Systems biology

  • Article | | open

    Pseudomonas aeruginosa releases redox-active metabolites called phenazines. Here, the authors use metabolic imaging by stimulated Raman scattering microscopy to show that phenazines antagonize the effects of antibiotics on P. aeruginosa biofilms by modulating bacterial metabolism.

    • Konstanze T. Schiessl
    • , Fanghao Hu
    • , Jeanyoung Jo
    • , Sakila Z. Nazia
    • , Bryan Wang
    • , Alexa Price-Whelan
    • , Wei Min
    •  & Lars E. P. Dietrich
  • Article | | open

    The diurnal cycle exerts influences on various aspects of plant biology. Here, the authors generate and compare diurnal transcriptomics data from nine members of Archaeplastida representing major clades.

    • Camilla Ferrari
    • , Sebastian Proost
    • , Marcin Janowski
    • , Jörg Becker
    • , Zoran Nikoloski
    • , Debashish Bhattacharya
    • , Dana Price
    • , Takayuki Tohge
    • , Arren Bar-Even
    • , Alisdair Fernie
    • , Mark Stitt
    •  & Marek Mutwil
  • Article | | open

    High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.

    • Moriah Gidoni
    • , Omri Snir
    • , Ayelet Peres
    • , Pazit Polak
    • , Ida Lindeman
    • , Ivana Mikocziova
    • , Vikas Kumar Sarna
    • , Knut E. A. Lundin
    • , Christopher Clouser
    • , Francois Vigneault
    • , Andrew M. Collins
    • , Ludvig M. Sollid
    •  & Gur Yaari
  • Article | | open

    Many Gram-negative bacteria rely on a type III secretion system (T3SS) for their pathogenicity. Here authors present the cryo-EM structure of the E.coli T3SS ATPase-central stalk complex, which forms a homohexameric, asymmetric pore with different functional states.

    • Dorothy D. Majewski
    • , Liam J. Worrall
    • , Chuan Hong
    • , Claire E. Atkinson
    • , Marija Vuckovic
    • , Nobuhiko Watanabe
    • , Zhiheng Yu
    •  & Natalie C. J. Strynadka
  • Article | | open

    The pathogen Pseudomonas aeruginosa undergoes complex trait adaptation within cystic fibrosis patients. Here, Bartell, Sommer, and colleagues use statistical modeling of longitudinal isolates to characterize the joint genetic and phenotypic evolutionary trajectories of P. aeruginosa within hosts.

    • Jennifer A. Bartell
    • , Lea M. Sommer
    • , Janus A. J. Haagensen
    • , Anne Loch
    • , Rocio Espinosa
    • , Søren Molin
    •  & Helle Krogh Johansen
  • Article | | open

    Development of bacterial resistance to an antibiotic can lead to collateral sensitivity to another drug. Here, the authors study collateral sensitivity conferred by mutations in the horizontally acquired β-lactamase CTX-M-15, and identify antibiotic combinations that constrain the evolution of resistance.

    • Carola E. H. Rosenkilde
    • , Christian Munck
    • , Andreas Porse
    • , Marius Linkevicius
    • , Dan I. Andersson
    •  & Morten O. A. Sommer
  • Article | | open

    End-product toxicity, culture contamination, and energy efficient product recovery are long-standing issues in bioprocessing. Here, the authors address these problems using a fermentation strategy that combines microbial production of branched alcohols with supercritical carbon dioxide extraction.

    • Jason T. Boock
    • , Adam J. E. Freedman
    • , Geoffrey A. Tompsett
    • , Sarah K. Muse
    • , Audrey J. Allen
    • , Luke A. Jackson
    • , Bernardo Castro-Dominguez
    • , Michael T. Timko
    • , Kristala L. J. Prather
    •  & Janelle R. Thompson
  • Article | | open

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    • , Zhaoyu Zhang
    • , Xi Chen
    • , Xiangzhi Zeng
    • , Yiyang Zhang
    • , Tingyue Deng
    • , Mengfei Ren
    • , Zheng Sun
    • , Rui Jiang
    •  & Zhen Xie
  • Article | | open

    Producing individual cannabinoids by metabolically engineered microbes has proven challenging. Here, the authors develop a cell-free enzymatic prenylating system to generate isoprenyl pyrophosphate substrates directly from glucose and produce both common and rare cannabinoids at >1 g/L.

