Computational biology and bioinformatics

  • Article
    | Open Access

    Previous study identified in vivo structured mRNA regions in Saccharomyces cerevisiae by dimethyl sulfate-sequencing. Here the authors use quantitative proteomics to identify protein interactors of 186 RNA folds in S. cerevisiae, providing functional links between RNA binding proteins and distinct mRNA fold.

    • Nuria Casas-Vila
    • , Sergi Sayols
    • , Lara Pérez-Martínez
    • , Marion Scheibe
    •  & Falk Butter
  • Article
    | Open Access

    Seasonal influenza epidemics vary in timing and size, but the causes of the variation remain unclear. Here, the authors analyse a 15-year city-level data set, and find that fluctuations in climatic factors do not predict onset timing, and that while antigenic change does not have a consistent effect on epidemic size, the timing of onset and heterosubtypic competition do.

    • Edward K. S. Lam
    • , Dylan H. Morris
    • , Aeron C. Hurt
    • , Ian G. Barr
    •  & Colin A. Russell
  • Article
    | Open Access

    Identification of genes that determine and regulate cell identity remains challenging. Here, the authors use machine learning to identify cell identity genes and master regulator transcription factors based on gene expression profiles and histone modifications.

    • Bo Xia
    • , Dongyu Zhao
    • , Guangyu Wang
    • , Min Zhang
    • , Jie Lv
    • , Alin S. Tomoiaga
    • , Yanqiang Li
    • , Xin Wang
    • , Shu Meng
    • , John P. Cooke
    • , Qi Cao
    • , Lili Zhang
    •  & Kaifu Chen
  • Article
    | Open Access

    Sample index hopping results in various artefacts in multiplexed scRNA-seq experiments. Here, the authors introduce a statistical model to estimate sample index hopping rate in droplet-based scRNA-seq data and show that artifacts can be corrected by purging phantom molecules from the data.

    • Rick Farouni
    • , Haig Djambazian
    • , Lorenzo E. Ferri
    • , Jiannis Ragoussis
    •  & Hamed S. Najafabadi
  • Article
    | Open Access

    Phosphorylation plays an important role in the regulation of molecular circadian clocks. Here the authors utilize multi-omics data from flies to describe the circadian kinome and identify GASKET as a potentially important regulator within the circadian kinase network.

    • Chenwei Wang
    • , Ke Shui
    • , Shanshan Ma
    • , Shaofeng Lin
    • , Ying Zhang
    • , Bo Wen
    • , Wankun Deng
    • , Haodong Xu
    • , Hui Hu
    • , Anyuan Guo
    • , Yu Xue
    •  & Luoying Zhang
  • Article
    | Open Access

    Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

    • Nicola Whiffin
    • , Konrad J. Karczewski
    • , Xiaolei Zhang
    • , Sonia Chothani
    • , Miriam J. Smith
    • , D. Gareth Evans
    • , Angharad M. Roberts
    • , Nicholas M. Quaife
    • , Sebastian Schafer
    • , Owen Rackham
    • , Jessica Alföldi
    • , Anne H. O’Donnell-Luria
    • , Laurent C. Francioli
    • , Irina M. Armean
    • , Eric Banks
    • , Louis Bergelson
    • , Kristian Cibulskis
    • , Ryan L. Collins
    • , Kristen M. Connolly
    • , Miguel Covarrubias
    • , Beryl Cummings
    • , Mark J. Daly
    • , Stacey Donnelly
    • , Yossi Farjoun
    • , Steven Ferriera
    • , Stacey Gabriel
    • , Laura D. Gauthier
    • , Jeff Gentry
    • , Namrata Gupta
    • , Thibault Jeandet
    • , Diane Kaplan
    • , Kristen M. Laricchia
    • , Christopher Llanwarne
    • , Eric V. Minikel
    • , Ruchi Munshi
    • , Benjamin M. Neale
    • , Sam Novod
    • , Nikelle Petrillo
    • , Timothy Poterba
    • , David Roazen
    • , Valentin Ruano-Rubio
    • , Andrea Saltzman
    • , Kaitlin E. Samocha
    • , Molly Schleicher
    • , Cotton Seed
    • , Matthew Solomonson
    • , Jose Soto
    • , Grace Tiao
    • , Kathleen Tibbetts
    • , Charlotte Tolonen
    • , Christopher Vittal
    • , Gordon Wade
    • , Arcturus Wang
    • , Qingbo Wang
    • , Nicholas A. Watts
    • , Ben Weisburd
    • , Carlos A. Aguilar Salinas
    • , Tariq Ahmad
    • , Christine M. Albert
    • , Diego Ardissino
    • , Gil Atzmon
    • , John Barnard
    • , Laurent Beaugerie
    • , Emelia J. Benjamin
    • , Michael Boehnke
    • , Lori L. Bonnycastle
    • , Erwin P. Bottinger
    • , Donald W. Bowden
    • , Matthew J. Bown
    • , John C. Chambers
    • , Juliana C. Chan
    • , Daniel Chasman
    • , Judy Cho
    • , Mina K. Chung
    • , Bruce Cohen
    • , Adolfo Correa
    • , Dana Dabelea
    • , Mark J. Daly
    • , Dawood Darbar
    • , Ravindranath Duggirala
    • , Josée Dupuis
    • , Patrick T. Ellinor
    • , Roberto Elosua
    • , Jeanette Erdmann
    • , Tõnu Esko
    • , Martti Färkkilä
    • , Jose Florez
    • , Andre Franke
    • , Gad Getz
    • , Benjamin Glaser
    • , Stephen J. Glatt
    • , David Goldstein
    • , Clicerio Gonzalez
    • , Leif Groop
    • , Christopher Haiman
    • , Craig Hanis
    • , Matthew Harms
    • , Mikko Hiltunen
    • , Matti M. Holi
    • , Christina M. Hultman
    • , Mikko Kallela
    • , Jaakko Kaprio
    • , Sekar Kathiresan
    • , Bong-Jo Kim
    • , Young Jin Kim
    • , George Kirov
    • , Jaspal Kooner
    • , Seppo Koskinen
    • , Harlan M. Krumholz
    • , Subra Kugathasan
    • , Soo Heon Kwak
    • , Markku Laakso
    • , Terho Lehtimäki
    • , Ruth J. F. Loos
    • , Steven A. Lubitz
    • , Ronald C. W. Ma
    • , Jaume Marrugat
    • , Kari M. Mattila
    • , Steven McCarroll
    • , Mark I. McCarthy
    • , Dermot McGovern
    • , Ruth McPherson
    • , James B. Meigs
    • , Olle Melander
    • , Andres Metspalu
    • , Benjamin M. Neale
    • , Peter M. Nilsson
    • , Michael C. O’Donovan
    • , Dost Ongur
    • , Lorena Orozco
    • , Michael J. Owen
    • , Colin N. A. Palmer
    • , Aarno Palotie
    • , Kyong Soo Park
    • , Carlos Pato
    • , Ann E. Pulver
    • , Nazneen Rahman
    • , Anne M. Remes
    • , John D. Rioux
    • , Samuli Ripatti
    • , Dan M. Roden
    • , Danish Saleheen
    • , Veikko Salomaa
    • , Nilesh J. Samani
    • , Jeremiah Scharf
    • , Heribert Schunkert
    • , Moore B. Shoemaker
    • , Pamela Sklar
    • , Hilkka Soininen
    • , Harry Sokol
    • , Tim Spector
    • , Patrick F. Sullivan
    • , Jaana Suvisaari
    • , E. Shyong Tai
    • , Yik Ying Teo
    • , Tuomi Tiinamaija
    • , Ming Tsuang
    • , Dan Turner
    • , Teresa Tusie-Luna
    • , Erkki Vartiainen
    • , Hugh Watkins
    • , Rinse K. Weersma
    • , Maija Wessman
    • , James G. Wilson
    • , Ramnik J. Xavier
    • , Stuart A. Cook
    • , Paul J. R. Barton
    • , Daniel G. MacArthur
    •  & James S. Ware
  • Article
    | Open Access

    It is crucial yet challenging to identify cause-consequence relation in complex dynamical systems where direct causal links can mix with indirect ones. Leng et al. propose a data-driven model-independent method to distinguish direct from indirect causality and test its applicability to real-world data.

    • Siyang Leng
    • , Huanfei Ma
    • , Jürgen Kurths
    • , Ying-Cheng Lai
    • , Wei Lin
    • , Kazuyuki Aihara
    •  & Luonan Chen
  • Article
    | Open Access

    Regulation of chromosome structure plays essential roles in many nuclear processes. Here, the authors present TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci and find that during gene activation, transcription starting sites contact with open chromatin regions into active physical domains.

