Functional genomics

  • Article
    | Open Access

    A difference in the survival of respiratory chain complex III deficient Bcs1lp.S78G mice was observed between two congenic mouse strains. Here the authors show how in one of the strains the combined effects of a spontaneously arising non-pathogenic variant and the disease-causing Bcs1lp.S78G mutation exacerbate CIII deficiency and disease progression.

    • Janne Purhonen
    • , Vladislav Grigorjev
    • , Robert Ekiert
    • , Noora Aho
    • , Jayasimman Rajendran
    • , Rafał Pietras
    • , Katarina Truvé
    • , Mårten Wikström
    • , Vivek Sharma
    • , Artur Osyczka
    • , Vineta Fellman
    •  & Jukka Kallijärvi
  • 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

    PALB2 is an established breast cancer risk gene but the pathogenicity of many variants remains uncharacterised. Here, the authors present a cDNA-based system for the functional analysis of PALB2 variants of unknown significance.

    • Rick A. C. M. Boonen
    • , Amélie Rodrigue
    • , Chantal Stoepker
    • , Wouter W. Wiegant
    • , Bas Vroling
    • , Milan Sharma
    • , Magdalena B. Rother
    • , Nandi Celosse
    • , Maaike P. G. Vreeswijk
    • , Fergus Couch
    • , Jacques Simard
    • , Peter Devilee
    • , Jean-Yves Masson
    •  & Haico van Attikum
  • Article
    | Open Access

    Most reagents designed to deliver cargo into cells are cationic and so cannot deliver cationic cargo. Here the authors show that pretreating cells with the anionic polymer poly(propylacrylic acid) facilitates the uptake and endosomal escape of a wide variety of cationic cargo in numerous cell types.

    • Brian C. Evans
    • , R. Brock Fletcher
    • , Kameron V. Kilchrist
    • , Eric A. Dailing
    • , Alvin J. Mukalel
    • , Juan M. Colazo
    • , Matthew Oliver
    • , Joyce Cheung-Flynn
    • , Colleen M. Brophy
    • , John W. Tierney
    • , Jeffrey S. Isenberg
    • , Kurt D. Hankenson
    • , Kedar Ghimire
    • , Cynthia Lander
    • , Charles A. Gersbach
    •  & Craig L. Duvall
  • 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

    Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

    • Elena López-Isac
    • , Marialbert Acosta-Herrera
    • , Martin Kerick
    • , Shervin Assassi
    • , Ansuman T. Satpathy
    • , Jeffrey Granja
    • , Maxwell R. Mumbach
    • , Lorenzo Beretta
    • , Carmen P. Simeón
    • , Patricia Carreira
    • , Norberto Ortego-Centeno
    • , Ivan Castellvi
    • , Lara Bossini-Castillo
    • , F. David Carmona
    • , Gisela Orozco
    • , Nicolas Hunzelmann
    • , Jörg H. W. Distler
    • , Andre Franke
    • , Claudio Lunardi
    • , Gianluca Moroncini
    • , Armando Gabrielli
    • , Jeska de Vries-Bouwstra
    • , Cisca Wijmenga
    • , Bobby P. C. Koeleman
    • , Annika Nordin
    • , Leonid Padyukov
    • , Anna-Maria Hoffmann-Vold
    • , Benedicte Lie
    • , R. Ríos
    • , J. L. Callejas
    • , J. A. Vargas-Hitos
    • , R. García-Portales
    • , M. T. Camps
    • , A. Fernández-Nebro
    • , M. F. González-Escribano
    • , F. J. García-Hernández
    • , M. J. Castillo
    • , M. A. Aguirre
    • , I. Gómez-Gracia
    • , B. Fernández-Gutiérrez
    • , L. Rodríguez-Rodríguez
    • , P. García de la Peña
    • , E. Vicente
    • , J. L. Andreu
    • , M Fernández de Castro
    • , F. J. López-Longo
    • , L. Martínez
    • , Fonollosa V
    • , A. Guillén
    • , G. Espinosa
    • , C. Tolosa
    • , A. Pros
    • , M. Rodríguez-Carballeira
    • , F. J. Narváez
    • , M. Rubio-Rivas
    • , Ortiz-Santamaría V
    • , A. B. Madroñero
    • , M. A. González-Gay
    • , B. Díaz
    • , L. Trapiella
    • , A. Sousa
    • , M. V. Egurbide
    • , P. Fanlo-Mateo
    • , L. Sáez-Comet
    • , F. Díaz
    • , Hernández V
    • , E. Beltrán
    • , J. A. Román-Ivorra
    • , E. Grau
    • , J. J. Alegre-Sancho
    • , M. Freire
    • , F. J. Blanco-García
    • , N. Oreiro
    • , T. Witte
    • , A. Kreuter
    • , G. Riemekasten
    • , P. Airó
    • , C. Magro
    • , A. E. Voskuyl
    • , M. C. Vonk
    • , R. Hesselstrand
    • , Susanna Proudman
    • , Wendy Stevens
    • , Mandana Nikpour
    • , J. Zochling
    • , J. Sahhar
    • , J. Roddy
    • , P. Nash
    • , K. Tymms
    • , M. Rischmueller
    • , S. Lester
    • , Timothy Vyse
    • , Ariane L. Herrick
    • , Jane Worthington
    • , Christopher P. Denton
    • , Yannick Allanore
    • , Matthew A. Brown
    • , Timothy R. D. J. Radstake
    • , Carmen Fonseca
    • , Howard Y. Chang
    • , Maureen D. Mayes
    •  & Javier Martin
  • Article
    | Open Access

