Imperial College London

ProfessorZoltanTakats

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Analytical Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 2760z.takats

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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228 results found

Peruzzotti-Jametti L, Willis CM, Krzak G, Hamel R, Pirvan L, Ionescu R-B, Reisz JA, Prag HA, Garcia-Segura ME, Wu V, Xiang Y, Barlas B, Casey AM, van den Bosch AMR, Nicaise AM, Roth L, Bates GR, Huang H, Prasad P, Vincent AE, Frezza C, Viscomi C, Balmus G, Takats Z, Marioni JC, D'Alessandro A, Murphy MP, Mohorianu I, Pluchino Set al., 2024, Mitochondrial complex I activity in microglia sustains neuroinflammation., Nature, Vol: 628, Pages: 195-203

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Journal article

Dorado E, Doria ML, Nagelkerke A, McKenzie JS, Maneta-Stavrakaki S, Whittaker TE, Nicholson JK, Coombes RC, Stevens MM, Takats Zet al., 2024, Extracellular vesicles as a promising source of lipid biomarkers for breast cancer detection in blood plasma., J Extracell Vesicles, Vol: 13

Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in cancer, from development to metastasis. EV-based liquid biopsy is a promising strategy for cancer diagnosis as EVs can be found in cancer patients' body fluids. In this study, the lipid composition of breast cancer-derived EVs was studied as well as the potential of blood plasma EVs for the identification of lipid biomarkers for breast cancer detection. Initially, an untargeted lipidomic analysis was carried out for a panel of cancerous and non-cancerous mammary epithelial cells and their secreted EVs. We found that breast cancer-derived EVs are enriched in sphingolipids and glycerophospholipids compared to their parental cells. The initial in vitro study showed that EVs and their parental cells can be correctly classified (100% accuracy) between cancerous and non-cancerous, as well as into their respective breast cancer subtypes, based on their lipid composition. Subsequently, an untargeted lipidomic analysis was carried out for blood plasma EVs from women diagnosed with breast cancer (primary or progressive metastatic breast cancer) as well as healthy women. Correspondingly, when blood plasma EVs were analysed, breast cancer patients and healthy women were correctly classified with an overall accuracy of 93.1%, based on the EVs' lipid composition. Similarly, the analysis of patients with primary breast cancer and healthy women showed an overall accuracy of 95% for their correct classification. Furthermore, primary and metastatic breast cancers were correctly classified with an overall accuracy of 89.5%. This reveals that the blood plasma EVs' lipids may be a promising source of biomarkers for detection of breast cancer. Additionally, this study demonstrates the usefulness of untargeted lipidomics in the study of EV lipid composition and EV-associated biomarker discovery studies. This is a proof-of-concept study and a starting point for further analysis on the

Journal article

Abdelaziz MEMK, Zhao J, Gil Rosa B, Lee H-T, Simon D, Vyas K, Li B, Koguna H, Li Y, Demircali AA, Uvet H, Gencoglan G, Akcay A, Elriedy M, Kinross J, Dasgupta R, Takats Z, Yeatman E, Yang G-Z, Temelkuran Bet al., 2024, Fiberbots: Robotic fibers for high-precision minimally invasive surgery, Science Advances, Vol: 10, ISSN: 2375-2548

Precise manipulation of flexible surgical tools is crucial in minimally invasive surgical procedures, necessitating a miniature and flexible robotic probe that can precisely direct the surgical instruments. In this work, we developed a polymer-based robotic fiber with a thermal actuation mechanism by local heating along the sides of a single fiber. The fiber robot was fabricated by highly scalable fiber drawing technology using common low-cost materials. This low-profile (below 2 millimeters in diameter) robotic fiber exhibits remarkable motion precision (below 50 micrometers) and repeatability. We developed control algorithms coupling the robot with endoscopic instruments, demonstrating high-resolution in situ molecular and morphological tissue mapping. We assess its practicality and safety during in vivo laparoscopic surgery on a porcine model. High-precision motion of the fiber robot delivered endoscopically facilitates the effective use of cellular-level intraoperative tissue identification and ablation technologies, potentially enabling precise removal of cancer in challenging surgical sites.