    • Marco Di Stefano
    • , Ralph Stadhouders
    • , Irene Farabella
    • , David Castillo
    • , François Serra
    • , Thomas Graf
    •  & Marc A. Marti-Renom
  • Article
    | Open Access

    The association between leguminous plants and rhizobial bacteria is a paradigmatic example of a symbiosis driven by metabolic exchanges. Here, diCenzo et al. report the reconstruction and modelling of a genome-scale metabolic network of the plant Medicago truncatula nodulated by the bacterium Sinorhizobium meliloti.

    • George C. diCenzo
    • , Michelangelo Tesi
    • , Thomas Pfau
    • , Alessio Mengoni
    •  & Marco Fondi
  • Article
    | Open Access

    Multicellularity is one of the major transitions in evolution. Here, authors use a model to show that compared to unicellular bacteria, multicellular fungi can more rapidly colonise immobile, nutrient poor resources because exoenzymes provide greater or longer lasting benefits to mycelial organisms.

    • Luke L. M. Heaton
    • , Nick S. Jones
    •  & Mark D. Fricker
  • Article
    | Open Access

    Sensory drive theory posits that selection on sexual signals should depend on the environmental background. Here, Hulse et al. analyze the spatial statistics of body patterning in 10 darter fish species and find a correlation with habitat spatial statistics only for males, consistent with sexual selection via sensory drive.

    • Samuel V. Hulse
    • , Julien P. Renoult
    •  & Tamra C. Mendelson
  • Article
    | Open Access

    Electronic Health Records (EHR) are subject to noise, biases and missing data. Here, the authors present MixEHR, a multi-view Bayesian framework related to collaborative filtering and latent topic models for EHR data integration and modeling.

    • Yue Li
    • , Pratheeksha Nair
    • , Xing Han Lu
    • , Zhi Wen
    • , Yuening Wang
    • , Amir Ardalan Kalantari Dehaghi
    • , Yan Miao
    • , Weiqi Liu
    • , Tamas Ordog
    • , Joanna M. Biernacka
    • , Euijung Ryu
    • , Janet E. Olson
    • , Mark A. Frye
    • , Aihua Liu
    • , Liming Guo
    • , Ariane Marelli
    • , Yuri Ahuja
    • , Jose Davila-Velderrain
    •  & Manolis Kellis
  • Article
    | Open Access

    The low curation of existing nanomaterials’s databases is limiting their application in modeling studies. Here the authors report a publicly available nanomaterial database that contains annotated nanostructures of diverse nanomaterials immediately available for modeling research studies.

    • Xiliang Yan
    • , Alexander Sedykh
    • , Wenyi Wang
    • , Bing Yan
    •  & Hao Zhu
  • Article
    | Open Access

    The increasing amount of sequenced microbial genomes and metagenomes requires platforms for efficient integrated analysis. Here, Asnicar et al. present PhyloPhlAn 3.0, a pipeline allowing large-scale microbial genome characterization and phylogenetic contextualization at multiple levels of resolution.

    • Francesco Asnicar
    • , Andrew Maltez Thomas
    • , Francesco Beghini
    • , Claudia Mengoni
    • , Serena Manara
    • , Paolo Manghi
    • , Qiyun Zhu
    • , Mattia Bolzan
    • , Fabio Cumbo
    • , Uyen May
    • , Jon G. Sanders
    • , Moreno Zolfo
    • , Evguenia Kopylova
    • , Edoardo Pasolli
    • , Rob Knight
    • , Siavash Mirarab
    • , Curtis Huttenhower
    •  & Nicola Segata
  • Article
    | Open Access

    Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

    • Katherine C. Goldfarbmuren
    • , Nathan D. Jackson
    • , Satria P. Sajuthi
    • , Nathan Dyjack
    • , Katie S. Li
    • , Cydney L. Rios
    • , Elizabeth G. Plender
    • , Michael T. Montgomery
    • , Jamie L. Everman
    • , Preston E. Bratcher
    • , Eszter K. Vladar
    •  & Max A. Seibold
  • Article
    | Open Access

    Genetic changes acquired during in vitro culture pose a challenge to application of stem cells. Here the authors use whole genome sequencing to show that cultured human adult and pluripotent stem cells have a high mutational load caused by oxidative stress and reduced oxygen tension in culture lowers mutation rates.

    • Ewart Kuijk
    • , Myrthe Jager
    • , Bastiaan van der Roest
    • , Mauro D. Locati
    • , Arne Van Hoeck
    • , Jerome Korzelius
    • , Roel Janssen
    • , Nicolle Besselink
    • , Sander Boymans
    • , Ruben van Boxtel
    •  & Edwin Cuppen
  • Article
    | Open Access

    Protospacer adjacent motif (PAM) requirements limit the target range of CRISPR endonucleases. Here, the authors graft the 5$$^{\prime}$$-NAAN-3$$^{\prime}$$ PAM-interacting domain of SmacCas9 onto SpyCas9 to create adenine dinucleotide targeting chimeras.

