Jun Prof Lars Barquist
Our research and approach
Recent years have seen accelerating development of high-throughput technologies in infection biology. Now, thousands of genetic loci can be simultaneously interrogated in a single experiment, providing an array of measurements of transcription, translation, regulatory interactions, and fitness effects. The bottleneck in advancing our understanding of pathogens now lies in moving from hypothesis-free screening through data integration to hypothesis generation. We develop new statistical, bioinformatic, and visualization approaches to overcome this bottleneck in the interpretation of complex post-genomic data.
Team members
Jun Prof Lars Barquist
Group Leader
Dr Laura Jenniches
Postdoc
Dr Regan Hayward
Postdoc
Bozena Mika-Gospodorz
PhD Student
Patrick Pfau
PhD Student
Shuba Varshini Alampalli
PhD Student
Yanying Yu
PhD Student
Titus Ebbecke
Master Student
Research projects
We analyse and integrate genomic and post-genomic data to provide insight into bacterial pathogenesis. We have been active in developing bioinformatics techniques to analyze and interpret the results of experiments using high-throughput sequencing, including transposon-insertion sequencing, CLIP-seq, and dual RNA-seq. We are actively developing new algorithms and statistical approaches to these kinds of data to provide insight into both host-microbe interactions and RNA-based regulation in bacterial pathogens.
We have also been active in applying machine learning tools to the evolution of bacterial pathogens using genome sequencing data. By dissecting the architecture of these machines, we have been able to extract new insights into how pathogens adapt to their hosts. We are currently investigating way to incorporate additional layers of information, such as gene expression information and mutations in non-coding RNA, into such models to provide a more comprehensive view of pathogen behavior.
Publications
2020
A high-resolution transcriptome map identifies small RNA regulation of metabolism in the gut microbe Bacteroides thetaiotaomicron
Ryan D, Jenniches L, Reichardt S, Barquist L, Westermann A (2020)
Nature Communications, 11 (1): 3557
Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
Mika-Gospodorz B, Giengkam S, Westermann A, Wongsantichon J, Kion-Crosby W, Chuenklin S, Wang L, Sunyakumthorn P, Sobota R, Subbian S, …, Barquist L, Salje J (2020)
Nature Communications, 11 (1): 3363
An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria
Elliott A, Huang J, Neve S, Zuegg J, Edwards I, Cain A, Boinett C, Barquist L, Lundberg C, Steen J, …, Strandh M, Cooper M (2020)
Nature Communications, 11 (1): 3184
The minimal meningococcal ProQ protein has an intrinsic capacity for structure-based global RNA recognition
Bauriedl S, Gerovac M, Heidrich N, Bischler T, Barquist L, Vogel J, Schoen C (2020)
Nature Communications, 11 (1): 2823
A decade of advances in transposon-insertion sequencing
Cain A, Barquist L, Goodman A, Paulsen I, Parkhill J, van Opijnen T (2020)
Nature Reviews Genetics, 21: 526-540
2019
Conditional Hfq Association with Small Noncoding RNAs in Pseudomonas aeruginosa Revealed through Comparative UV Cross-Linking Immunoprecipitation Followed by High-Throughput Sequencing
Chihara K, Bischler T, Barquist L, Monzon V, Noda N, Vogel J, Tsuneda S (2019)
mSystems, 4 (6)
Rapid transcriptional responses to serum exposure are associated with sensitivity and resistance to antibody-mediated complement killing in invasive Salmonella Typhimurium ST313
Ondari E, Klemm E, Msefula C, El Ghany M, Heath J, Pickard D, Barquist L, Dougan G, Kingsley R, MacLennan C (2019)
Wellcome Open Research, 4: 74
Transcriptional noise and exaptation as sources for bacterial sRNAs
Jose B, Gardner P, Barquist L (2019)
Biochemical Society Transactions, 47 (2): 527-539
2018