Journal article

Manoli E, Higginson J, Tolley N, Darzi A, Kinross J, Temelkuran B, Takats Zet al., 2024, Human robotic surgery with intraoperative tissue identification using rapid evaporation ionisation mass spectrometry, Scientific Reports, Vol: 14, ISSN: 2045-2322

Instantaneous, continuous, and reliable information on the molecular biology of surgical target tissue could significantly contribute to the precision, safety, and speed of the intervention. In this work, we introduced a methodology for chemical tissue identification in robotic surgery using rapid evaporative ionisation mass spectrometry. We developed a surgical aerosol evacuation system that is compatible with a robotic platform enabling consistent intraoperative sample collection and assessed the feasibility of this platform during head and neck surgical cases, using two different surgical energy devices. Our data showed specific, characteristic lipid profiles associated with the tissue type including various ceramides, glycerophospholipids, and glycerolipids, as well as different ion formation mechanisms based on the energy device used. This platform allows continuous and accurate intraoperative mass spectrometry-based identification of ablated/resected tissue and in combination with robotic registration of images, time, and anatomical positions can improve the current robot-assisted surgical platforms and guide surgical strategy.

Journal article

Kreuzaler P, Inglese P, Ghanate A, Gjelaj E, Wu V, Panina Y, Mendez-Lucas A, MacLachlan C, Patani N, Hubert CB, Huang H, Greenidge G, Rueda OM, Taylor AJ, Karali E, Kazanc E, Spicer A, Dexter A, Lin W, Thompson D, Silva Dos Santos M, Calvani E, Legrave N, Ellis JK, Greenwood W, Green M, Nye E, Still E, CRUK Rosetta Grand Challenge Consortium, Barry S, Goodwin RJA, Bruna A, Caldas C, MacRae J, de Carvalho LPS, Poulogiannis G, McMahon G, Takats Z, Bunch J, Yuneva Met al., 2023, Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer., Nat Metab, Vol: 5, Pages: 1870-1886

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Journal article

Kowalka AM, Alexiadou K, Cuenco J, Clarke REE, Minnion J, Williams ELL, Bech P, Purkayastha S, Ahmed ARR, Takats Z, Whitwell HJJ, Romero MG, Bloom SRR, Camuzeaux S, Lewis MRR, Khoo B, Tan TM-Met al., 2023, The postprandial secretion of peptide YY<sub>1-36</sub> and <sub>3-36</sub> in obesity is differentially increased after gastric bypass versus sleeve gastrectomy, CLINICAL ENDOCRINOLOGY, Vol: 99, Pages: 272-284, ISSN: 0300-0664

Journal article

Voorde JV, Steven RT, Najumudeen AK, Ford CA, Dexter A, Gonzalez-Fernandez A, Nikula CJ, Xiang Y, Ford L, Stavrakaki SM, Gilroy K, Zeiger LB, Pennel K, Hatthakarnkul P, Elia EA, Nasif A, Murta T, Manoli E, Mason S, Gillespie M, Lannagan TRM, Vlahov N, Ridgway RA, Nixon C, Raven A, Mills M, Athineos D, Kanellos G, Nourse C, Gay DM, Hughes M, Burton A, Yan B, Sellers K, Wu V, De Ridder K, Shokry E, Uribe AH, Clark W, Clark G, Kirschner K, Thienpont B, Li VSW, Maddocks ODK, Barry ST, Goodwin RJA, Kinross J, Edwards J, Yuneva MO, Sumpton D, Takats Z, Campbell AD, Bunch J, Sansom OJet al., 2023, Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target, NATURE METABOLISM, Vol: 5, Pages: 1303-+

Journal article

Higginson JA, Breik O, Thompson AH, Ashrafian H, Hardman JC, Takats Z, Paleri V, Dhanda Jet al., 2023, Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: a meta-analysis, Oral Oncology, Vol: 142, Pages: 1-13, ISSN: 1368-8375

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.