    • Pranam Chatterjee
    • , Jooyoung Lee
    • , Lisa Nip
    • , Sabrina R. T. Koseki
    • , Emma Tysinger
    • , Erik J. Sontheimer
    • , Joseph M. Jacobson
    •  & Noah Jakimo
  • Article
    | Open Access

    Characterization of the distance over which TF binding influences gene expression is important for inferring target genes. Here the authors study this relationship using thousands of genomic data sets, finding two classes of TFs with distinct ranges of regulatory influence modulated by chromatin states of topologically associated domains.

    • Chen-Hao Chen
    • , Rongbin Zheng
    • , Collin Tokheim
    • , Xin Dong
    • , Jingyu Fan
    • , Changxin Wan
    • , Qin Tang
    • , Myles Brown
    • , Jun S. Liu
    • , Clifford A. Meyer
    •  & X. Shirley Liu
  • Review Article
    | Open Access

    Our efforts to build complex synthetic biology circuits are impeded by limited knowledge of optimal combinations. In this review, the authors consider current combinatorial methods and look to emerging technologies.

    • Gita Naseri
    •  & Mattheos A. G. Koffas
  • Article
    | Open Access

    The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

    • Meera C. Viswanathan
    • , William Schmidt
    • , Peter Franz
    • , Michael J. Rynkiewicz
    • , Christopher S. Newhard
    • , Aditi Madan
    • , William Lehman
    • , Douglas M. Swank
    • , Matthias Preller
    •  & Anthony Cammarato
  • Article
    | Open Access

    Plasmids can mediate the exchange of genetic material between bacterial cells. Here, Acman et al. use network analyses to study the population structure and dynamics of over 10,000 plasmids, assigning them into cliques that correlate with gene content, host range, and existing classifications based on replicon and mobility types.

    • Mislav Acman
    • , Lucy van Dorp
    • , Joanne M. Santini
    •  & Francois Balloux
  • Article
    | Open Access

    Uveal melanoma has a propensity to metastasise. Here, the authors report the whole genome sequence of 103 uveal melanomas and find that the tumour mutational burden is variable and that two subsets of tumours are characterised by MBD4 mutations and a UV exposure signature.

    • Peter A. Johansson
    • , Kelly Brooks
    • , Felicity Newell
    • , Jane M. Palmer
    • , James S. Wilmott
    • , Antonia L. Pritchard
    • , Natasa Broit
    • , Scott Wood
    • , Matteo S. Carlino
    • , Conrad Leonard
    • , Lambros T. Koufariotis
    • , Vaishnavi Nathan
    • , Aaron B. Beasley
    • , Madeleine Howlie
    • , Rebecca Dawson
    • , Helen Rizos
    • , Chris W. Schmidt
    • , Georgina V. Long
    • , Hayley Hamilton
    • , Jens F. Kiilgaard
    • , Timothy Isaacs
    • , Elin S. Gray
    • , Olivia J. Rolfe
    • , John J. Park
    • , Andrew Stark
    • , Graham J. Mann
    • , Richard A. Scolyer
    • , John V. Pearson
    • , Nicolas van Baren
    • , Nicola Waddell
    • , Karin W. Wadt
    • , Lindsay A. McGrath
    • , Sunil K. Warrier
    • , William Glasson
    •  & Nicholas K. Hayward
  • Article
    | Open Access

    The TATA-box binding protein (TBP) is required for transcription initiation in archaea and eukaryotes. Here the authors delineate how TBP’s function has evolved new functional features through context-dependent interactions with various protein partners.

    • Charles N. J. Ravarani
    • , Tilman Flock
    • , Sreenivas Chavali
    • , Madhanagopal Anandapadamanaban
    • , M. Madan Babu
    •  & Santhanam Balaji
  • Article
    | Open Access

    Deep brain stimulation (DBS) is a symptomatic treatment of Parkinson’s disease (PD) that benefits only a minority of patients. Here, the authors show that activation of cortical somatostatin interneurons alleviates motor symptoms in a mouse model of PD and may constitute a less invasive alternative than DBS.

