Jun Prof Lars Barquist
Integrative Informatics for Infection Biology
We develop systems approaches to RNA and infection, using modern visualization, data science, and machine learning technologies to integrate large-scale functional genomics data.
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 Eva Weiß
Postdoc

Dr Laura Jenniches
Postdoc

Dr Regan Hayward
Postdoc

Dr Willow Kion-Crosby
Postdoc

Bozena Mika-Gospodorz
PhD Student

Mingjing Kang
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 AJ (2020)
Nature Communications 11: 3557
Dual RNA-seq of Orientia tsutsugamushi informs on host-pathogen interactions for this neglected intracellular human pathogen
Mika-Gospodorz B, Giengkam S, Westermann AJ, Wongsantichon J, Kion-Crosby W, Chuenklin S, Wang LC, Sunyakumthorn P, Sobota RM, Subbian S, …, Barquist L, Salje J (2020)
Nature Communications 11: 3363
An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria
Elliott AG, Huang JX, Neve S, Zuegg J, Edwards IA, Cain AK, Boinett CJ, Barquist L, Lundberg CV, Steen J, …, Strandh M, Cooper MA (2020)
Nature Communications 11: 3184
A decade of advances in transposon-insertion sequencing
Cain AK, Barquist L, Goodman AL, Paulsen IT, Parkhill J, van Opijnen T (2020)
Nature Reviews Genetics 21 (9): 526-540
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: 2823
Global identification of RsmA/N binding sites in Pseudomonas aeruginosa by in vivo UV CLIP-seq
Chihara K, Barquist L, Takasugi K, Noda N, Tsuneda S (2020)
Preprint
An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important Gram-positive bacterium
Fuchs M, Lamm-Schmidt V, Ponath F, Jenniches L, Barquist L, Vogel J, Faber F (2020)
Preprint
A global data-driven census of Salmonella small proteins and their potential functions in bacterial virulence
Venturini E, Svensson SL, Maaß S, Gelhausen R, Eggenhofer F, Li L, Cain AK, Parkhill J, Becher D, Backofen R, …, Westermann AJ, Vogel J (2020)
microLife 1 (1): 597
Single-Nucleotide RNA Maps for the Two Major Nosocomial Pathogens Enterococcus faecalis and Enterococcus faecium
Michaux C, Hansen EE, Jenniches L, Gerovac M, Barquist L, Vogel J (2020)
Frontiers in Cellular and Infection Microbiology 10: 60032
Whole genome sequencing of Thametopoea pityocampa revealed putative pesticide targets
Shahraki A, Yu Y, Gul ZM, Liang C, Iyison NB (2020)
Genomics 112 (6): 4203-4207
Global discovery of bacterial RNA-binding proteins by RNase-sensitive gradient profiles reports a new FinO domain protein
Gerovac M, El Mouali Y, Kuper J, Kisker C, Barquist L, Vogel J (2020)
RNA 26 (10): 1448-1463
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 VA, Noda N, Vogel J, Tsuneda S (2019)
mSystems 4 (6): 00590-19
Rapid transcriptional responses to serum exposure are associated with sensitivity and resistance to antibody-mediated complement killing in invasive Salmonella Typhimurium ST313
Ondari EM, Klemm EJ, Msefula CL, El Ghany MA, Heath JN, Pickard DJ, Barquist L, Dougan G, Kingsley RA, MacLennan CA (2019)
Wellcome Open Research 4: 74
Transcriptional noise and exaptation as sources for bacterial sRNAs
Jose BR, Gardner PP, 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
Functional analysis of Salmonella Typhi adaptation to survival in water
Kingsley RA, Langridge G, Smith SE, Makendi C, Fookes M, Wileman TM, El Ghany MA, Keith Turner A, Dyson ZA, Sridhar S, …, Barquist L, Dougan G (2018)
Environmental Microbiology 20 (11): 4079-4090
A global genomic approach uncovers novel components for twitching motility-mediated biofilm expansion in Pseudomonas aeruginosa
Nolan LM, Whitchurch CB, Barquist L, Katrib M, Boinett CJ, Mayho M, Goulding D, Charles IG, Filloux A, Parkhill J, Cain AK (2018)
Microbial Genomics 4 (11): 00022
Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella enterica
Wheeler NE, Gardner PP, Barquist L (2018)
PLOS Genetics 14 (5): 10073
Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin
Cain AK, Boinett CJ, Barquist L, Dordel J, Fookes M, Mayho M, Ellington MJ, Goulding D, Pickard D, Wick RR, …, Parkhill J, Thomson NR (2018)
Scientific Reports 8 (1): 9868
2017
The primary transcriptome of Neisseria meningitidis and its interaction with the RNA chaperone Hfq
Heidrich N, Bauriedl S, Barquist L, Li L, Schoen C, Vogel J (2017)
Nucleic Acids Research 45 (10): 6147-6167
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 AJ, Gunn JS, 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 EM, Heath JN, Klemm EJ, Langridge G, Barquist L, Goulding DA, Clare S, Dougan G, Kingsley RA, MacLennan CA (2017)
Infection and Immunity 85 (9): 00419-17
Resolving host-pathogen interactions by dual RNA-seq
Westermann AJ, 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 NA, Hadfield J, Keddy KH, Dallman TJ, Jacobs J, Deng X, Wigley P, Barquist L, Langridge GC, Feltwell T, …, Gordon MA, Thomson NR (2016)