    The synthesis of nanoparticles capable of orthogonal photo-activity is complex. Here, the authors report on an assembly process of two distinct nanoparticles into composite nanoparticles as a simple method and report on the application in photodynamic therapy and siRNA delivery in tumour therapy.

    • Zhen Zhang
    • , Muthu Kumara Gnanasammandhan Jayakumar
    • , Xiang Zheng
    • , Swati Shikha
    • , Yi Zhang
    • , Akshaya Bansal
    • , Dennis J. J. Poon
    • , Pek Lim Chu
    • , Eugenia L. L. Yeo
    • , Melvin L. K. Chua
    • , Soo Khee Chee
    •  & Yong Zhang
  • Article
    | Open Access

    Trans-homolog interactions, such as homolog pairing, are highly structured and associated with gene function in Drosophila cells. Here, the authors use haplotype-resolved Hi-C to identify genome-wide trans-homolog interactions in a Drosophila hybrid cell line and investigate their patterns and functional roles.

    • Jumana AlHaj Abed
    • , Jelena Erceg
    • , Anton Goloborodko
    • , Son C. Nguyen
    • , Ruth B. McCole
    • , Wren Saylor
    • , Geoffrey Fudenberg
    • , Bryan R. Lajoie
    • , Job Dekker
    • , Leonid A. Mirny
    •  & C.-ting Wu
  • Article
    | Open Access

    In plants, 3′ Pol II pausing helps prevent transcriptional interference. Here the authors provide evidence that BORDER proteins are enriched in intergenic regions and inhibit transcriptional interference between closely spaced genes by preventing RNA polymerase from intruding into the promoters of nearby downstream genes.

    • Xuhong Yu
    • , Pascal G. P. Martin
    •  & Scott D. Michaels
  • Article
    | Open Access

    HiChIP/PLAC-seq assay is popular for profiling 3D genome interactions among regulatory elements at kilobase resolution. Here the authors describe FitHiChIP an empirical null-based, flexible computational method for statistical significance estimation and loop calling from HiChIP data.

    • Sourya Bhattacharyya
    • , Vivek Chandra
    • , Pandurangan Vijayanand
    •  & Ferhat Ay
  • Article
    | Open Access

    Inversions are a little-studied type of genomic variation that could contribute to phenotypic traits. Here the authors characterize 45 common polymorphic inversions in human populations and investigate their evolutionary and functional impact.