    • Meaghan A. Valliere
    • , Tyler P. Korman
    • , Nicholas B. Woodall
    • , Gregory A. Khitrov
    • , Robert E. Taylor
    • , David Baker
    •  & James U. Bowie
  • Article | | open

    An unresolved problem in neuroscience is to determine the relevant timescale for understanding spatiotemporal dynamics of the brain. Here, the authors introduce a new framework to study the different timescales through binning the output of a generative model of neural activity.

    • Gustavo Deco
    • , Josephine Cruzat
    •  & Morten L. Kringelbach
  • Article | | open

    Host microbiomes are feasible sources for drug discovery. Here, using large-scale isolations, bioactivity assays and omics, the authors uncover the antimicrobial potential of insect-associated Streptomyces and identify a compound, cyphomycin, active against multidrug-resistant fungal pathogens.

    • Marc G. Chevrette
    • , Caitlin M. Carlson
    • , Humberto E. Ortega
    • , Chris Thomas
    • , Gene E. Ananiev
    • , Kenneth J. Barns
    • , Adam J. Book
    • , Julian Cagnazzo
    • , Camila Carlos
    • , Will Flanigan
    • , Kirk J. Grubbs
    • , Heidi A. Horn
    • , F. Michael Hoffmann
    • , Jonathan L. Klassen
    • , Jennifer J. Knack
    • , Gina R. Lewin
    • , Bradon R. McDonald
    • , Laura Muller
    • , Weilan G. P. Melo
    • , Adrián A. Pinto-Tomás
    • , Amber Schmitz
    • , Evelyn Wendt-Pienkowski
    • , Scott Wildman
    • , Miao Zhao
    • , Fan Zhang
    • , Tim S. Bugni
    • , David R. Andes
    • , Monica T. Pupo
    •  & Cameron R. Currie
  • Article | | open

    Combination therapy for Buruli ulcer (BU) is suboptimal. Here, Liu et al. show that the candidate drug TB47 has potent bactericidal activity against Mycobacterium ulcerans in vitro and in a mouse model, which underscores its potential for shortening the course of BU and treating other mycobacterial diseases.

    • Yang Liu
    • , Yamin Gao
    • , Jianxiong Liu
    • , Yaoju Tan
    • , Zhiyong Liu
    • , Chiranjibi Chhotaray
    • , Huofeng Jiang
    • , Zhili Lu
    • , Gift Chiwala
    • , Shuai Wang
    • , Gaelle Makafe
    • , Md Mahmudul Islam
    • , H. M. Adnan Hameed
    • , Xingshan Cai
    • , Changwei Wang
    • , Xinjie Li
    • , Shouyong Tan
    •  & Tianyu Zhang
  • Article | | open

    Genetic logic devices allow the host cell to incorporate multiple inputs to determine output behaviour. Here the authors provide a framework for engineering reliable recombinase-based devices and demonstrate 4-input logic in a multicellular system.

    • Sarah Guiziou
    • , Pauline Mayonove
    •  & Jerome Bonnet
  • Article | | open

    Focal amplifications are prevalent in many cancer genomes. Here, the authors present AmpliconArchitect (AA), a computational tool for reconstructing their architecture, and reveal an extrachromosomal origin for focal amplifications, including hybrid human-virus elements in HPV-mediated cancers.

    • Viraj Deshpande
    • , Jens Luebeck
    • , Nam-Phuong D. Nguyen
    • , Mehrdad Bakhtiari
    • , Kristen M. Turner
    • , Richard Schwab
    • , Hannah Carter
    • , Paul S. Mischel
    •  & Vineet Bafna
  • Article | | open

    The Cas12b family of CRISPR nucleases has been underutilized in mammalian cells due to the high temperature requirement of known members. Here the authors engineer BhCas12b to overcome this limitation for robust and specific genome editing applications in human cells.

