Search

Your search keyword '"Reinke, Stacey"' showing total 179 results
Start Over Author "Reinke, Stacey"
179 results on '"Reinke, Stacey"'

1. Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma

Author

Mendez, Kevin M., Begum, Sofina, Tiwari, Anshul, Sharma, Rinku, Chen, Qingwen, Kelly, Rachel S., Prince, Nicole, Huang, Mengna, Kachroo, Priyadarshini, Chu, Su H., Chen, Yulu, Lee-Sarwar, Kathleen, Broadhurst, David I., Reinke, Stacey N., Gerszten, Robert, Clish, Clary, Avila, Lydiana, Celedón, Juan C., Wheelock, Craig E., Weiss, Scott T., McGeachie, Michael, and Lasky-Su, Jessica A.

Published
2024
Full Text
View/download PDF

4. Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.

Author

Naz, Shama, Kolmert, Johan, Yang, Mingxing, Reinke, Stacey N, Kamleh, Muhammad Anas, Snowden, Stuart, Heyder, Tina, Levänen, Bettina, Erle, David J, Sköld, C Magnus, Wheelock, Åsa M, and Wheelock, Craig E

Subjects
Humans, Pulmonary Disease, Chronic Obstructive, Phosphoric Diester Hydrolases, MicroRNAs, Respiratory Function Tests, Chromatography, Liquid, Cross-Sectional Studies, Smoking, Sex Factors, Oxidative Stress, Middle Aged, Sweden, Female, Male, Statistics as Topic, Metabolomics, Pulmonary Disease, Chronic Obstructive, Chromatography, Liquid, Respiratory System, Medical and Health Sciences
Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I-II/A-B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography-high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10-7). Sex stratification indicated that the separation was driven by females (p=2.4×10-7) relative to males (p=4.0×10-4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10-3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p

Published
2017

5. Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant

Author

Afd Pharmacology, Pharmacology, Jones, Jacquelyn M., Reinke, Stacey N., Mousavi-Derazmahalleh, Mahsa, Garssen, Johan, Jenmalm, Maria C., Srinivasjois, Ravisha, Silva, Desiree, Keelan, Jeffrey, Prescott, Susan L., Palmer, Debra J., Christophersen, Claus T., Afd Pharmacology, Pharmacology, Jones, Jacquelyn M., Reinke, Stacey N., Mousavi-Derazmahalleh, Mahsa, Garssen, Johan, Jenmalm, Maria C., Srinivasjois, Ravisha, Silva, Desiree, Keelan, Jeffrey, Prescott, Susan L., Palmer, Debra J., and Christophersen, Claus T.

Published
2024

6. Introducing Undergraduate Students to Metabolomics Using Liquid Chromatography-High Resolution Mass Spectrometry Analysis of Horse Blood

Author

Boyce, Mary C., Lawler, Nathan G., Tu, Yingqi, and Reinke, Stacey N.

Abstract

Metabolomics is the data-driven science of small molecules. Untargeted metabolomics, using liquid chromatography-high resolution mass spectrometry (LC-HRMS), differs greatly from targeted metabolite assays, using nominal mass LC-MS instruments, as it generates thousands of metabolite features which are not quantified and are identified "post hoc." Thus, a substantial amount of time is dedicated to the data processing workflow. Despite the prevalence of untargeted metabolomics and LC-HRMS in contemporary research, undergraduate education in this area is almost nonexistent. To expose upper-division undergraduate analytical chemistry students to untargeted metabolomics, a realistic laboratory experiment, typical of biomedical research, was developed. In the clinic, hemolysis can result from poor sample handling. In this experiment, students artificially induced hemolysis in horse blood and assessed the resulting metabolomic differences. Using XCMS Online, an open-source online platform, and a guided worksheet, students navigated their processed data, learning how untargeted metabolomics differs from the targeted assays they previously performed. This experiment guided their understanding of key concepts such as the number of metabolite features detected, quality assessment, metabolite identification, and data visualization.

Published
2019
Full Text
View/download PDF

8. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K.F., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Praticò, G., Rao, M. Puig N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, A., Bedding, A., Behndig, A.F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, Grazyna, Braun, Armin, Campagna, D., Carayannopoulos, Leon, Casaulta, C., Chaleckis, Romanas, Dahlén, B., Davison, imothy, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Delin, Ingrid, Dennison, P., Dijkhuis, Annemiek, Dodson, Paul, Draper, Aleksandra, Dyson, K., Edwards, Jessica, El Hadjam, L., Emma, Rosalia, Ericsson, Magnus, Faulenbach, C., Flood, Breda, Galffy, G., Gallart, Hector, Garissi, D., Gent, J., Gerhardsson de Verdier, M., Gibeon, D., Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Guillmant-Farry, E., Henriksson, E., Hewitt, Lorraine, Hoda, U., Hu, Richard, Hu, Sile, Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Kerry, G., Klüglich, M., Knobel, Hugo, Kolmert, Johan, Konradsen, J.R., Kots, Maxim, Kretsos, Kosmas, Krueger, L., Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lantz, A.-S., Larminie, Christopher, Larsson, L.X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, Saeeda, Lowe, L.A., Manta, Alexander, Marouzet, Lisa, Martin, Jane, Mathon, Caroline, McEvoy, L., Meah, Sally, Menzies-Gow, A., Metcalf, Leanne, Mikus, Maria, Monk, Philip, Naz, Shama, Nething, K., Nicholas, Ben, Nihlén, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Pacino, Antonio, Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Pison, C., Postle, Anthony, Rahman-Amin, Malayka, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Riemann, K., Robberechts, Martine, Rocha, J.P., Rossios, C., Russell, Kirsty, Rutgers, Michael, Santini, G., Santoninco, Marco, Saqi, M., Schoelch, Corinna, Schofield, James P.R., Scott, S., Sehgal, N., Sjödin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Söderman, P., Sogbessan, A., Spycher, F., Staykova, Doroteya, Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thörngren, John-Olof, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C.M., Van Eyll, Jonathan, Versnel, Jenny, Vink, Anton, von Garnier, C., Vyas, A., Wald, Frans, Walker, Samantha, Ward, Jonathan, Wetzel, Kristiane, Wiegman, Coen, Williams, Siân, Yang, Xian, Yeyasingham, Elizabeth, Amgen, W. Yu, Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Östling, Jörgen, van Geest, Marleen, Jevnikar, Zala, Wilson, Susan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanović, Ratko, and Vaarala, Outi

Published
2019
Full Text
View/download PDF

15. Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Author

Read, James F., primary, Serralha, Michael, additional, Mok, Danny, additional, Holt, Barbara J., additional, Cruickshank, Mark, additional, Karpievitch, Yuliya V., additional, Broadhurst, David I., additional, Sly, Peter D., additional, Strickland, Deborah H., additional, Reinke, Stacey N., additional, Holt, Patrick G., additional, and Bosco, Anthony, additional

Published
2022
Full Text
View/download PDF

18. Changes to the gut microbiome in young children showing early behavioral signs of autism

Author

Jones, Jacquelyn, Reinke, Stacey N., Mousavi-Derazmahalleh, Mahsa, Palmer, Debra J., Christophersen, Claus T., Jones, Jacquelyn, Reinke, Stacey N., Mousavi-Derazmahalleh, Mahsa, Palmer, Debra J., and Christophersen, Claus T.

Abstract

The human gut microbiome has increasingly been associated with autism spectrum disorder (ASD), which is a neurological developmental disorder, characterized by impairments to social interaction. The ability of the gut microbiota to signal across the gut-brain-microbiota axis with metabolites, including short-chain fatty acids, impacts brain health and has been identified to play a role in the gastrointestinal and developmental symptoms affecting autistic children. The fecal microbiome of older children with ASD has repeatedly shown particular shifts in the bacterial and fungal microbial community, which are significantly different from age-matched neurotypical controls, but it is still unclear whether these characteristic shifts are detectable before diagnosis. Early microbial colonization patterns can have long-lasting effects on human health, and pre-emptive intervention may be an important mediator to more severe autism. In this study, we characterized both the microbiome and short-chain fatty acid concentrations of fecal samples from young children between 21 and 40 months who were showing early behavioral signs of ASD. The fungal richness and acetic acid concentrations were observed to be higher with increasing autism severity, and the abundance of several bacterial taxa also changed due to the severity of ASD. Bacterial diversity and SCFA concentrations were also associated with stool form, and some bacterial families were found with differential abundance according to stool firmness. An exploratory analysis of the microbiome associated with pre-emptive treatment also showed significant differences at multiple taxonomic levels. These differences may impact the microbial signaling across the gut-brain-microbiota axis and the neurological development of the children.

Published
2022

19. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

INTRODUCTION: Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. METHODS: Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. RESULTS: A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10-20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10-4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. CONCLUSIONS: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carn

Published
2022
Full Text
View/download PDF

20. Metabolomics in pulmonary medicine: Extracting the most from your data

Author

Reinke, Stacey N., Chaleckis, Romanas, Wheelock, Craig E., Reinke, Stacey N., Chaleckis, Romanas, and Wheelock, Craig E.

Abstract

The metabolome enables unprecedented insight into biochemistry, providing an integrated signature of the genome, transcriptome, proteome and exposome. Measurement requires rigorous protocols combined with specialised data analysis to achieve its promise.

Published
2022

21. Metabolomics reveals mouse plasma metabolite responses to acute exercise and effects of disrupting AMPK-glycogen interactions

Author

Belhaj, Mehdi R., Lawler, Nathan G., Hawley, John A., Broadhurst, David I., Hoffman, Nolan J., Reinke, Stacey N., Belhaj, Mehdi R., Lawler, Nathan G., Hawley, John A., Broadhurst, David I., Hoffman, Nolan J., and Reinke, Stacey N.

Abstract

Introduction: The AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that becomes activated by exercise and binds glycogen, an important energy store required to meet exercise-induced energy demands. Disruption of AMPK-glycogen interactions in mice reduces exercise capacity and impairs whole-body metabolism. However, the mechanisms underlying these phenotypic effects at rest and following exercise are unknown. Furthermore, the plasma metabolite responses to an acute exercise challenge in mice remain largely uncharacterized. Methods : Plasma samples were collected from wild type (WT) and AMPK double knock-in (DKI) mice with disrupted AMPK-glycogen binding at rest and following 30-min submaximal treadmill running. An untargeted metabolomics approach was utilized to determine the breadth of plasma metabolite changes occurring in response to acute exercise and the effects of disrupting AMPK-glycogen binding. Results: Relative to WT mice, DKI mice had reduced maximal running speed (p < 0.0001) concomitant with increased body mass (p < 0.01) and adiposity (p < 0.001). A total of 83 plasma metabolites were identified/annotated, with 17 metabolites significantly different (p < 0.05; FDR < 0.1) in exercised (↑ 6; ↓ 11) versus rested mice, including amino acids, acylcarnitines and steroid hormones. Pantothenic acid was reduced in DKI mice versus WT. Distinct plasma metabolite profiles were observed between the rest and exercise conditions and between WT and DKI mice at rest, while metabolite profiles of both genotypes converged following exercise. These differences in metabolite profiles were primarily explained by exercise-associated increases in acylcarnitines and steroid hormones as well as decreases in amino acids and derivatives following exercise. DKI plasma showed greater decreases in amino acids following exercise versus WT. Conclusion : This is the first study to map mouse plasma metabolomic changes following a bout of acute exercise in W

Published
2022

22. Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Author

Read, James F., Serralha, Michael, Mok, Danny, Holt, Barbara J., Cruickshank, Mark, Karpievitch, Yuliya V., Broadhurst, David I., Sly, Peter D., Strickland, Deborah H., Reinke, Stacey N., Holt, Patrick G., Bosco, Anthony, Read, James F., Serralha, Michael, Mok, Danny, Holt, Barbara J., Cruickshank, Mark, Karpievitch, Yuliya V., Broadhurst, David I., Sly, Peter D., Strickland, Deborah H., Reinke, Stacey N., Holt, Patrick G., and Bosco, Anthony

Abstract

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n = 50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC = 0.724). Connectivity patterns within this network were stronger among susceptible individuals, and a systems biology approach identified IRF1 as a putative master regulator of this response. These findings were specific to the LPS-induced interferon response and were not observed following activation of viral nucleic acid sensing pathways. Comparison of responses at birth versus age 5 demonstrated that LPS-induced interferon responses but not responses triggered by viral nucleic acid sensing pathways may be subject to strong developmental regulation. These data suggest that the risk of sLRI in early life is in part already determined at birth, and additionally that the developmental status of LPS-induced interferon responses may be a key determinant of susceptibility. Our findings provide a rationale for the identification of at-risk infants for early intervention aimed at sLRI prevention and identifies targets which may be relevant for drug development.

Published
2022

23. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6x10(-20)), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5x10(-4)), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carniti

Published
2022

25. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., primary, Naz, Shama, additional, Chaleckis, Romanas, additional, Gallart-Ayala, Hector, additional, Kolmert, Johan, additional, Kermani, Nazanin Z., additional, Tiotiu, Angelica, additional, Broadhurst, David I., additional, Lundqvist, Anders, additional, Olsson, Henric, additional, Ström, Marika, additional, Wheelock, Åsa M., additional, Gómez, Cristina, additional, Ericsson, Magnus, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Scholfield, James, additional, Loza, Matthew, additional, Baribaud, Frédéric, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Behndig, Annelie, additional, Singer, Florian, additional, Musial, Jacek, additional, Shaw, Dominick E., additional, Dahlén, Barbro, additional, Hu, Sile, additional, Lasky-Su, Jessica, additional, Sterk, Peter J., additional, Chung, Kian Fan, additional, Djukanovic, Ratko, additional, Dahlén, Sven-Erik, additional, Adcock, Ian M., additional, and Wheelock, Craig E., additional

Published
2021
Full Text
View/download PDF

26. The carnitine pathway is dysregulated in asthma in an oral corticosteroid-independent mechanism

Author

Reinke, Stacey, primary, Naz, Shama, additional, Kermani, Nazanin, additional, Chaleckis, Romanas, additional, Kolmert, Johan, additional, Ström, Marika, additional, Wheelock, Åsa, additional, Djukanovic, Ratko, additional, Chung, Fan, additional, Adcock, Ian, additional, Dahlen, Sven-Erik, additional, Wheelock, Craig, additional, and Ubiopred Study Group, ., additional

Published
2021
Full Text
View/download PDF

27. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

Introduction: Asthma is a heterogeneous disease with poorly defined phenotypes. Severe asthmatics often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods: Baseline urine was collected prospectively from healthy participants (n=100), mild-to-moderate asthmatics (n=87) and severe asthmatics (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from severe asthmatics (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results: Ninety metabolites were identified, with 40 significantly altered (p<0.05, FDR<0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and mild-to-moderate asthmatics differed significantly from severe asthmatics (p=2.6×10−20), OCS-treated asthmatics differed significantly from non-treated (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the necessity to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighti

Published
2021

33. Stratification of asthma phenotypes by airway proteomic signatures

Author

Schofield, James P. R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Batuwitage, M. K., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J. M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klueglich, M., Knowles, R., Konradsen, J. R., Kretsos, K., Krueger, L., Lantz, A. -S, Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L. A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C. S., Nething, K., Nihlen, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Pratico, G., Puig Valls, M., Riemann, K., Rocha, J. P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Soderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W. M., van Drunen, C. M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Adriaens, Nora, Aliprantis, Antonios, Alving, Kjell, Bakke, Per, Balgoma, David, Barber, Clair, Baribaud, Frederic, Bates, Stewart, Bautmans, An, Beleta, Jorge, Bochenek, Grazyna, Braun, Armin, Carayannopoulos, Leon, Rocha, Joao Pedro Carvalho da Purificacao, Chaleckis, Romanas, D'Amico, Arnaldo, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Dijkhuis, Annemiek, Draper, