogenesis.

    • Ohad Glaich
    • , Shivang Parikh
    • , Rachel E. Bell
    • , Keren Mekahel
    • , Maya Donyo
    • , Yodfat Leader
    • , Ronna Shayevitch
    • , Danna Sheinboim
    • , Sivan Yannai
    • , Dror Hollander
    • , Ze’ev Melamed
    • , Galit Lev-Maor
    • , Gil Ast
    •  & Carmit Levy
  • Article
    | Open Access

    N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are eukaryotic mRNA modifications. Here the authors develop m6A-Crosslinking-Exonuclease-sequencing to map quantitative methylome changes at single-base-resolution after individually knocking out each known methyltransferase or demethylase.

    • Casslynn W. Q. Koh
    • , Yeek Teck Goh
    •  & W. S. Sho Goh
  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    • , Vasavi Sundaram
    •  & Ting Wang
  • Article
    | Open Access

    The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

    • Ian Casci
    • , Karthik Krishnamurthy
    • , Sukhleen Kour
    • , Vadreenath Tripathy
    • , Nandini Ramesh
    • , Eric N. Anderson
    • , Lara Marrone
    • , Rogan A. Grant
    • , Stacie Oliver
    • , Lauren Gochenaur
    • , Krishani Patel
    • , Jared Sterneckert
    • , Amanda M. Gleixner
    • , Christopher J. Donnelly
    • , Marc-David Ruepp
    • , Antonella M. Sini
    • , Emanuela Zuccaro
    • , Maria Pennuto
    • , Piera Pasinelli
    •  & Udai Bhan Pandey
  • Article
    | Open Access

    Class 1 CRISPR systems are not as developed for genome editing as Class 2 systems are. Here the authors show that Cas3 can be used to generate functional knockouts and knock-ins, as well as Cas3-mediated exon-skipping in DMD cells.

    • Hiroyuki Morisaka
    • , Kazuto Yoshimi
    • , Yuya Okuzaki
    • , Peter Gee
    • , Yayoi Kunihiro
    • , Ekasit Sonpho
    • , Huaigeng Xu
    • , Noriko Sasakawa
    • , Yuki Naito
    • , Shinichiro Nakada
    • , Takashi Yamamoto
    • , Shigetoshi Sano
    • , Akitsu Hotta
    • , Junji Takeda
    •  & Tomoji Mashimo
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    • , Cindy S. Chu
    • , Kanokpich Puaprasert
    • , Jureeporn Duanguppama
    • , Nicholas P. J. Day
    • , Francois Nosten
    • , Daniel E. Neafsey
    • , Caroline O. Buckee
    • , Mallika Imwong
    •  & Nicholas J. White
  • Article
    | Open Access

    Senescence of metabolically active cells is a process linked to ageing. Here the authors reveal that CSB is required to block replicative senescence, and epigenetic control of CSB downregulation triggers proliferative arrest in a p21-dependent manner.

    • Clément Crochemore
    • , Cristina Fernández-Molina
    • , Benjamin Montagne
    • , Audrey Salles
    •  & Miria Ricchetti
  • Article
    | Open Access

    Unlike the other domesticated maize, sweet maize and popcorn retain tillering growth habit, but the underlying mechanism is unknown. Here, the authors identify a transcription factor tin1 that maintains outgrowth of tiller independent of tb1 and show its conservation in foxtail millet and rice.

    • Xuan Zhang
    • , Zhelong Lin
    • , Jian Wang
    • , Hangqin Liu
    • , Leina Zhou
    • , Shuyang Zhong
    • , Yan Li
    • , Can Zhu
    • , Jiacheng Liu
    •  & Zhongwei Lin
  • 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

    Siblings of those with autism spectrum disorder (ASD) have increased likelihood of ASD or related subclinical traits. Here, studying 253 ASD families, D’Abate et al. test the predictive value of genomic copy number variation involving ASD-associated loci, with confirmation in a second cohort.