    • Carla Giner-Delgado
    • , Sergi Villatoro
    • , Jon Lerga-Jaso
    • , Magdalena Gayà-Vidal
    • , Meritxell Oliva
    • , David Castellano
    • , Lorena Pantano
    • , Bárbara D. Bitarello
    • , David Izquierdo
    • , Isaac Noguera
    • , Iñigo Olalde
    • , Alejandra Delprat
    • , Antoine Blancher
    • , Carles Lalueza-Fox
    • , Tõnu Esko
    • , Paul F. O’Reilly
    • , Aida M. Andrés
    • , Luca Ferretti
    • , Marta Puig
    •  & Mario Cáceres
  • Article
    | Open Access

    Epistasis underlies the complexity of genotype-phenotype maps. Here, the authors analyze 8,192 mutants that link two phenotypically distinct variants of the Entacmaea quadricolor fluorescent protein, and show the existence, but also the sparsity, of high-order epistatic interactions.

    • Frank J. Poelwijk
    • , Michael Socolich
    •  & Rama Ranganathan
  • Article
    | Open Access

    Although many neuropsychiatric risk genes are known to contribute to epigenetic regulation of gene expression, very little is known about specific chromatin-associated mechanisms that govern the formation and maintenance of neuronal connectivity. Here, the authors report that transcallosal connectivity is critically dependent on C11orf46/ARL14EP, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus, and that RNA-guided epigenetic editing of hyperexpressed Sema6a gene promoters in C11orf46-knockdown neurons resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling.

    • Cyril J. Peter
    • , Atsushi Saito
    • , Yuto Hasegawa
    • , Yuya Tanaka
    • , Mohika Nagpal
    • , Gabriel Perez
    • , Emily Alway
    • , Sergio Espeso-Gil
    • , Tariq Fayyad
    • , Chana Ratner
    • , Aslihan Dincer
    • , Achla Gupta
    • , Lakshmi Devi
    • , John G. Pappas
    • , François M. Lalonde
    • , John A. Butman
    • , Joan C. Han
    • , Schahram Akbarian
    •  & Atsushi Kamiya
  • Article
    | Open Access

    Off-target effects in CRISPR screens for essential regulatory elements have not been systematically evaluated. Here the authors find Cas9 nuclease, CRISPRi/a each have distinct off-target effects, and that these can be accurately identified and removed using the GuideScan sgRNA specificity score.

    • Josh Tycko
    • , Michael Wainberg
    • , Georgi K. Marinov
    • , Oana Ursu
    • , Gaelen T. Hess
    • , Braeden K. Ego
    • , Aradhana
    • , Amy Li
    • , Alisa Truong
    • , Alexandro E. Trevino
    • , Kaitlyn Spees
    • , David Yao
    • , Irene M. Kaplow
    • , Peyton G. Greenside
    • , David W. Morgens
    • , Douglas H. Phanstiel
    • , Michael P. Snyder
    • , Lacramioara Bintu
    • , William J. Greenleaf
    • , Anshul Kundaje
    •  & Michael C. Bassik
  • Article
    | Open Access

    Non-additive genetic interactions are plastic and can complicate genetic prediction. Here, using deep mutagenesis of the lambda repressor, Li et al. reveal that changes in gene expression can alter the strength and direction of genetic interactions between mutations in many genes and develop mathematical models for predicting them.

    • Xianghua Li
    • , Jasna Lalić
    • , Pablo Baeza-Centurion
    • , Riddhiman Dhar
    •  & Ben Lehner
  • Article
    | Open Access

    DICER is involved in the processing of miRNAs, where the RNase IIIa and IIIb domains are thought to cut the 3p and 5p hairpin arms, respectively. Here, in endometrial cancer, the authors identify an RNase IIIa mutation, which phenocopies mutations in the RNase IIIb domain.

    • Jeffrey Vedanayagam
    • , Walid K. Chatila
    • , Bülent Arman Aksoy
    • , Sonali Majumdar
    • , Anders Jacobsen Skanderup
    • , Emek Demir
    • , Nikolaus Schultz
    • , Chris Sander
    •  & Eric C. Lai
  • Article
    | Open Access

    Studying how genetic variants in different genes interact and their combinatorial output is experimentally and analytically challenging. Here, the authors quantify the effects of more than 5000 mutation pairs in the yeast GAL regulatory system, finding that many combinations can be predicted with statistical models.

    • Aaron M. New
    •  & Ben Lehner
  • 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

    Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

    • Andrew D. Johnston
    • , Claudia A. Simões-Pires
    • , Taylor V. Thompson
    • , Masako Suzuki
    •  & John M. Greally
  • Article
    | Open Access

    The position, shape and number of transcription start sites (TSS) regulate gene expression. Here authors present MAPCap, a method for high-resolution detection and differential expression analysis of TSS, and apply MAPCap to early fly development, detecting stage and sex-specific promoter and enhancer activity.

