Publications
228 results found
MacIntyre DA, Pruski P, Correia G, et al., 2022, Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry, Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
Jiwa N, Kumar S, Gandhewar R, et al., 2022, Diagnostic Accuracy of Nipple Discharge Fluid Cytology: A Meta-Analysis and Systematic Review of the Literature, Publisher: SPRINGER, Pages: 1774-1786, ISSN: 1068-9265
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- Citations: 2
Strittmatter N, Richards FM, Race AM, et al., 2022, Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging, ANALYTICAL CHEMISTRY, Vol: 94, Pages: 1795-1803, ISSN: 0003-2700
Wolfer AM, Correia GDS, Sands CJ, et al., 2021, peakPantheR, an R package for large-scale targeted extraction and integration of annotated metabolic features in LC-MS profiling datasets, BIOINFORMATICS, Vol: 37, Pages: 4886-4888, ISSN: 1367-4803
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- Citations: 15
Antonowicz S, Abbassi-Ghadi N, Bodai Z, et al., 2021, The smell of oesophageal adenocarcinoma: opportunities for tests and treatments, UGI Congress, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323
Strittmatter N, Kanvatirth P, Inglese P, et al., 2021, Holistic characterization of a salmonella typhimurium infection model using integrated molecular imaging., Journal of the American Society for Mass Spectrometry, Vol: 32, Pages: 2791-2802, ISSN: 1044-0305
A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Salmonella Typhimurium infection in the liver of a mouse model using the S. Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism. IMC revealed a marked increase in immune cell markers and localization in immune aggregates in infected tissues. A correlative computational method (network analysis) was deployed to find metabolic features associated with infection and revealed metabolic clusters of acetyl carnitines, as well as phosphatidylcholine and phosphatidylethanolamine plasmalogen species, which could be associated with pro-inflammatory immune cell types. By developing an IMC marker for the detection of Salmonella LPS, we were further able to identify and characterize those cell types which contained S. Typhimurium.
Metodiev MD, Steven RT, Loizeau X, et al., 2021, Modality Agnostic Model for Spatial Resolution in Mass Spectrometry Imaging: Application to MALDI MSI Data, ANALYTICAL CHEMISTRY, Vol: 93, Pages: 15295-15305, ISSN: 0003-2700
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- Citations: 4
Isberg OG, Xiang Y, Bodvarsdottir SK, et al., 2021, The effect of sample age on the metabolic information extracted from formalin-fixed and paraffin embedded tissue samples using desorption electrospray ionization mass spectrometry imaging, JOURNAL OF MASS SPECTROMETRY AND ADVANCES IN THE CLINICAL LAB, Vol: 22, Pages: 50-55, ISSN: 2667-145X
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- Citations: 5
Cuddihy J, Wu G, Ho L, et al., 2021, Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin, Scientific Reports, Vol: 11, Pages: 1-12, ISSN: 2045-2322
Burn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.
Pruski P, Dos Santos Correia G, Lewis H, et al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Plekhova V, Van Meulebroek L, De Graeve M, et al., 2021, Rapid ex vivo molecular fingerprinting of biofluids using laser-assisted rapid evaporative ionization mass spectrometry, NATURE PROTOCOLS, Vol: 16, Pages: 4327-4354, ISSN: 1754-2189
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- Citations: 6
Mason SE, Manoli E, Alexander JL, et al., 2021, Lipidomic profiling of colorectal lesions for real-time tissue recognition and risk-stratification using rapid evaporative ionisation mass spectrometry., Annals of Surgery, Vol: 00, ISSN: 0003-4932
OBJECTIVE: Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a metabolomic technique analysing tissue metabolites, which can be applied intra-operatively in real-time. The objective of this study was to profile the lipid composition of colorectal tissues using REIMS, assessing its accuracy for real-time tissue recognition and risk-stratification. SUMMARY BACKGROUND DATA: Metabolic dysregulation is a hallmark feature of carcinogenesis, however it remains unknown if this can be leveraged for real-time clinical applications in colorectal disease. METHODS: Patients undergoing colorectal resection were included, with carcinoma, adenoma and paired-normal mucosa sampled. Ex vivo analysis with REIMS was conducted using monopolar diathermy, with the aerosol aspirated into a Xevo G2S QToF mass spectrometer. Negatively charged ions over 600-1000m/z were used for univariate and multivariate functions including linear discriminant analysis. RESULTS: 161 patients were included, generating 1013 spectra. Unique lipidomic profiles exist for each tissue type, with REIMS differentiating samples of carcinoma, adenoma and normal mucosa with 93 1% accuracy and 96 1% negative predictive value for carcinoma. Neoplasia (carcinoma or adenoma) could be predicted with 96 0% accuracy and 91 8% negative predictive value. Adenomas can be risk-stratified by grade of dysplasia with 93 5% accuracy, but not histological subtype. The structure of 61 lipid metabolites was identified, revealing that during colorectal carcinogenesis there is progressive increase in relative abundance of phosphatidylglycerols, sphingomyelins and mono-unsaturated fatty acid containing phospholipids. CONCLUSIONS: The colorectal lipidome can be sampled by REIMS and leveraged for accurate real-time tissue recognition, in addition to risk-stratification of colorectal adenomas. Unique lipidomic features associated with carcinogenesis are described.
