Imperial College London

DrLachlanCoin

Faculty of MedicineDepartment of Infectious Disease

Honorary Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 1930l.coin

 
 
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Location

 

172Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

142 results found

Gliddon H, Kaforou M, Alikian M, Coote D, Zhou C, Oni T, Anderson ST, Brent AJ, Crampin AC, Eley B, Heyderman R, Langford PR, Kern F, Ottenhoff THM, Hibberd ML, French N, Wright V, Dockrell HM, Coin L, Wilkinson R, Levin Met al., 2021, Identification of reduced host transcriptomic signatures for tuberculosis disease and digital PCR-based validation and quantification, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224

Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were further investigated using reverse transcriptase (RT)—digital PCR (dPCR). A four-transcript signature (GBP6, TMCC1, PRDM1, and ARG1) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI95% 82.2–100%). A three-transcript signature (FCGR1A, ZNF296, and C1QB) differentiated TB from LTBI (AUC 97.3%, CI95%: 93.3–100%), regardless of HIV. These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.

Journal article

Nguyen SH, Cao MD, Coin LJM, 2021, Real-time resolution of short-read assembly graph using ONT long reads, PLOS COMPUTATIONAL BIOLOGY, Vol: 17, ISSN: 1553-734X

Journal article

Murigneux V, Rai SK, Furtado A, Bruxner TJC, Tian W, Harliwong I, Wei H, Yang B, Ye Q, Anderson E, Mao Q, Drmanac R, Wang O, Peters BA, Xu M, Wu P, Topp B, Coin LJM, Henry RJet al., 2020, Comparison of long-read methods for sequencing and assembly of a plant genome, GIGASCIENCE, Vol: 9, ISSN: 2047-217X

Journal article

Borghesi A, Trück J, Asgari S, Sancho-Shimizu V, Agyeman PKA, Bellos E, Giannoni E, Stocker M, Posfay-Barbe KM, Heininger U, Bernhard-Stirnemann S, Niederer-Loher A, Kahlert CR, Natalucci G, Relly C, Riedel T, Kuehni CE, Thorball CW, Chaturvedi N, Martinon-Torres F, Kuijpers TW, Coin L, Wright V, Herberg J, Levin M, Aebi C, Berger C, Fellay J, Schlapbach LJ, EUCLIDS consortium and the Swiss Paediatric Sepsis Studyet al., 2020, Whole-exome sequencing for the identification of rare variants in primary immunodeficiency genes in children with sepsis - a prospective population-based cohort study., Clinical Infectious Diseases, Vol: 71, Pages: e614-e623, ISSN: 1058-4838

BACKGROUND: The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes. METHODS: Multicenter population-based prospective study including previously healthy children ≥28 days and <17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported. RESULTS: 176 children presenting with 185 sepsis episodes underwent WES (median age 52 months, IQR 15.4-126.4). 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) were found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants which were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants. CONCLUSIONS: Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected Variants of Uncertain Significance in PID genes in one out of five children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.

Journal article

Zhou C, Olukolu B, Gemenet DC, Wu S, Gruneberg W, Cao MD, Fei Z, Zeng Z-B, George AW, Khan A, Yencho GC, Coin LJMet al., 2020, Assembly of whole-chromosome pseudomolecules for polyploid plant genomes using outbred mapping populations, NATURE GENETICS, Vol: 52, Pages: 1256-+, ISSN: 1061-4036

Journal article

Pitt ME, Nguyen SH, Duarte TPS, Roddam LF, Blaskovich MAT, Cooper MA, Coin LJMet al., 2020, Complete Genome Sequences of Clinical Pandoraea fibrosis Isolates, MICROBIOLOGY RESOURCE ANNOUNCEMENTS, Vol: 9, ISSN: 2576-098X

Journal article

Pitt ME, Nguyen SH, Duarte TPS, Teng H, Blaskovich MAT, Cooper MA, Coin LJMet al., 2020, Evaluating the genome and resistome of extensively drug-resistant Klebsiella pneumoniae using native DNA and RNA Nanopore sequencing, GIGASCIENCE, Vol: 9, ISSN: 2047-217X