    • Sébastien Valverde
    • , Marie Vandecasteele
    • , Charlotte Piette
    • , Willy Derousseaux
    • , Giuseppe Gangarossa
    • , Asier Aristieta Arbelaiz
    • , Jonathan Touboul
    • , Bertrand Degos
    •  & Laurent Venance
  • Article
    | Open Access

    Increasingly large scRNA-seq datasets demand better and more scalable analysis tools. Here, the authors introduce a scalable unsupervised deep embedding algorithm that clusters scRNA-seq data by iteratively optimizing a clustering objective function and enables removal of batch effects.

    • Xiangjie Li
    • , Kui Wang
    • , Yafei Lyu
    • , Huize Pan
    • , Jingxiao Zhang
    • , Dwight Stambolian
    • , Katalin Susztak
    • , Muredach P. Reilly
    • , Gang Hu
    •  & Mingyao Li
  • Article
    | Open Access

    The cognitive computational mechanisms underlying the antidepressant treatment response of SSRIs is not well understood. Here the authors show that SSRI treatment in healthy subjects for a week manifests as an amplification of the perception of positive outcomes when learning occurs in a positive mood setting.

    • Jochen Michely
    • , Eran Eldar
    • , Ingrid M. Martin
    •  & Raymond J. Dolan
  • Article
    | Open Access

    Detailed understanding of how cancer cells transition from a drug sensitive to a tolerant state is lacking. Here, using single cell proteomic and metabolic data the authors uncover that isogenic BRAF mutant melanoma cells can take two distinct paths to become tolerant to BRAF inhibition.

    • Yapeng Su
    • , Melissa E. Ko
    • , Hanjun Cheng
    • , Ronghui Zhu
    • , Min Xue
    • , Jessica Wang
    • , Jihoon W. Lee
    • , Luke Frankiw
    • , Alexander Xu
    • , Stephanie Wong
    • , Lidia Robert
    • , Kaitlyn Takata
    • , Dan Yuan
    • , Yue Lu
    • , Sui Huang
    • , Antoni Ribas
    • , Raphael Levine
    • , Garry P. Nolan
    • , Wei Wei
    • , Sylvia K. Plevritis
    • , Guideng Li
    • , David Baltimore
    •  & James R. Heath
  • Article
    | Open Access

    In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

    • Xuemei Ji
    • , Semanti Mukherjee
    • , Maria Teresa Landi
    • , Yohan Bosse
    • , Philippe Joubert
    • , Dakai Zhu
    • , Ivan Gorlov
    • , Xiangjun Xiao
    • , Younghun Han
    • , Olga Gorlova
    • , Rayjean J. Hung
    • , Yonathan Brhane
    • , Robert Carreras-Torres
    • , David C. Christiani
    • , Neil Caporaso
    • , Mattias Johansson
    • , Geoffrey Liu
    • , Stig E. Bojesen
    • , Loic Le Marchand
    • , Demetrios Albanes
    • , Heike Bickeböller
    • , Melinda C. Aldrich
    • , William S. Bush
    • , Adonina Tardon
    • , Gad Rennert
    • , Chu Chen
    • , Jinyoung Byun
    • , Konstantin H. Dragnev
    • , John K. Field
    • , Lambertus FA. Kiemeney
    • , Philip Lazarus
    • , Shan Zienolddiny
    • , Stephen Lam
    • , Matthew B. Schabath
    • , Angeline S. Andrew
    • , Pier A. Bertazzi
    • , Angela C. Pesatori
    • , Nancy Diao
    • , Li Su
    • , Lei Song
    • , Ruyang Zhang
    • , Natasha Leighl
    • , Jakob S. Johansen
    • , Anders Mellemgaard
    • , Walid Saliba
    • , Christopher Haiman
    • , Lynne Wilkens
    • , Ana Fernandez-Somoano
    • , Guillermo Fernandez-Tardon
    • , Erik H. F. M. van der Heijden
    • , Jin Hee Kim
    • , Michael P. A. Davies
    • , Michael W. Marcus
    • , Hans Brunnström
    • , Jonas Manjer
    • , Olle Melander
    • , David C. Muller
    • , Kim Overvad
    • , Antonia Trichopoulou
    • , Rosario Tumino
    • , Gary E. Goodman
    • , Angela Cox
    • , Fiona Taylor
    • , Penella Woll
    • , Erich Wichmann
    • , Thomas Muley
    • , Angela Risch
    • , Albert Rosenberger
    • , Kjell Grankvist
    • , Mikael Johansson
    • , Frances Shepherd
    • , Ming-Sound Tsao
    • , Susanne M. Arnold
    • , Eric B. Haura
    • , Ciprian Bolca
    • , Ivana Holcatova
    • , Vladimir Janout
    • , Milica Kontic
    • , Jolanta Lissowska
    • , Anush Mukeria
    • , Simona Ognjanovic
    • , Tadeusz M. Orlowski
    • , Ghislaine Scelo
    • , Beata Swiatkowska
    • , David Zaridze
    • , Per Bakke
    • , Vidar Skaug
    • , Lesley M. Butler
    • , Kenneth Offit
    • , Preethi Srinivasan
    • , Chaitanya Bandlamudi
    • , Matthew D. Hellmann
    • , David B. Solit
    • , Mark E. Robson
    • , Charles M. Rudin
    • , Zsofia K. Stadler
    • , Barry S. Taylor
    • , Michael F. Berger
    • , Richard Houlston
    • , John McLaughlin
    • , Victoria Stevens
    • , David C. Nickle
    • , Ma’en Obeidat
    • , Wim Timens
    • , María Soler Artigas
    • , Sanjay Shete
    • , Hermann Brenner
    • , Stephen Chanock
    • , Paul Brennan
    • , James D. McKay
    •  & Christopher I. Amos
  • Article
    | Open Access

    Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.

    • Nayoung Kim
    • , Hong Kwan Kim
    • , Kyungjong Lee
    • , Yourae Hong
    • , Jong Ho Cho
    • , Jung Won Choi
    • , Jung-Il Lee
    • , Yeon-Lim Suh
    • , Bo Mi Ku
    • , Hye Hyeon Eum
    • , Soyean Choi
    • , Yoon-La Choi
    • , Je-Gun Joung
    • , Woong-Yang Park
    • , Hyun Ae Jung
    • , Jong-Mu Sun
    • , Se-Hoon Lee
    • , Jin Seok Ahn
    • , Keunchil Park
    • , Myung-Ju Ahn
    •  & Hae-Ock Lee
  • Article
    | Open Access

    Segregation of an MSH1 RNAi transgene produces non-genetic memory that displays transgenerational inheritance in Arabidopsis. Here, the authors compare memory and non-memory full-sib progenies to show the involvement of DNA methylation reprogramming, involving the RdDM pathway, in transition to a heritable memory state.

    • Xiaodong Yang
    • , Robersy Sanchez
    • , Hardik Kundariya
    • , Tom Maher
    • , Isaac Dopp
    • , Rosemary Schwegel
    • , Kamaldeep Virdi
    • , Michael J. Axtell
    •  & Sally A. Mackenzie
  • Article
    | Open Access

    Theta oscillations have been implicated in hippocampal processing but mechanisms constraining phase timing of specific cell types are unknown. Here, the authors combine single-cell and multisite recordings with evolutionary computational models to evaluate mechanisms of phase preference of deep and superficial CA1 pyramidal cells.

    • Andrea Navas-Olive
    • , Manuel Valero
    • , Teresa Jurado-Parras
    • , Adan de Salas-Quiroga
    • , Robert G. Averkin
    • , Giuditta Gambino
    • , Elena Cid
    •  & Liset M. de la Prida
  • Article
    | Open Access

    Immune infiltration provides critical information for health and disease, yet it is unclear what factors influence infiltration levels. Here, the authors analyze human tissue transcriptomes from the Genotype-Tissue Expression project to find infiltration patterns regulated by age, sex and host genetic information.

    • Andrew R. Marderstein
    • , Manik Uppal
    • , Akanksha Verma
    • , Bhavneet Bhinder
    • , Zakieh Tayyebi
    • , Jason Mezey
    • , Andrew G. Clark
    •  & Olivier Elemento
  • Article
    | Open Access

    The contribution of central and peripheral channels of nuclear pores to transport of transmembrane proteins is unclear. Here the authors show that most inner nuclear membrane proteins use only peripheral channels, but some extend nuclear localization signals into the central channel for directed nuclear transport.

    • Krishna C. Mudumbi
    • , Rafal Czapiewski
    • , Andrew Ruba
    • , Samuel L. Junod
    • , Yichen Li
    • , Wangxi Luo
    • , Christina Ngo
    • , Valentina Ospina
    • , Eric C. Schirmer
    •  & Weidong Yang
  • Article
    | Open Access

    Dpr (Defective proboscis extension response) and DIP (Dpr Interacting Proteins) are immunoglobulin-like cell-cell adhesion proteins that form highly specific pairwise interactions, which control synaptic connectivity during Drosophila development. Here, the authors combine a computational approach with binding affinity measurements and find that DIP/Dpr binding specificity is controlled by negative constraints that interfere with non-cognate binding.