    • Vivek Bhardwaj
    • , Giuseppe Semplicio
    • , Niyazi Umut Erdogdu
    • , Thomas Manke
    •  & Asifa Akhtar
  • Article
    | Open Access

    The role of mitochondrial DNA mutations in organismal fitness and lifespan have been studied in mitochondrial mutator models with varying results. Here, the authors generate a new APOBEC1 expression-based Drosophila mutator model and show that it has limited mitochondrial function and reduced lifespan.

    • Simonetta Andreazza
    • , Colby L. Samstag
    • , Alvaro Sanchez-Martinez
    • , Erika Fernandez-Vizarra
    • , Aurora Gomez-Duran
    • , Juliette J. Lee
    • , Roberta Tufi
    • , Michael J. Hipp
    • , Elizabeth K. Schmidt
    • , Thomas J. Nicholls
    • , Payam A. Gammage
    • , Patrick F. Chinnery
    • , Michal Minczuk
    • , Leo J. Pallanck
    • , Scott R. Kennedy
    •  & Alexander J. Whitworth
  • 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

    GWAS have identified risk loci for osteoarthritis (OA), but the causal variants still have to be determined. Here, the authors apply a massively-parallel reporter assay to screen 1,605 candidate SNPs in 35 OA loci, which prioritizes six SNPs in four loci, one of which, rs4730222, is characterized in more detail.

    • Jason C. Klein
    • , Aidan Keith
    • , Sarah J. Rice
    • , Colin Shepherd
    • , Vikram Agarwal
    • , John Loughlin
    •  & Jay Shendure
  • Article
    | Open Access

    Gene fusions are observed in many cancers but their link to tumour fitness is largely unknown. Here, transcriptomic analysis combined with pharmacological and CRISPR-Cas9 screening of cancer cell lines was used to evaluate the functional linkage between fusions and tumour fitness.

    • Gabriele Picco
    • , Elisabeth D. Chen
    • , Luz Garcia Alonso
    • , Fiona M. Behan
    • , Emanuel Gonçalves
    • , Graham Bignell
    • , Angela Matchan
    • , Beiyuan Fu
    • , Ruby Banerjee
    • , Elizabeth Anderson
    • , Adam Butler
    • , Cyril H. Benes
    • , Ultan McDermott
    • , David Dow
    • , Francesco Iorio
    • , Euan Stronach
    • , Fengtang Yang
    • , Kosuke Yusa
    • , Julio Saez-Rodriguez
    •  & Mathew J. Garnett
  • Article
    | Open Access

    Systemic lupus erythematosus (SLE) shows a striking bias towards higher prevalence in females. Here, the authors perform fine-mapping of an SLE-associated locus at Xp21.2 and characterise a candidate gene, CXorf21, as IFN-responsive in immune cells that shows sexually dimorphic expression.

    • Christopher A. Odhams
    • , Amy L. Roberts
    • , Susan K. Vester
    • , Carolina S. T. Duarte
    • , Charlie T. Beales
    • , Alexander J. Clarke
    • , Sonja Lindinger
    • , Samuel J. Daffern
    • , Antonino Zito
    • , Lingyan Chen
    • , Leonardo L. Jones
    • , Lora Boteva
    • , David L. Morris
    • , Kerrin S. Small
    • , Michelle M. A. Fernando
    • , Deborah S. Cunninghame Graham
    •  & Timothy J. Vyse
  • Article
    | Open Access

    GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

    • Alessandra Chesi
    • , Yadav Wagley
    • , Matthew E. Johnson
    • , Elisabetta Manduchi
    • , Chun Su
    • , Sumei Lu
    • , Michelle E. Leonard
    • , Kenyaita M. Hodge
    • , James A. Pippin
    • , Kurt D. Hankenson
    • , Andrew D. Wells
    •  & Struan F. A. Grant
  • Article
    | Open Access

    GWAS have identified over 41 susceptibility loci for Parkinson’s disease (PD). Here, the authors integrate PD GWAS summary statistics with transcriptome data from monocytes and DLFPC tissue in a TWAS approach and find 66 significant associations with PD risk highlighting lysosomal and innate immune functions.