Journal article

Zhang P, Ganesamoorthy D, Nguyen SH, Au R, Coin LJ, Tey S-Ket al., 2020, Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy, JOURNAL FOR IMMUNOTHERAPY OF CANCER, Vol: 8

Journal article

Gemenet DC, Pereira GDS, De Boeck B, Wood JC, Mollinari M, Olukolu BA, Diaz F, Mosquera V, Ssali RT, David M, Kitavi MN, Burgos G, Zum Felde T, Ghislain M, Carey E, Swanckaert J, Coin LJM, Fei Z, Hamilton JP, Yada B, Yencho GC, Zeng Z-B, Mwanga ROM, Khan A, Gruneberg WJ, Buell CRet al., 2020, Quantitative trait loci and differential gene expression analyses reveal the genetic basis for negatively associated beta-carotene and starch content in hexaploid sweetpotato [Ipomoea batatas (L.) Lam.], THEORETICAL AND APPLIED GENETICS, Vol: 133, Pages: 23-36, ISSN: 0040-5752

Journal article

Raftery LJ, Howard CB, Grewal YS, Vaidyanathan R, Jones ML, Anderson W, Korbie D, Duarte T, Minh DC, Son HN, Coin LJM, Mahler SM, Trau Met al., 2019, Retooling phage display with electrohydrodynamic nanomixing and nanopore sequencing, LAB ON A CHIP, Vol: 19, Pages: 4083-4092, ISSN: 1473-0197

Journal article

Xu J, Falconer C, Nguyen Q, Crawford J, McKinnon BD, Mortlock S, Senabouth A, Andersen S, Chiu HS, Jiang L, Palpant NJ, Yang J, Mueller MD, Hewitt AW, Pebay A, Montgomery GW, Powell JE, Coin LJMet al., 2019, Genotype-free demultiplexing of pooled single-cell RNA-seq, GENOME BIOLOGY, Vol: 20, ISSN: 1474-760X

Journal article

Wang X, Nijman R, Camuzeaux S, Sands C, Jackson H, Kaforou M, Emonts M, Herberg J, Maconochie I, Carrol E, Paulus S, Zenz W, Coin L, Flier MVD, Groot RD, Martinon-Torres F, Schlapbach LJ, Pollard A, Fink C, Kuijpers TT, Anderson S, Lewis M, Levin M, McClure M, EUCLIDS consortiumet al., 2019, Plasma lipid profiles discriminate bacterial from viral infection in febrile children, Scientific Reports, Vol: 9, ISSN: 2045-2322

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The ‘omics’ approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n=20) and confirmed viral infection (n=20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group..A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.

Journal article

Alves AC, De Silva NMG, Karhunen V, Sovio U, Das S, Rob Taal H, Warrington NM, Lewin AM, Kaakinen M, Cousminer DL, Thiering E, Timpson NJ, Bond TA, Lowry E, Brown CD, Estivill X, Lindi V, Bradfield JP, Geller F, Speed D, Coin LJM, Loh M, Barton SJ, Beilin LJ, Bisgaard H, Bønnelykke K, Alili R, Hatoum IJ, Schramm K, Cartwright R, Charles MA, Salerno V, Clément K, Claringbould AAJ, Van Duijn CM, Moltchanova E, Eriksson JG, Elks C, Feenstra B, Flexeder C, Franks S, Frayling TM, Freathy RM, Elliott P, Widén E, Hakonarson H, Hattersley AT, Rodriguez A, Banterle M, Heinrich J, Heude B, Holloway JW, Hofman A, Hyppönen E, Inskip H, Kaplan LM, Hedman AK, Läärä E, Prokisch H, Grallert H, Lakka TA, Lawlor DA, Melbye M, Ahluwalia TS, Marinelli M, Millwood IY, Palmer LJ, Pennell CE, Perry JR, Ring SM, Savolainen MJ, Rivadeneira F, Standl M, Sunyer J, Tiesler CMT, Uitterlinden AG, Schierding W, Sullivan OM, Prokopenko I, Herzig KH, Smith GD, O'Reilly P, Felix JF, Buxton JL, Blakemore AIF, Ong KK, Jaddoe VWV, Grant SFA, Sebert S, McCarthy MI, Järvelin MRet al., 2019, GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI, Science Advances, Vol: 5, ISSN: 2375-2548