COVID-19 Host Genetics Initiative, 2021, Mapping the human genetic architecture of COVID-19, Nature, Vol: 600, Pages: 472-477, ISSN: 0028-0836
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Paizs P, Widlak M, Perdones-Montero A, et al., 2021, High-throughput fecal metabolic profiling for the early detection of colorectal cancer using a direct mass spectrometry assay., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Dorado E, Doria ML, Nagelkerke A, et al., 2021, Lipidomic analysis of extracellular vesicles and its potential for the identification of body fluid-based biomarkers for breast cancer diagnosis., Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Jiwa N, Takats Z, Leff DR, 2021, ASO Author Reflections: Diagnostic Accuracy of Nipple Aspirate Fluid Cytology in Asymptomatic Patients and Its Predictive Validity on Future Risk of Breast Cancer: A Meta-Analysis and Systematic Review of the Literature, ANNALS OF SURGICAL ONCOLOGY, Vol: 28, Pages: 3761-3762, ISSN: 1068-9265
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- Citations: 1
Cameron SJS, Perdones-Montero A, Van Meulebroek L, et al., 2021, Sample Preparation Free Mass Spectrometry Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry: Applications to Microbiology, Metabolic Biofluid Phenotyping, and Food Authenticity, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 32, Pages: 1393-1401, ISSN: 1044-0305
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- Citations: 9
Ogrinc N, Saudemont P, Takats Z, et al., 2021, Cancer Surgery 2.0: Guidance by Real-Time Molecular Technologies, TRENDS IN MOLECULAR MEDICINE, Vol: 27, Pages: 602-615, ISSN: 1471-4914
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- Citations: 18
Fala M, Somai V, Dannhorn A, et al., 2021, Comparison of <SUP>13</SUP>C MRI of hyperpolarized [1-<SUP>13</SUP>C]pyruvate and lactate with the corresponding mass spectrometry images in a murine lymphoma model, MAGNETIC RESONANCE IN MEDICINE, Vol: 85, Pages: 3027-3035, ISSN: 0740-3194
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- Citations: 6
Capece D, D'Andrea D, Begalli F, et al., 2021, Enhanced triacylglycerol catabolism by Carboxylesterase 1 promotes aggressive colorectal carcinoma., Journal of Clinical Investigation, ISSN: 0021-9738
The ability to adapt to low-nutrient microenvironments is essential for tumor-cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription-factor pathway associates with advanced disease stages and shorter survival in CRC patients. NF-κB has been shown to drive tumor-promoting inflammation, cancer-cell survival and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-κB affects the metabolic adaptations that fuel aggressive disease in CRC patients is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-κB-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC-cell survival via cell-autonomous mechanisms that fuel fatty-acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight CRC patients. Accordingly, NF-κB drove CES1 expression in CRC consensus molecular subtype (CMS)4, associated with obesity, stemness and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator, HNF4A, in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavourable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.
Manoli E, Mason S, Ford L, et al., 2021, Validation of ultrasonic harmonic scalpel for real-time tissue identification using rapid evaporative ionization mass spectrometry, Analytical Chemistry, Vol: 93, Pages: 5906-5916, ISSN: 0003-2700
In this study, we integrate rapid evaporative ionization mass spectrometry (REIMS) with the Harmonic scalpel, an advanced laparoscopic surgical instrument that utilizes ultrasound energy to dissect and coagulate tissues. It provides unparalleled manipulation capability to surgeons and has superseded traditional electrosurgical tools particularly in abdominal surgery, but is yet to be validated with REIMS. The REIMS platform coupled with the Harmonic device was shown to produce tissue-specific lipid profiles through the analysis of porcine tissues in both negative and positive ionization modes. Comparison with other methods of electrosurgical dissection, such as monopolar electrosurgery and CO2 laser, showed spectral differences in the profile dependent on the energy device used. The Harmonic device demonstrated major spectral differences in the phospholipid region of m/z 600–1000 compared with the monopolar electrosurgical and CO2 laser-generated spectra. Within the Harmonic REIMS spectra, high intensities of diglycerides and triglycerides were observed. In contrast, monopolar electrosurgical and laser spectra demonstrated high abundances of glycerophospholipids. The Harmonic scalpel was able to differentiate between the liver, muscle, colon, and small intestine, demonstrating 100% diagnostic accuracy. The validation of the Harmonic device–mass spectrometry combination will allow the platform to be used safely and robustly for real-time in vivo surgical tissue identification in a variety of clinical applications.