Journal article

Green FM, Castellani ME, Jia Y, Eyres A, Smith N, Thompson S, Blenkinsopp P, Burt M, Vallance C, Bunch J, Takats Z, Brouard Met al., 2023, Development of High Throughput Microscope Mode Secondary Ion Mass Spectrometry Imaging, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 34, Pages: 1272-1282, ISSN: 1044-0305

Journal article

Jiwa N, Ford L, Roberts D, Danckert N, Marchesi J, Leff D, Takats Zet al., 2023, Identification of Nipple Biofluid Analytes by Desorption Electrospray Ionization (DESI) Mass Spectrometry and Its Interaction with the Nipple Fluid Microbiota, 24th Annual Meeting of The American Society of Breast Surgeons (ASBrS), Publisher: SPRINGER, Pages: S550-S551, ISSN: 1068-9265

Conference paper

Kowalka AMM, Alexiadou K, Cuenco J, Clarke REE, Camuzeaux S, Minnion J, Williams ELL, Bech P, Purkayastha S, Ahmed ARR, Takats Z, Khoo B, Whitwell HJJ, Romero MGG, Bloom SRR, Lewis MRR, Tan TM-Met al., 2023, Commentary on "The road to reliable peptide assays is paved with good guidelines", CLINICAL ENDOCRINOLOGY, Vol: 98, Pages: 763-765, ISSN: 0300-0664

Journal article

Xiang Y, Metodiev M, Wang M, Cao B, Bunch J, Takats Zet al., 2023, Enhancement of ambient mass spectrometry imaging data by image restoration, Metabolites, Vol: 13, Pages: 1-16, ISSN: 2218-1989

Mass spectrometry imaging (MSI) has been a key driver of groundbreaking discoveries in a number of fields since its inception more than 50 years ago. Recently, MSI development trends have shifted towards ambient MSI (AMSI) as the removal of sample-preparation steps and the possibility of analysing biological specimens in their natural state have drawn the attention of multiple groups across the world. Nevertheless, the lack of spatial resolution has been cited as one of the main limitations of AMSI. While significant research effort has presented hardware solutions for improving the resolution, software solutions are often overlooked, although they can usually be applied in a cost-effective manner after image acquisition. In this vein, we present two computational methods that we have developed to directly enhance the image resolution post-acquisition. Robust and quantitative resolution improvement is demonstrated for 12 cases of openly accessible datasets across laboratories around the globe. Using the same universally applicable Fourier imaging model, we discuss the possibility of true super-resolution by software for future studies.

Journal article

Alexander J, Posma J, Scott A, Poynter L, Mason S, Herendi L, Roberts L, McDonald J, Cameron S, Darzi A, Goldin R, Takats Z, Marchesi J, Teare J, Kinross Jet al., 2023, Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer, Microbiome, Vol: 11, Pages: 1-14, ISSN: 2049-2618

Background and aimsThe gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.MethodsA multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.ResultsThirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10−11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR&

Journal article

Dannhorn A, Doria ML, McKenzie J, Inglese P, Swales JGG, Hamm G, Strittmatter N, Maglennon G, Ghaem-Maghami S, Goodwin RJA, Takats Zet al., 2023, Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies, METABOLITES, Vol: 13

Journal article

Nagy I, Friston D, Cuddihy J, Luiz J, Truong A, Laptin H, Meirvaan B, Peter S, Orsolya O, Joao V, Tim M, Sini J, Helen L, Declan C, Marcela V, Attila G, Zoltan T, Gabor J, Elizabeth Wet al., 2023, Elevated 18:0 lysophosphatidylcholine contributes to the development of pain in tissue injury, Pain, Vol: 164, Pages: e103-e115, ISSN: 0304-3959

Tissue injuries, including burns, are major causes of death and morbidity worldwide. These injuries result in the release of intracellular molecules and subsequent inflammatory reactions, changing the tissues’ chemical milieu and leading to the development of persistent pain through activating pain-sensing primary sensory neurons. However, the majority of pain-inducing agents in injured tissues are unknown. Here, we report that, amongst other important metabolite changes, lysophosphatidylcholines (LPCs) including 18:0 LPC exhibit significant and consistent local burn injury-induced changes in concentration. 18:0 LPC induces immediate pain and the development of hypersensitivities to mechanical and heat stimuli through molecules including the transient receptor potential ion channel, vanilloid sub-family, member 1 and member 2 at least partly via increasing lateral pressure in the membrane. As levels of LPCs including 18:0 LPC increase in other tissue injuries, our data reveal a novel role for these lipids in injury-associated pain. These findings have high potential to improve patient care.