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here we combine genome-wide association studies with modelling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score and co-localization analyses to determine how developmental timings, molecular pathways and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult BMI, with variants associated with adult BMI acting as early as 4-6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Journal article

Shimizu C, Kim J, Eleftherohorinou H, Wright VJ, Hoang LT, Tremoulet AH, Franco A, Hibberd ML, Takahashi A, Kubo M, Ito K, Tanaka T, Onouchi Y, Coin LJM, Levin M, Burns JC, Shike H, International Kawasaki Disease Genetic Consortiumet al., 2019, HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease, Human Immunology, Vol: 80, Pages: 731-738, ISSN: 0198-8859

Kawasaki disease (KD) is a pediatric vasculitis caused by an unknown trigger in genetically susceptible children. The incidence varies widely across genetically diverse populations. Several associations with HLA Class I alleles have been reported in single cohort studies. Using a genetic approach, from the nine single nucleotide variants (SNVs) associated with KD susceptibility in children of European descent, we identified SNVs near the HLA-C (rs6906846) and HLA-B genes (rs2254556) whose association was replicated in a Japanese descent cohort (rs6906846 p = 0.01, rs2254556 p = 0.005). The risk allele (A at rs6906846) was also associated with HLA-C*07:02 and HLA-C*04:01 in both US multi-ethnic and Japanese cohorts and HLA-C*12:02 only in the Japanese cohort. The risk A-allele was associated with eight non-conservative amino acid substitutions (amino acid positions); Asp or Ser (9), Arg (14), Ala (49), Ala (73), Ala (90), Arg (97), Phe or Ser (99), and Phe or Ser (116) in the HLA-C peptide binding groove that binds peptides for presentation to cytotoxic T cells (CTL). This raises the possibility of increased affinity to a "KD peptide" that contributes to the vasculitis of KD in genetically susceptible children.

Journal article

Bialasiewicz S, Duarte TPS, Nguyen SH, Sukumaran V, Stewart A, Appleton S, Pitt ME, Bainomugisa A, Jennison AV, Graham R, Coin LJM, Hajkowicz Ket al., 2019, Rapid diagnosis of Capnocytophaga canimorsus septic shock in an immunocompetent individual using real-time Nanopore sequencing: a case report, BMC INFECTIOUS DISEASES, Vol: 19, ISSN: 1471-2334

Journal article

Reed AEM, Lal S, Kutasovic JR, Wockner L, Robertson A, de Luca XM, Kalita-de Croft P, Dalley AJ, Coorey CP, Kuo L, Ferguson K, Niland C, Miller G, Johnson J, Reid LE, Males R, Saunus JM, Chenevix-Trench G, Coin L, Lakhani SR, Simpson PTet al., 2019, LobSig is a multigene predictor of outcome in invasive lobular carcinoma, NPJ BREAST CANCER, Vol: 5

Journal article

Georgiadou A, Lee HJ, Walther M, van Beek A, Fitriani F, Wouters D, Kuijpers T, Nwakanma D, D'Alessandro U, Riley E, Otto T, Ghani A, Levin M, Coin L, Conway D, Bretscher M, Cunnington Aet al., 2019, Modelling pathogen load dynamics to elucidate mechanistic determinants of host-Plasmodium falciparum interactions, Nature Microbiology, Vol: 4, Pages: 1592-1602, ISSN: 2058-5276