    • L. D’Abate
    • , S. Walker
    • , R. K. C. Yuen
    • , K. Tammimies
    • , J. A. Buchanan
    • , R. W. Davies
    • , B. Thiruvahindrapuram
    • , J. Wei
    • , J. Brian
    • , S. E. Bryson
    • , K. Dobkins
    • , J. Howe
    • , R. Landa
    • , J. Leef
    • , D. Messinger
    • , S. Ozonoff
    • , I. M. Smith
    • , W. L. Stone
    • , Z. E. Warren
    • , G. Young
    • , L. Zwaigenbaum
    •  & S. W. Scherer
  • Article
    | Open Access

    The basis of sexual dimorphism in non-model species may be elusive, in part due to a lack of genomic and molecular resources. Here, Li et al. report a high-quality anuran genome and reveal candidate genes and pathways associated with shaping sexually dimorphic nuptial spines in a moustache toad.

    • Jun Li
    • , Haiyan Yu
    • , Wenxia Wang
    • , Chao Fu
    • , Wei Zhang
    • , Fengming Han
    •  & Hua Wu
  • Article
    | Open Access

    MLL family histone methyltransferases deposit histone H3 Lys4 mono-/di-/tri-methylation and regulate gene expression in mammals. Here the authors report the single-particle cryo-EM structure of the NCP-bound human MLL1 core complex, shedding light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

    • Sang Ho Park
    • , Alex Ayoub
    • , Young-Tae Lee
    • , Jing Xu
    • , Hanseong Kim
    • , Wei Zheng
    • , Biao Zhang
    • , Liang Sha
    • , Sojin An
    • , Yang Zhang
    • , Michael A. Cianfrocco
    • , Min Su
    • , Yali Dou
    •  & Uhn-Soo Cho
  • Article
    | Open Access

    RNA polymerase I (Pol I) catalyses the transcription of pre-ribosomal RNA and for transcription initiation Pol I assembles with core factor and Rrn3 on the rDNA core promoter. Here the authors provide insights into the molecular mechanism of promoter opening by Pol I by determining the cryo-EM structures of two closed, two intermediate and two open Pol I pre-initiation complexes.

    • Yashar Sadian
    • , Florence Baudin
    • , Lucas Tafur
    • , Brice Murciano
    • , Rene Wetzel
    • , Felix Weis
    •  & Christoph W. Müller
  • Article
    | Open Access

    The adult mammalian inner ear cells cannot regenerate nor proliferate. Here, the authors show that co-activation of Myc and NOTCH pathways can stimulate proliferation of inner ear sensory epithelial cells, which can be induced to become hair cell-like cells in vitro and in vivo.

    • Yilai Shu
    • , Wenyan Li
    • , Mingqian Huang
    • , Yi-Zhou Quan
    • , Deborah Scheffer
    • , Chunjie Tian
    • , Yong Tao
    • , Xuezhong Liu
    • , Konrad Hochedlinger
    • , Artur A. Indzhykulian
    • , Zhengmin Wang
    • , Huawei Li
    •  & Zheng-Yi Chen
  • Article
    | Open Access

    Bacteria use CRISPR-Cas systems to protect themselves against viral infections. Here, Watson et al. show that a type I CRISPR-Cas system can induce abortive viral infection, where infected cells do not survive but viral propagation is decreased, thus protecting the bacterial population.

    • Bridget N. J. Watson
    • , Reuben B. Vercoe
    • , George P. C. Salmond
    • , Edze R. Westra
    • , Raymond H. J Staals
    •  & Peter C. Fineran
  • Article
    | Open Access

    Avian influenza A virus (IAV) strains replicate poorly in mammalian hosts, but mechanisms underlying species restriction are incompletely understood. Here, Bogdanow et al. show that avian and mammalian adapted IAV strains have evolved different RNA structure features for regulation of M segment RNA splicing.