Journal article

Marcus D, Phelps DL, Savage A, Balog J, Kudo H, Dina R, Bodai Z, Rosini F, Ip J, Amgheib A, Abda J, Manoli E, McKenzie J, Yazbek J, Takats Z, Ghaem-Maghami Set al., 2022, Point-of-care diagnosis of endometrial cancer using the surgical intelligent knife (iknife)-a prospective pilot study of diagnostic accuracy, Cancers, Vol: 14, Pages: 1-14, ISSN: 2072-6694

Introduction: Delays in the diagnosis and treatment of endometrial cancer negatively impact patient survival. The aim of this study was to establish whether rapid evaporative ionisation mass spectrometry using the iKnife can accurately distinguish between normal and malignant endometrial biopsy tissue samples in real time, enabling point-of-care (POC) diagnoses. Methods: Pipelle biopsy samples were obtained from consecutive women needing biopsies for clinical reasons. A Waters G2-XS Xevo Q-Tof mass spectrometer was used in conjunction with a modified handheld diathermy (collectively called the ‘iKnife’). Each tissue sample was processed with diathermy, and the resultant surgical aerosol containing ionic lipid species was then analysed, producing spectra. Principal component analyses and linear discriminant analyses were performed to determine variance in spectral signatures. Leave-one-patient-out cross-validation was used to test the diagnostic accuracy. Results: One hundred and fifty patients provided Pipelle biopsy samples (85 normal, 59 malignant, 4 hyperplasia and 2 insufficient), yielding 453 spectra. The iKnife differentiated between normal and malignant endometrial tissues on the basis of differential phospholipid spectra. Cross-validation revealed a diagnostic accuracy of 89% with sensitivity, specificity, positive predictive value and negative predictive value of 85%, 93%, 94% and 85%, respectively. Conclusions: This study is the first to use the iKnife to identify cancer in endometrial Pipelle biopsy samples. These results are highly encouraging and suggest that the iKnife could be used in the clinic to provide a POC diagnosis.

Journal article

Patel P, Kumar S, Doria L, Soares R, Abbassi-Ghadi N, Takats Z, Hanna Get al., 2022, The clinical utilisation of tissue imaging Mass Spectrometry as a diagnostic model for Oesophageal Adenocarcinoma, AUGIS Annual Scientific Meeting, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323

Conference paper

Dannhorn A, Swales JG, Hamm G, Strittmatter N, Kudo H, Maglennon G, Goodwin RJA, Takats Zet al., 2022, Evaluation of Formalin-Fixed and FFPE Tissues for Spatially Resolved Metabolomics and Drug Distribution Studies, PHARMACEUTICALS, Vol: 15

Journal article

Kaufmann M, Vaysse P-M, Savage A, Amgheib A, Marton A, Manoli E, Fichtinger G, Pringle SD, Rudan JF, Heeren RMA, Takats Z, Balog J, Siegel TPet al., 2022, Harmonization of Rapid Evaporative Ionization Mass Spectrometry Workflows across Four Sites and Testing Using Reference Material and Local Food-Grade Meats, METABOLITES, Vol: 12

Journal article

Steven RT, Niehaus M, Taylor AJ, Nasif A, Elia E, Goodwin RJA, Takats Z, Bunch Jet al., 2022, Atmospheric-Pressure Infrared Laser-Ablation Plasma- Postionization Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded (FFPE) and Fresh-Frozen Tissue Sections with No Sample Preparation, ANALYTICAL CHEMISTRY, Vol: 94, Pages: 9970-9974, ISSN: 0003-2700

Journal article

Wu V, Tillner J, Jones E, McKenzie JS, Gurung D, Mroz A, Poynter L, Simon D, Grau C, Altafaj X, Dumas M-E, Gilmore I, Bunch J, Takats Zet al., 2022, High resolution ambient MS imaging of biological samples by desorption electro-flow focussing ionization, Analytical Chemistry, Vol: 94, Pages: 10035-10044, ISSN: 0003-2700