Global Maps of ProQ Binding In Vivo Reveal Target Recognition via RNA Structure and Stability Control at mRNA 3' Ends
Holmqvist E, Li L, Bischler T, Barquist L, Vogel J (2018)
Molecular Cell, 70 (5): 971-982
A global genomic approach uncovers novel components for twitching motility-mediated biofilm expansion in Pseudomonas aeruginosa
Nolan L, Whitchurch C, Barquist L, Katrib M, Boinett C, Mayho M, Goulding D, Charles I, Filloux A, Parkhill J, Cain A (2018)
Microbial Genomics, 4 (11): 00022
Functional analysis of Salmonella Typhi adaptation to survival in water
Kingsley R, Langridge G, Smith S, Makendi C, Fookes M, Wileman T, El Ghany M, Keith Turner A, Dyson Z, Sridhar S, …, Barquist L, Dougan G (2018)
Environmental Microbiology, 20 (11): 4079-4090
Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin
Cain A, Boinett C, Barquist L, Dordel J, Fookes M, Mayho M, Ellington M, Goulding D, Pickard D, Wick R, …, Parkhill J, Thomson N (2018)
Scientific Reports, 8 (1): 9868
Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella enterica
Wheeler N, Gardner P, Barquist L (2018)
PLoS Genetics, 14 (5): 10073
2017
RNA target profiles direct the discovery of virulence functions for the cold-shock proteins CspC and CspE
Michaux C, Holmqvist E, Vasicek E, Sharan M, Barquist L, Westermann A, Gunn J, Vogel J (2017)
Proceedings Of The National Academy Of Sciences Of The United States Of America, 114 (26): 6824-6829
Role of sapA and yfgA in Susceptibility to Antibody-Mediated Complement-Dependent Killing and Virulence of Salmonella enterica Serovar Typhimurium
Ondari E, Heath J, Klemm E, Langridge G, Barquist L, Goulding D, Clare S, Dougan G, Kingsley R, MacLennan C (2017)
Infection And Immunity, 85 (9): 00419-17
Resolving host-pathogen interactions by dual RNA-seq
Westermann A, Barquist L, Vogel J (2017)
PLoS Pathogens, 13 (2): 10060
2016
Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings
Feasey N, Hadfield J, Keddy K, Dallman T, Jacobs J, Deng X, Wigley P, Barquist L, Langridge G, Feltwell T, …, Gordon M, Thomson N (2016)
Nature Genetics, 48 (10): 1211-1217
Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo
Holmqvist E, Wright P, Li L, Bischler T, Barquist L, Reinhardt R, Backofen R, Vogel J (2016)
The EMBO Journal, 35 (9): 991-1011
The TraDIS toolkit: sequencing and analysis for dense transposon mutant libraries
Barquist L, Mayho M, Cummins C, Cain A, Boinett C, Page A, Langridge G, Quail M, Keane J, Parkhill J (2016)
Bioinformatics, 32 (7): 1109-11
Studying RNA Homology and Conservation with Infernal: From Single Sequences to RNA Families
Barquist L, Burge S, Gardner P (2016)
Current Protocols In Bioinformatics, 54: 1-12
Molecular phenotyping of infection-associated small non-coding RNAs
Barquist L, Westermann A, Vogel J (2016)
Philosophical Transactions Of The Royal Society Of London. Series B, Biological Sciences, 371 (1707): 20160
The in vitro and in vivo effects of constitutive light expression on a bioluminescent strain of the mouse enteropathogen Citrobacter rodentium
Read H, Mills G, Johnson S, Tsai P, Dalton J, Barquist L, Print C, Patrick W, Wiles S (2016)
PeerJ, 4: 2130
A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes
Wheeler N, Barquist L, Kingsley R, Gardner P (2016)
Bioinformatics, 32 (23): 3566-3574
2015
High-throughput analysis of gene essentiality and sporulation in Clostridium difficile
Dembek M, Barquist L, Boinett C, Cain A, Mayho M, Lawley T, Fairweather N, Fagan R (2015)
MBio, 6 (2): 02383
Patterns of genome evolution that have accompanied host adaptation in Salmonella
Langridge G, Fookes M, Connor T, Feltwell T, Feasey N, Parsons B, Seth-Smith H, Barquist L, Stedman A, Humphrey T, …, Dougan G, Thomson N (2015)
Proceedings Of The National Academy Of Sciences Of The United States Of America, 112 (3): 863-8
Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa
Okoro C, Barquist L, Connor T, Harris S, Clare S, Stevens M, Arends M, Hale C, Kane L, Pickard D, …, Dougan G, Kingsley R (2015)
PLoS Neglected Tropical Diseases, 9 (3): 00036
2014
Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism
Pettit L, Browne H, Yu L, Smits W, Fagan R, Barquist L, Martin M, Goulding D, Duncan S, Flint H, …, Choudhary J, Lawley T (2014)
BMC Genomics, 15: 160
Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling
Lindgreen S, Umu S, Lai A, Eldai H, Liu W, McGimpsey S, Wheeler N, Biggs P, Thomson N, Barquist L, Poole A, Gardner P (2014)
PLoS Computational Biology, 10 (10): 10039
Parallel independent evolution of pathogenicity within the genus Yersinia
Reuter S, Connor T, Barquist L, Walker D, Feltwell T, Harris S, Fookes M, Hall M, Petty N, Fuchs T, …, McNally A, Thomson N (2014)
Proceedings Of The National Academy Of Sciences Of The United States Of America, 111 (18): 6768-73
An introduction to RNA databases
Hoeppner M, Barquist L, Gardner P (2014)
In: RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods (eds Gorodkin J, Ruzzo W), Methods Mol Biol, 1097: 107-23
2013
Rfam 11.0: 10 years of RNA families
Burge S, Daub J, Eberhardt R, Tate J, Barquist L, Nawrocki E, Eddy S, Gardner P, Bateman A (2013)
Nucleic Acids Research, 41 (Database issue): 226-32
RNA-seq reveals the RNA binding proteins, Hfq and RsmA, play various roles in virulence, antibiotic production and genomic flux in Serratia sp. ATCC 39006
Wilf N, Reid A, Ramsay J, Williamson N, Croucher N, Gatto L, Hester S, Goulding D, Barquist L, Lilley K, …, Dougan G, Salmond G (2013)
BMC Genomics, 14: 822
A comparison of dense transposon insertion libraries in the Salmonella serovars Typhi and Typhimurium
Barquist L, Langridge G, Turner D, Phan M, Turner A, Bateman A, Parkhill J, Wain J, Gardner P (2013)
Nucleic Acids Research, 41 (8): 4549-64
Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection
Croucher N, Mitchell A, Gould K, Inverarity D, Barquist L, Feltwell T, Fookes M, Harris S, Dordel J, Salter S, …, Mitchell T, Bentley S (2013)
PLoS Genetics, 9 (10): 10038
The agr locus regulates virulence and colonization genes in Clostridium difficile 027
Martin M, Clare S, Goulding D, Faulds-Pain A, Barquist L, Browne H, Pettit L, Dougan G, Lawley T, Wren B (2013)
Journal Of Bacteriology, 195 (16): 3672-81
Approaches to querying bacterial genomes with transposon-insertion sequencing
Barquist L, Boinett C, Cain A (2013)
RNA Biology, 10 (7): 1161-9
Genome and transcriptome adaptation accompanying emergence of the definitive type 2 host-restricted Salmonella enterica serovar Typhimurium pathovar
Kingsley R, Kay S, Connor T, Barquist L, Sait L, Holt K, Sivaraman K, Wileman T, Goulding D, Clare S, …, Parkhill J, Dougan G (2013)
MBio, 4 (5): 00565-13
Characterization of the yehUT two-component regulatory system of Salmonella enterica Serovar Typhi and Typhimurium
Wong V, Pickard D, Barquist L, Sivaraman K, Page A, Hart P, Arends M, Holt K, Kane L, Mottram L, …, Kingsley R, Dougan G (2013)
PloS one, 8 (12): 84567
2012
A high-resolution view of genome-wide pneumococcal transformation
Croucher N, Harris S, Barquist L, Parkhill J, Bentley S (2012)
PLoS Pathogens, 8 (6): 10027
HandAlign: Bayesian multiple sequence alignment, phylogeny and ancestral reconstruction
Westesson O, Barquist L, Holmes I (2012)
Bioinformatics, 28 (8): 1170-1
2011
RNIE: genome-wide prediction of bacterial intrinsic terminators
Gardner P, Barquist L, Bateman A, Nawrocki E, Weinberg Z (2011)
Nucleic Acids Research, 39 (14): 5845-52
2009
Evolutionary modeling and prediction of non-coding RNAs in Drosophila
Bradley R, Uzilov A, Skinner M, Bendana Y, Barquist L, Holmes I (2009)
PloS one, 4 (8): 6478
2008
xREI: a phylo-grammar visualization webserver
Barquist L, Holmes I (2008)
Nucleic Acids Research, 36 (Web Server issue): 65-