    • Jonathan Strecker
    • , Sara Jones
    • , Balwina Koopal
    • , Jonathan Schmid-Burgk
    • , Bernd Zetsche
    • , Linyi Gao
    • , Kira S. Makarova
    • , Eugene V. Koonin
    •  & Feng Zhang
  • Article | | open

    The evolution of resistance to an antibiotic can render bacteria more susceptible, or more resistant, to a second antibiotic. Here, Nichol et al. provide evidence that the final outcome can be fairly stochastic and depends on the shape of the evolutionary fitness landscape.

    • Daniel Nichol
    • , Joseph Rutter
    • , Christopher Bryant
    • , Andrea M. Hujer
    • , Sai Lek
    • , Mark D. Adams
    • , Peter Jeavons
    • , Alexander R. A. Anderson
    • , Robert A. Bonomo
    •  & Jacob G. Scott
  • Article | | open

    Near-infrared (NIR) fluorescent proteins (FPs) offer advantages for spectral multiplexing and deep-tissue imaging. Here the authors engineer a smaller NIR FP based on the unexplored cyanobacteriochrome photoreceptor and demonstrate its use in various applications in cell culture as well as whole-body imaging in vivo in mice.

    • Olena S. Oliinyk
    • , Anton A. Shemetov
    • , Sergei Pletnev
    • , Daria M. Shcherbakova
    •  & Vladislav V. Verkhusha
  • Article | | open

    Tissue-resident macrophages are highly specialized phagocytes that serve multiple functions. Here, using high-dimension analyses and fate-mapping experiments, the authors show that fetal liver-derived macrophages dominate the mammary gland in neonatal and adult, and display characteristic phenotypes and functions.

    • Norma Jäppinen
    • , Inês Félix
    • , Emmi Lokka
    • , Sofia Tyystjärvi
    • , Anne Pynttäri
    • , Tiina Lahtela
    • , Heidi Gerke
    • , Kati Elima
    • , Pia Rantakari
    •  & Marko Salmi
  • Article | | open

    Biological complexity has impeded our ability to predict the dynamics of mutualistic interactions. Here, the authors deduce a general rule to predict outcomes of mutualistic systems and introduce an approach that permits making predictions even in the absence of knowledge of mechanistic details.

    • Feilun Wu
    • , Allison J. Lopatkin
    • , Daniel A. Needs
    • , Charlotte T. Lee
    • , Sayan Mukherjee
    •  & Lingchong You
  • Article | | open

    To explain the neural correlates of behavior and its variability, one must analyze single-trial population dynamics. Here, the authors develop a statistical method that extracts low-dimensional dynamics that explain behavior better than high-dimensional neural activity revealing unexpected structure.

    • Ziqiang Wei
    • , Hidehiko Inagaki
    • , Nuo Li
    • , Karel Svoboda
    •  & Shaul Druckmann
  • Article | | open

    Salmonella Typhimurium replicates within host phagocytes. Here, the authors show that a known psychoactive drug (metergoline) inhibits growth of the pathogen in macrophages, disrupts the proton motive force at the bacterial cytoplasmic membrane, and extends animal survival during systemic infection.

    • Michael J. Ellis
    • , Caressa N. Tsai
    • , Jarrod W. Johnson
    • , Shawn French
    • , Wael Elhenawy
    • , Steffen Porwollik
    • , Helene Andrews-Polymenis
    • , Michael McClelland
    • , Jakob Magolan
    • , Brian K. Coombes
    •  & Eric D. Brown
  • Article | | open

    Anti-CRISPR proteins derived from phage can abrogate CRISPR activity. The authors repurpose these molecules for demonstrating genomic write-protection and pre-programmed gene expression circuits.