    • Yang I. Li
    • , Garrett Wong
    • , Jack Humphrey
    •  & Towfique Raj
  • Article
    | Open Access

    Autophagic activity decreases with age via unknown mechanisms. Here the authors show that expression of the negative autophagy regulator Rubicon increases with age, that its genetic ablation improves lifespan and ameliorates a number of age-associated phenotypes in invertebrates and in mouse models.

    • Shuhei Nakamura
    • , Masaki Oba
    • , Mari Suzuki
    • , Atsushi Takahashi
    • , Tadashi Yamamuro
    • , Mari Fujiwara
    • , Kensuke Ikenaka
    • , Satoshi Minami
    • , Namine Tabata
    • , Kenichi Yamamoto
    • , Sayaka Kubo
    • , Ayaka Tokumura
    • , Kanako Akamatsu
    • , Yumi Miyazaki
    • , Tsuyoshi Kawabata
    • , Maho Hamasaki
    • , Koji Fukui
    • , Kazunori Sango
    • , Yoshihisa Watanabe
    • , Yoshitsugu Takabatake
    • , Tomoya S. Kitajima
    • , Yukinori Okada
    • , Hideki Mochizuki
    • , Yoshitaka Isaka
    • , Adam Antebi
    •  & Tamotsu Yoshimori
  • Article
    | Open Access

    PIWI-interacting RNAs (piRNAs) are regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity. Here the authors characterized their binding specificity and reveal the 5′ nucleotide bias of the Drosophila Piwi protein, through mutation of its specificity loop.

    • Chad B. Stein
    • , Pavol Genzor
    • , Sanga Mitra
    • , Alexandra R. Elchert
    • , Jonathan J. Ipsaro
    • , Leif Benner
    • , Sushil Sobti
    • , Yijun Su
    • , Molly Hammell
    • , Leemor Joshua-Tor
    •  & Astrid D. Haase
  • Article
    | Open Access

    AGO2 is a core component of the RNAi machinery and contributes to plant immunity during bacterial infection. Here the authors show that AGO2 activity is suppressed by arginine methylation which not only promotes AGO2 degradation but also recruits TSN proteins to degrade AGO2-associated small RNAs.

    • Po Hu
    • , Hongwei Zhao
    • , Pei Zhu
    • , Yongsheng Xiao
    • , Weili Miao
    • , Yinsheng Wang
    •  & Hailing Jin
  • Article
    | Open Access

    We know a large number of risk SNPs for schizophrenia, but little about how these SNPs contribute to the disorder. Here, the authors use functional genomics to identify risk SNPs that disrupt transcription factor binding and validate the regulatory effects of the transcription factor binding-disrupting SNPs.

    • Yongxia Huo
    • , Shiwu Li
    • , Jiewei Liu
    • , Xiaoyan Li
    •  & Xiong-Jian Luo
  • Article
    | Open Access

    Most cyanobacteria are oxygenic photoautotrophs, and fermenters under dark anoxic conditions. Here, the authors analyse genomic sequences of related uncultivated bacteria, inferring their metabolic potential, and supporting that their common ancestor was an anaerobe capable of fermentation and H2 metabolism.

    • Paula B. Matheus Carnevali
    • , Frederik Schulz
    • , Cindy J. Castelle
    • , Rose S. Kantor
    • , Patrick M. Shih
    • , Itai Sharon
    • , Joanne M. Santini
    • , Matthew R. Olm
    • , Yuki Amano
    • , Brian C. Thomas
    • , Karthik Anantharaman
    • , David Burstein
    • , Eric D. Becraft
    • , Ramunas Stepanauskas
    • , Tanja Woyke
    •  & Jillian F. Banfield
  • Article
    | Open Access

    The Pacific white shrimp Litopenaeus vannamei is an important aquaculture species and a promising model for crustacean biology. Here, the authors provide a reference genome assembly, and show that gene expansion is involved in the regulation of frequent molting as well as benthic adaptation of the shrimp.