Nature Genetics 48 (10): 1211-1217
Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions
Westermann AJ, Forstner KU, Amman F, Barquist L, Chao Y, Schulte LN, Muller L, Reinhardt R, Stadler PF, Vogel J (2016)
Nature 529 (7587): 496-501
Global RNA recognition patterns of post-transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo
Holmqvist E, Wright PR, 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 AK, Boinett CJ, Page AJ, Langridge GC, Quail MA, Keane JA, Parkhill J (2016)
Bioinformatics 32 (7): 1109-11
Studying RNA Homology and Conservation with Infernal: From Single Sequences to RNA Families
Barquist L, Burge SW, Gardner PP (2016)
Current Protocols in Bioinformatics 54: 1-12
Molecular phenotyping of infection-associated small non-coding RNAs
Barquist L, Westermann AJ, Vogel J (2016)
Philosophical Transactions of the Royal Society of London 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 HM, Mills G, Johnson S, Tsai P, Dalton J, Barquist L, Print CG, Patrick WM, Wiles S (2016)
PeerJ 4: 2130
A profile-based method for identifying functional divergence of orthologous genes in bacterial genomes
Wheeler NE, Barquist L, Kingsley RA, Gardner PP (2016)
Bioinformatics 32 (23): 3566-3574
2015
Accelerating Discovery and Functional Analysis of Small RNAs with New Technologies
Barquist L, Vogel J (2015)
Annual Review of Genetics 49: 367-94
High-throughput analysis of gene essentiality and sporulation in Clostridium difficile
Dembek M, Barquist L, Boinett CJ, Cain AK, Mayho M, Lawley TD, Fairweather NF, Fagan RP (2015)
mBio 6 (2): 02383
Patterns of genome evolution that have accompanied host adaptation in Salmonella
Langridge GC, Fookes M, Connor TR, Feltwell T, Feasey N, Parsons BN, Seth-Smith HM, Barquist L, Stedman A, Humphrey T, …, Dougan G, Thomson NR (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 CK, Barquist L, Connor TR, Harris SR, Clare S, Stevens MP, Arends MJ, Hale C, Kane L, Pickard DJ, …, Dougan G, Kingsley RA (2015)
PLOS Neglected Tropical Diseases 9 (3): 00036
2014
Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism
Pettit LJ, Browne HP, Yu L, Smits WK, Fagan RP, Barquist L, Martin MJ, Goulding D, Duncan SH, Flint HJ, …, Choudhary JS, Lawley TD (2014)
BMC Genomics 15: 160
Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling
Lindgreen S, Umu SU, Lai AS, Eldai H, Liu W, McGimpsey S, Wheeler NE, Biggs PJ, Thomson NR, Barquist L, Poole AM, Gardner PP (2014)
PLOS Computational Biology 10 (10): 10039
Parallel independent evolution of pathogenicity within the genus Yersinia
Reuter S, Connor TR, Barquist L, Walker D, Feltwell T, Harris SR, Fookes M, Hall ME, Petty NK, Fuchs TM, …, McNally A, Thomson NR (2014)
Proceedings of the National Academy of Sciences of the United States of America 111 (18): 6768-73
An introduction to RNA databases
Hoeppner MP, Barquist L, Gardner PP (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 SW, Daub J, Eberhardt R, Tate J, Barquist L, Nawrocki EP, Eddy SR, Gardner PP, 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 NM, Reid AJ, Ramsay JP, Williamson NR, Croucher NJ, Gatto L, Hester SS, Goulding D, Barquist L, Lilley KS, …, Dougan G, Salmond GP (2013)
BMC Genomics 14: 822
A comparison of dense transposon insertion libraries in the Salmonella serovars Typhi and Typhimurium
Barquist L, Langridge GC, Turner DJ, Phan M, Turner AK, Bateman A, Parkhill J, Wain J, Gardner PP (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 NJ, Mitchell AM, Gould KA, Inverarity D, Barquist L, Feltwell T, Fookes MC, Harris SR, Dordel J, Salter SJ, …, Mitchell TJ, Bentley SD (2013)
PLOS Genetics 9 (10): 10038
The agr locus regulates virulence and colonization genes in Clostridium difficile 027
Martin MJ, Clare S, Goulding D, Faulds-Pain A, Barquist L, Browne HP, Pettit LJ, Dougan G, Lawley TD, Wren BW (2013)
Journal of Bacteriology 195 (16): 3672-81
Approaches to querying bacterial genomes with transposon-insertion sequencing
Barquist L, Boinett CJ, Cain AK (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 RA, Kay S, Connor T, Barquist L, Sait L, Holt KE, Sivaraman K, Wileman TM, 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 VK, Pickard DJ, Barquist L, Sivaraman K, Page AJ, Hart PJ, Arends MJ, Holt KE, Kane L, Mottram LF, …, Kingsley RA, Dougan G (2013)
PLOS One 8 (12): 84567
2012
A high-resolution view of genome-wide pneumococcal transformation
Croucher NJ, Harris SR, Barquist L, Parkhill J, Bentley SD (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 PP, Barquist L, Bateman A, Nawrocki EP, Weinberg Z (2011)
Nucleic Acids Research 39 (14): 5845-52
2009
Evolutionary modeling and prediction of non-coding RNAs in Drosophila
Bradley RK, Uzilov AV, Skinner ME, Bendana YR, 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-