    • Muneaki Nakamura
    • , Prashanth Srinivasan
    • , Michael Chavez
    • , Matthew A. Carter
    • , Antonia A. Dominguez
    • , Marie La Russa
    • , Matthew B. Lau
    • , Timothy R. Abbott
    • , Xiaoshu Xu
    • , Dehua Zhao
    • , Yuchen Gao
    • , Nathan H. Kipniss
    • , Christina D. Smolke
    • , Joseph Bondy-Denomy
    •  & Lei S. Qi
  • Article | | open

    Increased abundance of antibiotic resistance genes in the environment may be due to selection pressure by residual antibiotics, or to contamination with resistant bacteria from human faeces. Here, Karkman et al. analyze metagenomic data and find evidence supporting the second scenario in most cases.

    • Antti Karkman
    • , Katariina Pärnänen
    •  & D. G. Joakim Larsson
  • Article | | open

    The same protein abundance can be achieved by many combinations of transcription, translation and degradation rates. Here, the authors find that genes combining high transcription with low translation rate are rare due to a trade-off between the cost of transcription and expression noise.

    • Jean Hausser
    • , Avi Mayo
    • , Leeat Keren
    •  & Uri Alon
  • Article | | open

    The respiratory system is transformed in terms of functional change at birth to adapt to breathing air. Here, the authors examine the molecular changes behind the first breath in the mouse by Drop-seq based RNA sequencing, identifying activation of the unfolded protein response as a perinatal adaptation of the lung.

    • Minzhe Guo
    • , Yina Du
    • , Jason J. Gokey
    • , Samriddha Ray
    • , Sheila M. Bell
    • , Mike Adam
    • , Parvathi Sudha
    • , Anne Karina Perl
    • , Hitesh Deshmukh
    • , S. Steven Potter
    • , Jeffrey A. Whitsett
    •  & Yan Xu
  • Article | | open

    Serine synthesis from glucose is required even when serine is available from the environment. Here, the authors explain this paradox by showing that the enzyme PHGDH enables nucleotide synthesis by coordinating anabolic fluxes related to central carbon metabolism, independent of its role in serine production.

    • Michael A. Reid
    • , Annamarie E. Allen
    • , Shiyu Liu
    • , Maria V. Liberti
    • , Pei Liu
    • , Xiaojing Liu
    • , Ziwei Dai
    • , Xia Gao
    • , Qian Wang
    • , Ying Liu
    • , Luhua Lai
    •  & Jason W. Locasale
  • Article | | open

    Molecular circuits implementing fold-change detection (FCD) allow cells to respond to fold-change in signals regardless of absolute levels. Here, the authors find that meaning, attention and saturation similarly form an FCD circuit and produce the observed dynamics of human behavior in creative search.

    • Yuval Hart
    • , Hagar Goldberg
    • , Ella Striem-Amit
    • , Avraham E. Mayo
    • , Lior Noy
    •  & Uri Alon
  • Article | | open

    Genome-wide libraries for CRISPR knockout, interference, and activation have allowed the systemic interrogation of gene function. Here, the authors evaluate the Brunello CRISPRko library and introduce Dolcetto and Calabrese for CRISPRi and CRISPRa, respectively.

    • Kendall R. Sanson
    • , Ruth E. Hanna
    • , Mudra Hegde
    • , Katherine F. Donovan
    • , Christine Strand
    • , Meagan E. Sullender
    • , Emma W. Vaimberg
    • , Amy Goodale
    • , David E. Root
    • , Federica Piccioni
    •  & John G. Doench
  • Article | | open

    The bacterial complex QrcABCD plays a key role in the bioenergetics of sulfate respiration. Here, Duarte et al. show that this complex is electrogenic, with protons and electrons required for quinone reduction being extracted from opposite sides of the membrane.

    • Américo G. Duarte
    • , Teresa Catarino
    • , Gaye F. White
    • , Diana Lousa
    • , Sinje Neukirchen
    • , Cláudio M. Soares
    • , Filipa L. Sousa
    • , Thomas A. Clarke
    •  & Inês A. C. Pereira
  • Article | | open

    Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). Existing anti-tubercular drugs have been used to treat the condition with varying success. Here, the authors show that a clinical-stage drug candidate for tuberculosis, Q203, is effective at killing M. ulcerans and is a promising therapeutic candidate for BU.