During infection, increasing pathogen load stimulates both protective and harmful aspects of the host response. The dynamics of this interaction are hard to quantify in humans, but doing so could improve understanding of mechanisms of disease and protection. We sought to model the contributions of parasite multiplication rate and host response to observed parasite load in individual subjects with Plasmodium falciparum malaria, using only data obtained at the time of clinical presentation, and then to identify their mechanistic correlates. We predicted higher parasite multiplication rates and lower host responsiveness in severe malaria cases, with severe anemia being more insidious than cerebral malaria. We predicted that parasite growth-inhibition was associated with platelet consumption, lower expression of CXCL10 and type-1 interferon-associated genes, but increased cathepsin G and matrix metallopeptidase 9 expression. We found that cathepsin G and matrix metallopeptidase 9 directly inhibit parasite invasion into erythrocytes. Parasite multiplication rate was associated with host iron availability and higher complement factor H levels, lower expression of gametocyte-associated genes but higher expression of translation-associated genes in the parasite. Our findings demonstrate the potential of using explicit modelling of pathogen load dynamics to deepen understanding of host-pathogen interactions and identify mechanistic correlates of protection.

Journal article

Borghini L, Png E, Binder A, Wright VJ, Pinnock E, de Groot R, Hazelzet J, Emonts M, Van der Flier M, Schlapbach LJ, Anderson S, Secka F, Salas A, Fink C, Carrol ED, Pollard AJ, Coin LJ, Kuijpers TW, Martinon-Torres F, Zenz W, Levin M, Hibberd ML, Davila S, Gormley S, Hamilton S, Herberg J, Hourmat B, Hoggart C, Kaforou M, Sancho-Shimizu V, Abdulla A, Agapow P, Bartlett M, Bellos E, Eleftherohorinou H, Galassini R, Inwald D, Mashbat M, Menikou S, Mustafa S, Nadel S, Rahman R, Thakker C, Bokhandi S, Power S, Barham H, Pathan N, Ridout J, White D, Thurston S, Faust S, Patel S, McCorkell J, Davies P, Cratev L, Navarra H, Carter S, Ramaiah R, Patel R, Tuffrey C, Gribbin A, McCready S, Peters M, Hardy K, Standing F, O'Neill L, Abelake E, Deep A, Nsirim E, Willis L, Young Z, Royad C, White S, Fortune PM, Hudnott P, Alvez Gonzalez F, Barral-Arca R, Cebey-Lopez M, Jose Curras-Tuala M, Garcia N, Garcia Vicente L, Gomez-Carballa A, Gomez Rial J, Grela Beiroa A, Justicia Grande A, Leborans Iglesias P, Martinez Santos AE, Martinon-Torres N, Martinon Sanchez JM, Mosquera Perez B, Obando Pacheco P, Pardo-Seco J, Pischedda S, Rivero Calle I, Rodriguez-Tenreiro C, Redondo-Collazo L, Seren Fernandez S, Porto Silva MDS, Vega A, Beatriz Reyes S, Leon Leon MC, Navarro Mingorance A, Gabaldo Barrios X, Onate Vergara E, Concha Torre A, Vivanco A, Fernandez R, Gimenez Sanchez F, Sanchez Forte M, Rojo P, Ruiz Contreras J, Palacios A, Navarro M, Alvarez Alvarez C, Jose Lozano M, Carreras E, Brio Sanagustin S, Neth O, Martinez Padilla MDC, Prieto Tato LM, Guillen S, Fernandez Silveira L, Moreno D, van Furth AMT, van der Flier M, Boeddha NP, Driessen GJA, Pajkrt D, Sanders EAM, van de Beek D, van der Ende A, Philipsen HLA, Adeel AOA, Breukels MA, Brinkman DMC, de Korte CCMM, de Vries E, de Waal WJ, Dekkers R, Dings-Lammertink A, Doedens RA, Donker AE, Dousma M, Faber TE, Gerrits GPJM, Gerver JAM, Heidema J, Homan-van der Veen J, Jacobs MAM, Jansen NJG, Kawczynski P, Klucovska K, Kneyber MCJ Ket al., 2019, Identification of regulatory variants associated with genetic susceptibility to meningococcal disease, Scientific Reports, Vol: 9, ISSN: 2045-2322