In this study, we examine the suitability of desorption electro-flow focusing ionization (DEFFI) for mass spectrometry imaging (MSI) of biological tissue. We also compare the performance of desorption electrospray ionization (DESI) with and without the flow focusing setup. The main potential advantages of applying the flow focusing mechanism in DESI is its rotationally symmetric electrospray jet, higher intensity, more controllable parameters, and better portability due to the robustness of the sprayer. The parameters for DEFFI have therefore been thoroughly optimized, primarily for spatial resolution but also for intensity. Once the parameters have been optimized, DEFFI produces similar images to the existing DESI. MS images for mouse brain samples, acquired at a nominal pixel size of 50 μm, are comparable for both DESI setups, albeit the new sprayer design yields better sensitivity. Furthermore, the two methods are compared with regard to spectral intensity as well as the area of the desorbed crater on rhodamine-coated slides. Overall, the implementation of a flow focusing mechanism in DESI is shown to be highly suitable for imaging biological tissue and has potential to overcome some of the shortcomings experienced with the current geometrical design of DESI.

Journal article

Sani M, Ford L, Simon D, Xiang Y, McKenzie J, Stavrakaki SM, Paizs P, Huq T, Higginson J, Alexander J, Takats Z, Kinross Jet al., 2022, A prospective pilot study of desorption electrospray ionisation mass spectrometry (DESI-MS) for the early detection of colorectal adenoma., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Paizs P, Roberts D, Danckert N, Lewis J, Sani M, Jamroziak M, Goldin R, Marchesi J, Ford L, Alexander J, Takats Z, Kinross Jet al., 2022, Gut microbial co-metabolism influences the tumor microenvironment, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Correia GDS, Takis PG, Sands CJ, Kowalka AM, Tan T, Turtle L, Ho A, Semple MG, Openshaw PJM, Baillie JK, Takáts Z, Lewis MRet al., 2022, 1H NMR Signals from urine excreted protein are a source of bias in probabilistic quotient normalization, Analytical Chemistry, Vol: 94, Pages: 6919-6923, ISSN: 0003-2700

Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared across a large proportion of the spectral profile (>50%). Where 1H nuclear magnetic resonance (NMR) spectroscopy is employed, the presence of urinary protein can elevate the spectral baseline and substantially impact the resulting profile. Using 1H NMR profile measurements of spot urine samples collected from hospitalized COVID-19 patients in the ISARIC 4C study, we determined that PQN coefficients are significantly correlated with observed protein levels (r2 = 0.423, p < 2.2 × 10–16). This correlation was significantly reduced (r2 = 0.163, p < 2.2 × 10–16) when using a computational method for suppression of macromolecular signals known as small molecule enhancement spectroscopy (SMolESY) for proteinic baseline removal prior to PQN. These results highlight proteinuria as a common yet overlooked source of bias in 1H NMR metabolic profiling studies which can be effectively mitigated using SMolESY or other macromolecular signal suppression methods before estimation of normalization coefficients.

Journal article

Paizs P, Mullish BH, Alexander JL, Maneta-Stavrakaki S, Sani M, Ford L, Monaghan T, Kinross JM, McDonald JA, Kao DH, Marchesi J, Takats Zet al., 2022, INTESTINAL MICROBIOTA TRANSPLANT FOR RECURRENT <i>CLOSTRIODIOIDES</i> <i>DIFFICILE</i> INFECTION IS ASSOCIATED WITH RESTORATION OF MICROBIAL ARYLSULFATASES AND SULFATIDE DEGRADATION, GASTROENTEROLOGY, Vol: 162, Pages: S649-S649, ISSN: 0016-5085

Journal article

Jiwa N, Ezzat A, holt J, wijayatilake D, Takats Z, Leff Det al., 2022, Nipple aspirate fluid and its use for the early detection of breast cancer, Annals of Medicine and Surgery, Vol: 77, Pages: 1-6, ISSN: 2049-0801