    • Nicole Scherr
    • , Raphael Bieri
    • , Sangeeta S. Thomas
    • , Aurélie Chauffour
    • , Nitin Pal Kalia
    • , Paul Schneide
    • , Marie-Thérèse Ruf
    • , Araceli Lamelas
    • , Malathy S. S. Manimekalai
    • , Gerhard Grüber
    • , Norihisa Ishii
    • , Koichi Suzuki
    • , Marcel Tanner
    • , Garrett C. Moraski
    • , Marvin J. Miller
    • , Matthias Witschel
    • , Vincent Jarlier
    • , Gerd Pluschke
    •  & Kevin Pethe
  • Article | | open

    Noisy gene expression leading to phenotypic variability can help organisms to survive in changing environments. Here, Patange et al. show that noisy expression of a stress response regulator, RpoS, allows E. coli cells to modulate their growth rates to survive future adverse environments.

    • Om Patange
    • , Christian Schwall
    • , Matt Jones
    • , Casandra Villava
    • , Douglas A. Griffith
    • , Andrew Phillips
    •  & James C. W. Locke
  • Article | | open

    Interventions in metabolic networks can improve microbes for chemical production. Here, the authors develop a tool to identify metabolic valves that can decouple growth and production to systematically improve the rate and yield of biochemical production processes.

    • Naveen Venayak
    • , Axel von Kamp
    • , Steffen Klamt
    •  & Radhakrishnan Mahadevan
  • Article | | open

    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
  • Article | | open

    Migration can increase survival of a metapopulation by enabling recolonization after local extinction. Here, Gokhale et al. use both microbial experiments and mechanistic modeling to show that moderate levels of migration can increase survival by altering oscillatory population dynamics.

    • Shreyas Gokhale
    • , Arolyn Conwill
    • , Tanvi Ranjan
    •  & Jeff Gore
  • Article | | open

    Bacterial infections and antibiotic resistance are an increasing concern for the world. Here the authors report a class of cationic antimicrobial polymers that cluster local facial amphiphilicity from repeating units to enhance interactions with bacterial membranes without requiring a high unfavorable entropic loss.

    • Md Anisur Rahman
    • , Marpe Bam
    • , Edgar Luat
    • , Moumita Sharmin Jui
    • , Mitra S. Ganewatta
    • , Tinom Shokfai
    • , Mitzi Nagarkatti
    • , Alan W. Decho
    •  & Chuanbing Tang
  • Article | | open

    Brain–machine interfaces typically decode arm velocity from motor cortical neurons to move neuroprostheses, but performance of these devices is degraded by erroneous extraction of speed from the neuronal firing patterns. Here, the authors show that this error can be corrected by using a hybrid artificial neural network approach.

    • Yoh Inoue
    • , Hongwei Mao
    • , Steven B. Suway
    • , Josue Orellana
    •  & Andrew B. Schwartz
  • Article | | open

    Experimental data on enzyme turnover numbers is sparse and noisy. Here, the authors use machine learning to successfully predict enzyme turnover numbers for E. coli, and show that using these to parameterize mechanistic genome-scale models enhances their predictive accuracy.

    • David Heckmann
    • , Colton J. Lloyd
    • , Nathan Mih
    • , Yuanchi Ha
    • , Daniel C. Zielinski
    • , Zachary B. Haiman
    • , Abdelmoneim Amer Desouki
    • , Martin J. Lercher
    •  & Bernhard O. Palsson
  • Article | | open

    The software Optimer has aided the programmable one-pot oligosaccharide synthesis with a library of 50 Building BLocks (BBLs). Here, the authors expanded Optimer's validated and virtual libraries of BBLs and developed Auto-CHO, a software which allows the one-pot programmable synthesis of more complex glycans.

    • Cheng-Wei Cheng
    • , Yixuan Zhou
    • , Wen-Harn Pan
    • , Supriya Dey
    • , Chung-Yi Wu
    • , Wen-Lian Hsu
    •  & Chi-Huey Wong
  • Article | | open

    Autoantibodies are implicated in autoimmunity, but may also be present in healthy individuals. Here the authors find that the autoantibody specificity signatures against various G protein-coupled receptors are associated with multiple parameters, including disease states, to imply a physiological function in maintaining immune homeostasis.