    • Boris Bogdanow
    • , Xi Wang
    • , Katrin Eichelbaum
    • , Anne Sadewasser
    • , Immanuel Husic
    • , Katharina Paki
    • , Matthias Budt
    • , Martha Hergeselle
    • , Barbara Vetter
    • , Jingyi Hou
    • , Wei Chen
    • , Lüder Wiebusch
    • , Irmtraud M. Meyer
    • , Thorsten Wolff
    •  & Matthias Selbach
  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    • , Catherine Gong
    • , Lisa Zhang
    • , Emmanuel Edusei
    • , Jennifer Huang
    • , Shady Albakry
    • , Michael J. Satlin
    • , Lars F. Westblade
    • , Carl Crawford
    • , Darshana M. Dadhania
    • , Michelle Lubetzky
    • , Ying Taur
    • , Eric Littman
    • , Lilan Ling
    • , Philip Burnham
    • , Iwijn De Vlaminck
    • , Eric Pamer
    • , Manikkam Suthanthiran
    •  & John Richard Lee
  • 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

    CRISPR-Cas systems have well characterized, modular structures. Here the authors use that architecture to design a Cas12a library of 560 synthetic chimeras, with altered PAM preferences and specificities.

    • R. M. Liu
    • , L. L. Liang
    • , E. Freed
    • , H. Chang
    • , E. Oh
    • , Z. Y. Liu
    • , A. Garst
    • , C. A. Eckert
    •  & R. T. Gill
  • Article
    | Open Access

    Sequencing cancer genomes reveals low frequency novel somatic variants without known function. Here, the authors leverage statistical methodology from the fields of computational linguistics and ecology to highlight the potentially important signals harboured by these novel variants that are often dismissed.

    • Saptarshi Chakraborty
    • , Arshi Arora
    • , Colin B. Begg
    •  & Ronglai Shen
  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    • , Joshua D. Ginzel
    • , Veronica Lubkov
    • , Wendy L. Roberts
    • , P. J. Nicholls
    • , Cheryl Bock
    • , Mei Lang Flowers
    • , Richard J. von Furstenberg
    • , Barry R. Stripp
    • , Pankaj Agarwal
    • , Alexander D. Borowsky
    • , Robert D. Cardiff
    • , Larry S. Barak
    • , Marc G. Caron
    • , H. Kim Lyerly
    •  & Joshua C. Snyder
  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    • , Yongge Zhao
    • , Mina O. Seedhom
    • , Christelle Harly
    • , Izumi Ohigashi
    • , Michael Kelly
    • , Yousuke Takahama
    • , Jonathan W. Yewdell
    • , Maggie Cam
    •  & Avinash Bhandoola
  • Article
    | Open Access

    Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.

    • Nhan Huynh
    • , Qiuxiang Ou
    • , Pendleton Cox
    • , Roland Lill
    •  & Kirst King-Jones
  • Article
    | Open Access

    Inducible genome editing systems often suffer from leakiness or reduced activity. Here the authors develop CRISPR-Switch, a Cre recombinase ON/OFF-controlled sgRNA cassette that allows consecutive editing of two loci.

    • Krzysztof Chylinski
    • , Maria Hubmann
    • , Ruth E. Hanna
    • , Connor Yanchus
    • , Georg Michlits
    • , Esther C. H. Uijttewaal
    • , John Doench
    • , Daniel Schramek
    •  & Ulrich Elling
  • Article
    | Open Access

    Songbirds have extensive germline–soma genome differences due to developmental elimination of a germline-specific chromosome (GRC). Here, the authors show that the GRC contains dozens of expressed developmental genes, some of which have been on the GRC since the ancestor of all songbirds.

    • Cormac M. Kinsella
    • , Francisco J. Ruiz-Ruano
    • , Anne-Marie Dion-Côté
    • , Alexander J. Charles
    • , Toni I. Gossmann
    • , Josefa Cabrero
    • , Dennis Kappei
    • , Nicola Hemmings
    • , Mirre J. P. Simons
    • , Juan Pedro M. Camacho
    • , Wolfgang Forstmeier
    •  & Alexander Suh
  • Article
    | Open Access

    The genomic and immune landscape of pre-invasive lung adenocarcinoma is poorly understood. Here, the authors perform exome and transcriptome sequencing on precursor legions and invasive lung adenocarcinomas, identifying recurrently mutated genes in pre/minimally invasive cases, and arm level alteration events linked to immune infiltration.