    • Alina P. Sergeeva
    • , Phinikoula S. Katsamba
    • , Filip Cosmanescu
    • , Joshua J. Brewer
    • , Goran Ahlsen
    • , Seetha Mannepalli
    • , Lawrence Shapiro
    •  & Barry Honig
  • Article
    | Open Access

    It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition.

    • David P. Cook
    •  & Barbara C. Vanderhyden
  • Article
    | Open Access

    The role of long non-coding RNAs (lncRNAs) in metastatic colorectal cancer (mCRC) and treatment resistance is unclear. Here, the authors use transcriptome sequencing of matched normal, primary, and metastatic CRC tissues to discover and validate that lncRNA RAMS11 promotes metastasis and resistance to topoisomerase inhibitors in mCRC.

    • Jessica M. Silva-Fisher
    • , Ha X. Dang
    • , Nicole M. White
    • , Matthew S. Strand
    • , Bradley A. Krasnick
    • , Emily B. Rozycki
    • , Gejae G. L. Jeffers
    • , Julie G. Grossman
    • , Maureen K. Highkin
    • , Cynthia Tang
    • , Christopher R. Cabanski
    • , Abdallah Eteleeb
    • , Jacqueline Mudd
    • , S. Peter Goedegebuure
    • , Jingqin Luo
    • , Elaine R. Mardis
    • , Richard K. Wilson
    • , Timothy J. Ley
    • , Albert C. Lockhart
    • , Ryan C. Fields
    •  & Christopher A. Maher
  • Article
    | Open Access

    Recent research has shown that mutational signatures reflective of the history of a cancer can be detected in a cancer genome. Here, using whole genome sequencing of DNA repair deficient and proficient nematodes exposed to genotoxins, the authors show that these mutational signatures reflect both the initial DNA damage that was inflicted and the repair processes that ensue.

    • Nadezda V. Volkova
    • , Bettina Meier
    • , Víctor González-Huici
    • , Simone Bertolini
    • , Santiago Gonzalez
    • , Harald Vöhringer
    • , Federico Abascal
    • , Iñigo Martincorena
    • , Peter J. Campbell
    • , Anton Gartner
    •  & Moritz Gerstung
  • Article
    | Open Access

    A small set of promoters is used for most genetic construct design in S. cerevisiae. Here, the authors develop a predictive model of promoter activity trained on a data set of over one million sequences and use it to design large sets of high-activity promoters.

    • Benjamin J. Kotopka
    •  & Christina D. Smolke
  • Article
    | Open Access

    Taurine and indicine cattle have different desirable traits making them better adapted to different climates across the world. Here, Low et al. describe a pipeline to produce haplotype-resolved, chromosome-level genomes of Angus and Brahman cattle breeds from a crossbred individual and report on comparisons of the two genomes.

    • Wai Yee Low
    • , Rick Tearle
    • , Ruijie Liu
    • , Sergey Koren
    • , Arang Rhie
    • , Derek M. Bickhart
    • , Benjamin D. Rosen
    • , Zev N. Kronenberg
    • , Sarah B. Kingan
    • , Elizabeth Tseng
    • , Françoise Thibaud-Nissen
    • , Fergal J. Martin
    • , Konstantinos Billis
    • , Jay Ghurye
    • , Alex R. Hastie
    • , Joyce Lee
    • , Andy W. C. Pang
    • , Michael P. Heaton
    • , Adam M. Phillippy
    • , Stefan Hiendleder
    • , Timothy P. L. Smith
    •  & John L. Williams
  • Article
    | Open Access

    Dysregulation of mRNA alternative splicing is prevalent in cancers. Here, the authors characterized the landscape of aberrant alternative splicing during the development of prostate cancer, progression and therapeutic resistance and show that splicing modulator, E7107, reduces growth in castration-resistant prostate cancer.

    • Dingxiao Zhang
    • , Qiang Hu
    • , Xiaozhuo Liu
    • , Yibing Ji
    • , Hsueh-Ping Chao
    • , Yan Liu
    • , Amanda Tracz
    • , Jason Kirk
    • , Silvia Buonamici
    • , Ping Zhu
    • , Jianmin Wang
    • , Song Liu
    •  & Dean G. Tang
  • Article
    | Open Access

    Targeted mass spectrometry enables reproducible and accurate lipid quantification but dedicated software tools to develop targeted lipidomics assays are lacking. Here, the authors develop a targeted lipidomics workbench and lipid knowledgebase for the streamlined generation of targeted assays.