    • Otavio Cabral-Marques
    • , Alexandre Marques
    • , Lasse Melvær Giil
    • , Roberta De Vito
    • , Judith Rademacher
    • , Jeannine Günther
    • , Tanja Lange
    • , Jens Y. Humrich
    • , Sebastian Klapa
    • , Susanne Schinke
    • , Lena F. Schimke
    • , Gabriele Marschner
    • , Silke Pitann
    • , Sabine Adler
    • , Ralf Dechend
    • , Dominik N. Müller
    • , Ioana Braicu
    • , Jalid Sehouli
    • , Kai Schulze-Forster
    • , Tobias Trippel
    • , Carmen Scheibenbogen
    • , Annetine Staff
    • , Peter R. Mertens
    • , Madlen Löbel
    • , Justin Mastroianni
    • , Corinna Plattfaut
    • , Frank Gieseler
    • , Duska Dragun
    • , Barbara Elizabeth Engelhardt
    • , Maria J. Fernandez-Cabezudo
    • , Hans D. Ochs
    • , Basel K. al-Ramadi
    • , Peter Lamprecht
    • , Antje Mueller
    • , Harald Heidecke
    •  & Gabriela Riemekasten
  • Article | | open

    Zelda is a pioneer factor that regulates transcription in Drosophila embryos. Here, the authors use quantitative live imaging and mathematical modeling to measure the effect of Zelda on transcriptional dynamics and memory, observing temporal control of gene expression by Zelda through transient interactions in hubs.

    • Jeremy Dufourt
    • , Antonio Trullo
    • , Jennifer Hunter
    • , Carola Fernandez
    • , Jorge Lazaro
    • , Matthieu Dejean
    • , Lucas Morales
    • , Saida Nait-Amer
    • , Katharine N. Schulz
    • , Melissa M. Harrison
    • , Cyril Favard
    • , Ovidiu Radulescu
    •  & Mounia Lagha
  • Article | | open

    Identifying cell intrinsic mechanisms promoting metastasis are necessary to develop new cancer therapeutics. Here they do cross-species computational analysis and identify nuclear receptor binding SET domain Protein 2 (NSD2) as a driver of prostate cancer metastasis.

    • Alvaro Aytes
    • , Arianna Giacobbe
    • , Antonina Mitrofanova
    • , Katia Ruggero
    • , Joanna Cyrta
    • , Juan Arriaga
    • , Luis Palomero
    • , Sonia Farran-Matas
    • , Mark A. Rubin
    • , Michael M. Shen
    • , Andrea Califano
    •  & Cory Abate-Shen
  • Article | | open

    Mechanisms underlying increasing artemisinin resistance of Plasmodium in Southeast Asia remain unclear. Here, Zhu et al. integrate TWAS, GWAS and eQTL analyses for 773 P. falciparum isolates and identify genetic and transcriptomic backgrounds to artemisinin resistance.

    • Lei Zhu
    • , Jaishree Tripathi
    • , Frances Maureen Rocamora
    • , Olivo Miotto
    • , Rob van der Pluijm
    • , Till S. Voss
    • , Sachel Mok
    • , Dominic P. Kwiatkowski
    • , François Nosten
    • , Nicholas P. J. Day
    • , Nicholas J. White
    • , Arjen M. Dondorp
    • , Zbynek Bozdech
    • , Aung Pyae Phyo
    • , Elizabeth A. Ashley
    • , Frank Smithuis
    • , Khin Lin
    • , Kyaw Myo Tun
    • , M Abul Faiz
    • , Mayfong Mayxay
    • , Mehul Dhorda
    • , Nguyen Thanh Thuy-Nhien
    • , Paul N. Newton
    • , Sasithon Pukrittayakamee
    • , Tin M. Hlaing
    • , Tran Tinh Hien
    •  & Ye Htut
  • Article | | open

    Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.

    • Christopher K. E. Bleck
    • , Yuho Kim
    • , T. Bradley Willingham
    •  & Brian Glancy