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA – a NF-kB subunit, master regulator of the response to infection – under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Journal article

Teng H, Minh DC, Hall MB, Duarte T, Wang S, Coin LJMet al., 2019, Chiron: translating nanopore raw signal directly into nucleotide sequence using deep learning (vol 7, giy037, 2018), GIGASCIENCE, Vol: 8, ISSN: 2047-217X

Journal article

Middeldorp CM, Felix JF, Mahajan A, McCarthy MI, EArly Genetics Lifecourse Epidemiology EAGLE consortium, Early Growth Genetics EGG, Rodriguez Aet al., 2019, The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects, European Journal of Epidemiology, Vol: 34, Pages: 279-300, ISSN: 0393-2990

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.

Journal article

Zhang P, Raju J, Ullah MA, Au R, Varelias A, Gartlan KH, Olver SD, Samson LD, Sturgeon E, Zomerdijk N, Avery J, Gargett T, Brown MP, Coin LJ, Ganesamoorthy D, Hutchins C, Pratt GR, Kennedy GA, Morton AJ, Curley CI, Hill GR, Tey S-Ket al., 2019, Phase I Trial of Inducible Caspase 9 T Cells in Adult Stem Cell Transplant Demonstrates Massive Clonotypic Proliferative Potential and Long-term Persistence of Transgenic T Cells, CLINICAL CANCER RESEARCH, Vol: 25, Pages: 1749-1755, ISSN: 1078-0432

Journal article

Bainomugisa A, Pandey S, Donnan E, Simpson G, Foster J, Lavu E, Hiasihri S, McBryde ES, Moke R, Vincent S, Sintchenko V, Marais BJ, Coin LJM, Coulter Cet al., 2019, Cross-Border Movement of Highly Drug-Resistant Mycobacterium tuberculosis from Papua New Guinea to Australia through Torres Strait Protected Zone, 2010-2015, EMERGING INFECTIOUS DISEASES, Vol: 25, Pages: 406-415, ISSN: 1080-6040

Journal article

Pitt ME, Minh DC, Butler MS, Ramu S, Ganesamoorthy D, Blaskovich MAT, Coin LJM, Cooper MAet al., 2019, Octapeptin C4 and polymyxin resistance occur via distinct pathways in an epidemic XDR Klebsiella pneumoniae ST258 isolate, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 74, Pages: 582-593, ISSN: 0305-7453

Journal article

Halliday A, Jain P, Hoang L, Parker R, Tolosa-Wright M, Masonou T, Green N, Boakye A, Takwoingi Y, Hamilton S, Mandagere V, Fries A, Coin L, Deeks J, White P, Levin M, Beverley P, Kon O, Lalvani Aet al., 2019, Validation of new technologies for the diagnostic evaluation of active tuberculosis (VANTDET), Efficacy and Mechanism Evaluation, ISSN: 2050-4365

Background: Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed. Objective: To validate promising new technologies (namely whole blood transcriptomics, proteomics, flow cytometry and qRT-PCR) and existing signatures for detection of active TB in samples obtained from individuals suspected of active TB. Design: Four sub-studies, each of which used the samples from biobank collected as part of the IDEA study, which was a prospective cohort of patients recruited with suspected TB. Setting: secondary care Participants: Adults (aged ≥ 16 years old) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. Interventions: New tests using either: genome-wide gene expression microarray (transcriptomics); SELDI TOF/ LC-MS (proteomics), flow cytometry, qRT-PCR. Main outcome measures: Area under the curve (AUC), sensitivity and specificity, were calculated to determine diagnostic accuracy. Positive and negative predictive values were calculated in some cases. A decision tree model was developed to calculate the incremental costs and quality-adjusted life-years (QALYs) of changing from current practice to using the novels tests. Results: The project and 4 sub-studies which assessed the previous published signatures measured using each of the new technologies, and a health economic analysis where the best performing tests were evaluated for cost effectiveness. The diagnostic accuracy of the transcriptomic tests ranged from AUC=0.81-0.84 for detecting all TB in our cohort. The performance for detecting culture confirmed TB or pulmonary TB (PTB) was better than for highly probable TB or extrapulmonary TB (EPTB) respectively, but not high enough to be clinically useful. None of the previously described serum proteomic signatures for active TB provided good diagnostic accuracy, not did the candidate rule-out tests. Four of six previously described cell