    • Bing Peng
    • , Dominik Kopczynski
    • , Brian S. Pratt
    • , Christer S. Ejsing
    • , Bo Burla
    • , Martin Hermansson
    • , Peter Imre Benke
    • , Sock Hwee Tan
    • , Mark Y. Chan
    • , Federico Torta
    • , Dominik Schwudke
    • , Sven W. Meckelmann
    • , Cristina Coman
    • , Oliver J. Schmitz
    • , Brendan MacLean
    • , Mailin-Christin Manke
    • , Oliver Borst
    • , Markus R. Wenk
    • , Nils Hoffmann
    •  & Robert Ahrends
  • Article
    | Open Access

    Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

    • Adam W. Whisnant
    • , Christopher S. Jürges
    • , Thomas Hennig
    • , Emanuel Wyler
    • , Bhupesh Prusty
    • , Andrzej J. Rutkowski
    • , Anne L’hernault
    • , Lara Djakovic
    • , Margarete Göbel
    • , Kristina Döring
    • , Jennifer Menegatti
    • , Robin Antrobus
    • , Nicholas J. Matheson
    • , Florian W. H. Künzig
    • , Guido Mastrobuoni
    • , Chris Bielow
    • , Stefan Kempa
    • , Chunguang Liang
    • , Thomas Dandekar
    • , Ralf Zimmer
    • , Markus Landthaler
    • , Friedrich Grässer
    • , Paul J. Lehner
    • , Caroline C. Friedel
    • , Florian Erhard
    •  & Lars Dölken
  • Article
    | Open Access

    Indels that are commonly found in cancer genomes are characterized by non-random sequence composition and localisation. Here, the authors described a method to investigate transcriptional strand asymmetries and sequence-context specific mechanisms that alter the likelihood of insertions and deletions.

    • Ilias Georgakopoulos-Soares
    • , Gene Koh
    • , Sophie E. Momen
    • , Josef Jiricny
    • , Martin Hemberg
    •  & Serena Nik-Zainal
  • Article
    | Open Access

    Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging men with limited therapeutic options. In this study, the authors describe the molecular characterization of BPH performing genomic, transcriptomic and epigenetic analysis of 18 BPH cases.

    • Deli Liu
    • , Jonathan E. Shoag
    • , Daniel Poliak
    • , Ramy S. Goueli
    • , Vaishali Ravikumar
    • , David Redmond
    • , Aram Vosoughi
    • , Jacqueline Fontugne
    • , Heng Pan
    • , Daniel Lee
    • , Domonique Thomas
    • , Keyan Salari
    • , Zongwei Wang
    • , Alessandro Romanel
    • , Alexis Te
    • , Richard Lee
    • , Bilal Chughtai
    • , Aria F. Olumi
    • , Juan Miguel Mosquera
    • , Francesca Demichelis
    • , Olivier Elemento
    • , Mark A. Rubin
    • , Andrea Sboner
    •  & Christopher E. Barbieri
  • Article
    | Open Access

    Traditional methods for determining cell type composition lack scalability, while single-cell technologies remain costly and noisy compared to bulk RNA-seq. Here, the authors present a highly efficient tool to measure cellular heterogeneity in bulk expression through robust integration of single-cell information.

    • Brandon Jew
    • , Marcus Alvarez
    • , Elior Rahmani
    • , Zong Miao
    • , Arthur Ko
    • , Kristina M. Garske
    • , Jae Hoon Sul
    • , Kirsi H. Pietiläinen
    • , Päivi Pajukanta
    •  & Eran Halperin
  • Article
    | Open Access

    Molecular analysis of archival formalin-fixed clinical tissues can be difficult. Here, researchers have developed MethCORR, an approach that infers gene expression from DNA methylation data and use the approach for molecular characterization and prognostication of colorectal cancer using archival samples.

    • Trine B. Mattesen
    • , Mads H. Rasmussen
    • , Juan Sandoval
    • , Halit Ongen
    • , Sigrid S. Árnadóttir
    • , Josephine Gladov
    • , Anna Martinez-Cardus
    • , Manuel Castro de Moura
    • , Anders H. Madsen
    • , Søren Laurberg
    • , Emmanouil T. Dermitzakis
    • , Manel Esteller
    • , Claus L. Andersen
    •  & Jesper B. Bramsen