    • Haiquan Chen
    • , Jian Carrot-Zhang
    • , Yue Zhao
    • , Haichuan Hu
    • , Samuel S. Freeman
    • , Su Yu
    • , Gavin Ha
    • , Alison M. Taylor
    • , Ashton C. Berger
    • , Lindsay Westlake
    • , Yuanting Zheng
    • , Jiyang Zhang
    • , Aruna Ramachandran
    • , Qiang Zheng
    • , Yunjian Pan
    • , Difan Zheng
    • , Shanbo Zheng
    • , Chao Cheng
    • , Muyu Kuang
    • , Xiaoyan Zhou
    • , Yang Zhang
    • , Hang Li
    • , Ting Ye
    • , Yuan Ma
    • , Zhendong Gao
    • , Xiaoting Tao
    • , Han Han
    • , Jun Shang
    • , Ying Yu
    • , Ding Bao
    • , Yechao Huang
    • , Xiangnan Li
    • , Yawei Zhang
    • , Jiaqing Xiang
    • , Yihua Sun
    • , Yuan Li
    • , Andrew D. Cherniack
    • , Joshua D. Campbell
    • , Leming Shi
    •  & Matthew Meyerson
  • Article
    | Open Access

    Acute Myeloid Leukemia (AML) develops following multiple mutations of differing impact. Here, the authors show that activating mutations of CSF3R co-operate with loss-of-function mutations of CEBPA to promote AML development through an enhancer-dependent mechanism.

    • Theodore P. Braun
    • , Mariam Okhovat
    • , Cody Coblentz
    • , Sarah A. Carratt
    • , Amy Foley
    • , Zachary Schonrock
    • , Brittany M. Smith
    • , Kimberly Nevonen
    • , Brett Davis
    • , Brianna Garcia
    • , Dorian LaTocha
    • , Benjamin R. Weeder
    • , Michal R. Grzadkowski
    • , Joey C. Estabrook
    • , Hannah G. Manning
    • , Kevin Watanabe-Smith
    • , Sophia Jeng
    • , Jenny L. Smith
    • , Amanda R. Leonti
    • , Rhonda E. Ries
    • , Shannon McWeeney
    • , Cristina Di Genua
    • , Roy Drissen
    • , Claus Nerlov
    • , Soheil Meshinchi
    • , Lucia Carbone
    • , Brian J. Druker
    •  & Julia E. Maxson
  • 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

    Tissue context can dictate why a gene can have seemingly opposing functions in different settings. ELF3 is tumor suppressive in many cancers of epithelial origin but in lung cancer, the authors describe an oncogenic role in the adenocarcinoma histology of non-small cell lung cancer.

    • Katey S. S. Enfield
    • , Erin A. Marshall
    • , Christine Anderson
    • , Kevin W. Ng
    • , Sara Rahmati
    • , Zhaolin Xu
    • , Megan Fuller
    • , Katy Milne
    • , Daniel Lu
    • , Rocky Shi
    • , David A. Rowbotham
    • , Daiana D. Becker-Santos
    • , Fraser D. Johnson
    • , John C. English
    • , Calum E. MacAulay
    • , Stephen Lam
    • , William W. Lockwood
    • , Raj Chari
    • , Aly Karsan
    • , Igor Jurisica
    •  & Wan L. Lam
  • 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

    In pancreatic cancer the Kras and Trp53 transgene driven KPC mouse model is used to experimentally study disease processes. Here, the authors analyse tumour evolution within the KPC model, finding both linear and branched evolution and highlighting the utility of this model in mechanistic research of tumour evolution.

    • Noushin Niknafs
    • , Yi Zhong
    • , John Alec Moral
    • , Lance Zhang
    • , Melody Xiaoshan Shao
    • , April Lo
    • , Alvin Makohon-Moore
    • , Christine A. Iacobuzio-Donahue
    •  & Rachel Karchin
  • Article
    | Open Access

    The neural tissues of coleoids have a greater fraction of nonsynonymous sites than synonymous sites subject to high levels of A-to-I RNA editing, a pattern thought to indicate widespread adaptive editing. Here the authors propose and provide evidence for an alternative, nonadaptive explanation.