Antonowicz S, Bodai Z, Wiggins T, et al., 2021, Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma, Nature Communications, Vol: 12, ISSN: 2041-1723
Volatile aldehydes are enriched in esophageal adenocarcinoma (EAC) patients’ breath and could improve early diagnosis, however the mechanisms of their production are unknown. Here, we show that weak aldehyde detoxification characterizes EAC, which is sufficient to cause endogenous aldehyde accumulation in vitro. Two aldehyde groups are significantly enriched in EAC biopsies and adjacent tissue: (i) short-chain alkanals, and (ii) medium-chain alkanals, including decanal. The short-chain alkanals form DNA-adducts, which demonstrates genotoxicity and confirms inadequate detoxification. Metformin, a putative aldehyde scavenger, reduces this toxicity. Tissue and breath concentrations of the medium-chain alkanal decanal are correlated, and increased decanal is linked to reduced ALDH3A2 expression, TP53 deletion, and adverse clinical features. Thus, we present a model for increased exhaled aldehydes based on endogenous accumulation from reduced detoxification, which also causes therapeutically actionable genotoxicity. These results support EAC early diagnosis trials using exhaled aldehyde analysis.
Race AM, Sutton D, Hamm G, et al., 2021, Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration, ANALYTICAL CHEMISTRY, Vol: 93, Pages: 3061-3071, ISSN: 0003-2700
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- Citations: 23
Dannhorn A, Ling S, Powell S, et al., 2021, Evaluation of UV-C Decontamination of Clinical Tissue Sections for Spatially Resolved Analysis by Mass Spectrometry Imaging (MSI), ANALYTICAL CHEMISTRY, Vol: 93, Pages: 2767-2775, ISSN: 0003-2700
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- Citations: 4
Sands CJ, Gómez-Romero M, Correia G, et al., 2021, Representing the metabolome with high fidelity: range and response as quality control factors in LC-MS-based global profiling., Analytical Chemistry, Vol: 93, Pages: 1924-1933, ISSN: 0003-2700
Liquid chromatography-mass spectrometry (LC-MS) is a powerful and widely used technique for measuring the abundance of chemical species in living systems. Its sensitivity, analytical specificity, and direct applicability to biofluids and tissue extracts impart great promise for the discovery and mechanistic characterization of biomarker panels for disease detection, health monitoring, patient stratification, and treatment personalization. Global metabolic profiling applications yield complex data sets consisting of multiple feature measurements for each chemical species observed. While this multiplicity can be useful in deriving enhanced analytical specificity and chemical identities from LC-MS data, data set inflation and quantitative imprecision among related features is problematic for statistical analyses and interpretation. This Perspective provides a critical evaluation of global profiling data fidelity with respect to measurement linearity and the quantitative response variation observed among components of the spectra. These elements of data quality are widely overlooked in untargeted metabolomics yet essential for the generation of data that accurately reflect the metabolome. Advanced feature filtering informed by linear range estimation and analyte response factor assessment is advocated as an attainable means of controlling LC-MS data quality in global profiling studies and exemplified herein at both the feature and data set level.
Murta T, Steven RT, Nikula CJ, et al., 2021, Implications of Peak Selection in the Interpretation of Unsupervised Mass Spectrometry Imaging Data Analyses, ANALYTICAL CHEMISTRY, Vol: 93, Pages: 2309-2316, ISSN: 0003-2700
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- Citations: 14
Najumudeen AK, Ceteci F, Fey SK, et al., 2021, The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer, NATURE GENETICS, Vol: 53, ISSN: 1061-4036
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- Citations: 82
Jiwa N, Gandhewar R, Chauhan H, et al., 2020, Diagnostic accuracy of nipple aspirate fluid cytology in asymptomatic patients: a meta-analysis and systematic review of the literature, Annals of Surgical Oncology, Vol: 28, Pages: 3751-3760, ISSN: 1068-9265
PURPOSE: To calculate the diagnostic accuracy of nipple aspirate fluid (NAF) cytology. BACKGROUND: Evaluation of NAF cytology in asymptomatic patients conceptually offers a non-invasive method for either screening for breast cancer or else predicting or stratifying future cancer risk. METHODS: Studies were identified by performing electronic searches up to August 2019. A meta-analysis was conducted to attain an overall pooled sensitivity and specificity of NAF for breast cancer detection. RESULTS: A search through 938 studies yielded a total of 19 studies. Overall, 9308 patients were examined, with cytology results from 10,147 breasts [age (years), mean ± SD = 49.73 ± 4.09 years]. Diagnostic accuracy meta-analysis of NAF revealed a pooled specificity of 0.97 (95% CI 0.97-0.98), and sensitivity of 0.64 (95% CI 0.62-0.66). CONCLUSIONS: The diagnostic accuracy of nipple smear cytology is limited by poor sensitivity. If nipple fluid assessment is to be used for diagnosis, then emerging technologies for fluid biomarker analysis must supersede the current diagnostic accuracy of NAF cytology.
Kazanc E, Karali E, Wu V, et al., 2020, A multimodal analysis in breast cancer: Revealing metabolic heterogeneity using DESI-MS imaging with Laser-microdissection coupled transcriptome approach., AACR Virtual Special Conference on Tumor Heterogeneity - From Single Cells to Clinical Impact, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Shenker NS, Perdones-Montero A, Burke A, et al., 2020, Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months, NUTRIENTS, Vol: 12
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- Citations: 7
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