Nipple aspirate fluid is the physiological biofluid lining ductal epithelial cells. Historically, cytology of nipple fluid has been the gold standard diagnostic method for assessment of ductal fluid in patients with symptomatic nipple discharge. The role of biomarker discovery in nipple aspirate fluid for assessment of asymptomatic and high-risk patients is highly attractive but evaluation to date is limited by poor diagnostic accuracy. However, the emergence of new technologies capable of identifying metabolites that have been previously thought unidentifiable within such small volumes of fluid, has enabled testing of nipple biofluid to be re-examined. This review evaluates the use of new technologies to evaluate the components of nipple fluid and their potential to serve as biomarkers in screening.

Journal article

Isberg OG, Giunchiglia V, McKenzie JS, Takats Z, Jonasson JG, Bodvarsdottir SK, Thorsteinsdottir M, Xiang Yet al., 2022, Automated Cancer Diagnostics via Analysis of Optical and Chemical Images by Deep and Shallow Learning, METABOLITES, Vol: 12

Journal article

Inglese P, Huang HX, Wu V, Lewis MR, Takats Zet al., 2022, Mass recalibration for desorption electrospray ionization mass spectrometry imaging using endogenous reference ions, BMC Bioinformatics, Vol: 23, Pages: 1-17, ISSN: 1471-2105

BackgroundMass spectrometry imaging (MSI) data often consist of tens of thousands of mass spectra collected from a sample surface. During the time necessary to perform a single acquisition, it is likely that uncontrollable factors alter the validity of the initial mass calibration of the instrument, resulting in mass errors of magnitude significantly larger than their theoretical values. This phenomenon has a two-fold detrimental effect: (a) it reduces the ability to interpret the results based on the observed signals, (b) it can affect the quality of the observed signal spatial distributions.ResultsWe present a post-acquisition computational method capable of reducing the observed mass drift by up to 60 ppm in biological samples, exploiting the presence of typical molecules with a known mass-to-charge ratio. The procedure, tested on time-of-flight and Orbitrap mass spectrometry analyzers interfaced to a desorption electrospray ionization (DESI) source, improves the molecular annotation quality and the spatial distributions of the detected ions.ConclusionThe presented method represents a robust and accurate tool for performing post-acquisition mass recalibration of DESI-MSI datasets and can help to increase the reliability of the molecular assignment and the data quality.

Journal article

Mehta R, Chekmeneva E, Jackson H, Sands C, Mills E, Arancon D, Li HK, Arkell P, Rawson T, Hammond R, Amran M, Haber A, Cooke G, Noursadeghi M, Kaforou M, Lewis M, Takats Z, Sriskandan Set al., 2022, Antiviral metabolite 3’-Deoxy-3’,4’-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19, Med, Vol: 3, Pages: 204-215.e6, ISSN: 2666-6340

Background:There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing.Methods:Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with viral infections including COVID-19, bacterial infections, inflammatory conditions, and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings. Associations between whole-blood gene expression and the identified metabolite of interest were examined.Findings:3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), was detected for the first time in serum. When comparing 60 viral to 101 non-viral cases in the discovery cohort, ddhC was the most differentially abundant metabolite, generating an area under the receiver operating characteristic curve (AUC) of 0.954 (95% CI: 0.923-0.986). In the validation cohort, ddhC was again the most significantly differentially abundant metabolite when comparing 40 viral to 40 bacterial cases, generating an AUC of 0.81 (95% CI 0.708-0.915). Transcripts of viperin and CMPK2, enzymes responsible for ddhCTP synthesis, were amongst the five genes most highly correlated to ddhC abundance.Conclusions:The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes viperin and CMPK2 are implicated in ddhC production in vivo. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness, and acute infection management.

Journal article

Dannhorn A, Kazanc E, Hamm G, Swales JG, Strittmatter N, Maglennon G, Goodwin RJA, Takats Zet al., 2022, Correlating Mass Spectrometry Imaging and Liquid Chromatography-Tandem Mass Spectrometry for Tissue-Based Pharmacokinetic Studies, METABOLITES, Vol: 12

Journal article

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