    • Xiaojun Zhang
    • , Jianbo Yuan
    • , Yamin Sun
    • , Shihao Li
    • , Yi Gao
    • , Yang Yu
    • , Chengzhang Liu
    • , Quanchao Wang
    • , Xinjia Lv
    • , Xiaoxi Zhang
    • , Ka Yan Ma
    • , Xiaobo Wang
    • , Wenchao Lin
    • , Long Wang
    • , Xueli Zhu
    • , Chengsong Zhang
    • , Jiquan Zhang
    • , Songjun Jin
    • , Kuijie Yu
    • , Jie Kong
    • , Peng Xu
    • , Jack Chen
    • , Hongbin Zhang
    • , Patrick Sorgeloos
    • , Amir Sagi
    • , Acacia Alcivar-Warren
    • , Zhanjiang Liu
    • , Lei Wang
    • , Jue Ruan
    • , Ka Hou Chu
    • , Bin Liu
    • , Fuhua Li
    •  & Jianhai Xiang
  • Article
    | Open Access

    Gain of function methods based on gene overexpression are not easily applied to high-throughput screening across different experimental conditions. Here, the authors present Dub-seq, which separates overexpression library characterization from functional screening and uses random DNA barcodes to increase the experimental throughput.

    • Vivek K. Mutalik
    • , Pavel S. Novichkov
    • , Morgan N. Price
    • , Trenton K. Owens
    • , Mark Callaghan
    • , Sean Carim
    • , Adam M. Deutschbauer
    •  & Adam P. Arkin
  • Article
    | Open Access

    Millions of enhancers are predicted, but their validation remains challenging. Here, the authors report genome-wide enhancer function quantification and high-resolution dissection for millions of accessible DNA fragments, revealing driver nucleotides and helping interpret non-coding disease variants.

    • Xinchen Wang
    • , Liang He
    • , Sarah M. Goggin
    • , Alham Saadat
    • , Li Wang
    • , Nasa Sinnott-Armstrong
    • , Melina Claussnitzer
    •  & Manolis Kellis
  • Article
    | Open Access

    Increasing insecticide resistance of mosquitoes represents a public health threat, and underlying mechanisms are poorly understood. Here, Ingham et al. identify putative insecticide resistance genes in Anopheles gambiae populations across Africa and develop a web-based application that maps their expression.

    • V. A. Ingham
    • , S. Wagstaff
    •  & H. Ranson
  • Review Article
    | Open Access

    In this review, Aravin and colleagues examine bacterial and archaeal Argonaute proteins, discuss their diverse architectures and their possible roles in host defense, proposing additional functions for Argonaute proteins in prokaryotic cells.

    • Lidiya Lisitskaya
    • , Alexei A. Aravin
    •  & Andrey Kulbachinskiy
  • Article
    | Open Access

    A small RNA-based signaling cascade prevents the induction of plant resistance genes (R-genes) in the absence of pathogen challenge. Here Cai et al. show that nuclear accumulation of the R protein SNC1 can activate immunity by suppressing small RNA production and releasing R-gene repression.

    • Qiang Cai
    • , Chao Liang
    • , Suikang Wang
    • , Yingnan Hou
    • , Lei Gao
    • , Li Liu
    • , Wenrong He
    • , Wenbo Ma
    • , Beixin Mo
    •  & Xuemei Chen
  • Article
    | Open Access

    Topoisomerases solve topological problems during DNA metabolism, but their role in RNA metabolism remains unclear. Here the authors provide evidence that in Drosophila, Topoisomerase 3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) to promote heterochromatin formation and transcriptional silencing.

    • Seung Kyu Lee
    • , Yutong Xue
    • , Weiping Shen
    • , Yongqing Zhang
    • , Yuyoung Joo
    • , Muzammil Ahmad
    • , Madoka Chinen
    • , Yi Ding
    • , Wai Lim Ku
    • , Supriyo De
    • , Elin Lehrmann
    • , Kevin G. Becker
    • , Elissa P. Lei
    • , Keji Zhao
    • , Sige Zou
    • , Alexei Sharov
    •  & Weidong Wang
  • 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
    • , Jayadeva
    •  & Debarka Sengupta
  • Article
    | Open Access

    Small interfering (siRNAs) can be toxic to cancer cells. Here the authors investigate the toxicity of microRNA in cancer cells by performing a siRNA screen that tests the miRNA activities of an extensive list of miRNAs with different 6mer seed sequences.

    • Quan Q. Gao
    • , William E. Putzbach
    • , Andrea E. Murmann
    • , Siquan Chen
    • , Aishe A. Sarshad
    • , Johannes M. Peter
    • , Elizabeth T. Bartom
    • , Markus Hafner
    •  & Marcus E. Peter
  • Article
    | Open Access

    CTCF mediates long-range chromatin interactions which are important for genome organization and function. Here, the authors demonstrate that CTCF-mediated interactome exhibits extensive plasticity and present Lollipop, a machine-learning framework which predicts CTCF-mediated long-range interactions using genomic and epigenomic features.

    • Yan Kai
    • , Jaclyn Andricovich
    • , Zhouhao Zeng
    • , Jun Zhu
    • , Alexandros Tzatsos
    •  & Weiqun Peng
  • Article
    | Open Access

    Mutations often show distinct phenotypic effects across different genetic backgrounds. Here the authors describe the genetic basis of these so-called background effects using data on genotype and growth in 10 environments from 1411 segregants from a cross of two strains of budding yeast.

    • Martin N. Mullis
    • , Takeshi Matsui
    • , Rachel Schell
    • , Ryan Foree
    •  & Ian M. Ehrenreich
  • Article
    | Open Access

    Depletion of the splicing factors MBNL 1 and 2 causes myotonic dystrophy. Here, the authors show that miR-23b and miR-218 target MBNL proteins, and that antagonists to these miRNAs rescue mis-splicing events in myoblasts and boost MBNL expression and rescue pathology in mouse models.

    • Estefania Cerro-Herreros
    • , Maria Sabater-Arcis
    • , Juan M. Fernandez-Costa
    • , Nerea Moreno
    • , Manuel Perez-Alonso
    • , Beatriz Llamusi
    •  & Ruben Artero
  • Article
    | Open Access

    Systemic investigation of the bacterial genome is essential for both basic microbiology and bioengineering. Here the authors demonstrate CRISPRi pooled screening as a high-throughput tool for identifying gene and phenotype associations in bacteria.

    • Tianmin Wang
    • , Changge Guan
    • , Jiahui Guo
    • , Bing Liu
    • , Yinan Wu
    • , Zhen Xie
    • , Chong Zhang
    •  & Xin-Hui Xing
  • Article
    | Open Access

    Temporal programs of genome replication show different levels of conservation between closely or distantly related species. Here, the authors generate genome-wide replication timing profiles for ten yeast species, and analyze their evolutionary dynamics.

    • Nicolas Agier
    • , Stéphane Delmas
    • , Qing Zhang
    • , Aubin Fleiss
    • , Yan Jaszczyszyn
    • , Erwin van Dijk
    • , Claude Thermes
    • , Martin Weigt
    • , Marco Cosentino-Lagomarsino
    •  & Gilles Fischer
  • Article
    | Open Access

    Systematic analysis of the control of dynamic cellular processes remains a challenge. Here the authors introduce a pipeline enabling them to identify TFs involved in Src-induced cellular transformation, and find that a large number of TFs with diverse DNA binding specificities orchestrate the process.

    • Zhe Ji
    • , Lizhi He
    • , Asaf Rotem
    • , Andreas Janzer
    • , Christine S. Cheng
    • , Aviv Regev
    •  & Kevin Struhl
  • Article
    | Open Access

    The SCRaMbLE system integrated into Sc2.0’s synthetic yeast chromosome project allows rapid strain evolution. Here the authors use a genetic logic gate to control induction of recombination in a haploid and diploid yeast carrying synthetic chromosomes.

    • Bin Jia
    • , Yi Wu
    • , Bing-Zhi Li
    • , Leslie A. Mitchell
    • , Hong Liu
    • , Shuo Pan
    • , Juan Wang
    • , Hao-Ran Zhang
    • , Nan Jia
    • , Bo Li
    • , Michael Shen
    • , Ze-Xiong Xie
    • , Duo Liu
    • , Ying-Xiu Cao
    • , Xia Li
    • , Xiao Zhou
    • , Hao Qi
    • , Jef D. Boeke
    •  & Ying-Jin Yuan