    • Daohan Jiang
    •  & Jianzhi Zhang
  • Article
    | Open Access

    Relatively little is known about the complexity of regulatory evolution accompanying polyploid crop domestication. Here, using reciprocal hybrids between wild and domesticated allotetraploid cotton lines, the authors catalog cis and trans regulatory variants and show their equivalent effects on cotton fiber domestication.

    • Ying Bao
    • , Guanjing Hu
    • , Corrinne E. Grover
    • , Justin Conover
    • , Daojun Yuan
    •  & Jonathan F. Wendel
  • 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

    Machine learning algorithms can be trained to estimate age from brain structural MRI. Here, the authors introduce a new deep-learning-based age prediction approach, and then carry out a GWAS of the difference between predicted and chronological age, revealing two associated variants.

    • B. A. Jonsson
    • , G. Bjornsdottir
    • , T. E. Thorgeirsson
    • , L. M. Ellingsen
    • , G. Bragi Walters
    • , D. F. Gudbjartsson
    • , H. Stefansson
    • , K. Stefansson
    •  & M. O. Ulfarsson
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Article
    | Open Access

    There is disproportionally high cancer prevalence in males. Here, the authors analyse the tumour suppressor p53 in sporadic cancers, highlighting a higher incidence of its mutation in males. Males are further disadvantaged by a failure to shield against the expression of damaged X-linked genes in p53-networks. These factors likely contribute to sex-disparity.

    • Sue Haupt
    • , Franco Caramia
    • , Alan Herschtal
    • , Thierry Soussi
    • , Guillermina Lozano
    • , Hu Chen
    • , Han Liang
    • , Terence P. Speed
    •  & Ygal Haupt
  • Article
    | Open Access

    A significant proportion of the molecular evolution of bacteria and archaea occurs through gene gain and loss. Here Iranzo et al. develop a mathematical model that explains observed differential patterns of sequence evolution vs. gene content evolution as a consequence of homologous recombination.

    • Jaime Iranzo
    • , Yuri I. Wolf
    • , Eugene V. Koonin
    •  & Itamar Sela
  • Article
    | Open Access

    Stepwise acquisition of mutations gives rise to myelodysplastic syndrome (MDS) in older adults. Here, the authors infer the clonal hierarchy of 1809 MDS patients, revealing insights into the evolution of dominant/secondary mutations and how these impact clinical phenotypes like leukemic progression and therapy response.

    • Yasunobu Nagata
    • , Hideki Makishima
    • , Cassandra M. Kerr
    • , Bartlomiej P. Przychodzen
    • , Mai Aly
    • , Abhinav Goyal
    • , Hassan Awada
    • , Mohammad Fahad Asad
    • , Teodora Kuzmanovic
    • , Hiromichi Suzuki
    • , Tetsuichi Yoshizato
    • , Kenichi Yoshida
    • , Kenichi Chiba
    • , Hiroko Tanaka
    • , Yuichi Shiraishi
    • , Satoru Miyano
    • , Sudipto Mukherjee
    • , Thomas LaFramboise
    • , Aziz Nazha
    • , Mikkael A. Sekeres
    • , Tomas Radivoyevitch
    • , Torsten Haferlach
    • , Seishi Ogawa
    •  & Jaroslaw P. Maciejewski
  • Article
    | Open Access

    Several functions have been proposed for m6A in RNA metabolism, yet little is known regarding the specific functions of individual m6A readers. Here, the authors observe that the m6A reader YTHDC2 — which contains an RNA helicase domain — acts on the coding region to promotes mRNA translation by resolving secondary structures.

    • Yuanhui Mao
    • , Leiming Dong
    • , Xiao-Min Liu
    • , Jiayin Guo
    • , Honghui Ma
    • , Bin Shen
    •  & Shu-Bing Qian
  • Article
    | Open Access

    In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

    • Koustav Pal
    • , Mattia Forcato
    • , Daniel Jost
    • , Thomas Sexton
    • , Cédric Vaillant
    • , Elisa Salviato
    • , Emilia Maria Cristina Mazza
    • , Enrico Lugli
    • , Giacomo Cavalli
    •  & Francesco Ferrari