Journal article

Lu J, Wang Y, Li J, Mao L, Nguyen SH, Duarte T, Coin L, Bond P, Yuan Z, Guo Jet al., 2018, Triclosan at environmentally relevant concentrations promotes horizontal transfer of multidrug resistance genes within and across bacterial genera, ENVIRONMENT INTERNATIONAL, Vol: 121, Pages: 1217-1226, ISSN: 0160-4120

Journal article

Shao H, Zhou C, Minh DC, Coin LJMet al., 2018, Ongoing human chromosome end extension revealed by analysis of BioNano and nanopore data, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322

Journal article

Wu S, Lau KH, Cao Q, Hamilton JP, Sun H, Zhou C, Eserman L, Gemenet DC, Olukolu BA, Wang H, Crisovan E, Godden GT, Jiao C, Wang X, Kitavi M, Manrique-Carpintero N, Vaillancourt B, Wiegert-Rininger K, Yang X, Bao K, Schaff J, Kreuze J, Gruneberg W, Khan A, Ghislain M, Ma D, Jiang J, Mwanga ROM, Leebens-Mack J, Coin LJM, Yencho GC, Buell CR, Fei Zet al., 2018, Genome sequences of two diploid wild relatives of cultivated sweetpotato reveal targets for genetic improvement, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

Journal article

Wright V, Herberg J, Kaforou M, Shimizu C, Eleftherohorinou H, Shailes H, Barendregt A, Menikou S, Gormley S, Berk M, Hoang L, Tremoulet A, Kanegaye J, Coin L, Glode M, Hibberd M, Kuijpers T, Hoggart C, Burns J, Levin Met al., 2018, Diagnosis of Kawasaki disease using a minimal whole blood gene expression signature, JAMA Pediatrics, Vol: 172, Pages: 1-10, ISSN: 2168-6203

Importance There is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms. Objective To identify a whole blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions.Design Case-control discovery study groups comprising training, test, and validation groups of children with KD or comparator febrile illness. Setting Hospitals in the UK, Spain, Netherlands and USA.Participants The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, 242 bacterial or viral infections) and 55 healthy controls. The independent validation group included 130 febrile children and 102 KD patients, including 72 in the first 7 days of illness.Exposures Whole blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (Parallel Deterministic Model Search).Main outcomes and measures The ability of transcript signatures - implemented as Disease Risk Scores - to discriminate KD cases from controls, was assessed by Area Under the Curve (AUC), sensitivity, and specificity at the optimal cut-point according to Youden’s index. Results A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set with AUC, sensitivity, and specificity (95% confidence intervals (CI)) of 96.2% (92.5-99.9), 81.7% (60.0-94.8), and 92.1% (84.0-97.0), respectively. In the validation set, the signature distinguished KD from febrile controls with AUC, sensitivity, and specificity (95% CI) of 94.6% (91.3-98.0), 85.9% (76.8-92.6), and 89.1% (83.0-93.7) respectively. The signature was applied to clinically defin

Journal article

Lu J, Jin M, Son HN, Mao L, Li J, Coin LJM, Yuan Z, Guo Jet al., 2018, Non-antibiotic antimicrobial triclosan induces multiple antibiotic resistance through genetic mutation, ENVIRONMENT INTERNATIONAL, Vol: 118, Pages: 257-265, ISSN: 0160-4120

Journal article

Ganesamoorthy D, Minh DC, Duarte T, Chen W, Coin Let al., 2018, GtTR: Bayesian estimation of absolute tandem repeat copy number using sequence capture and high throughput sequencing, BMC BIOINFORMATICS, Vol: 19, ISSN: 1471-2105

Journal article

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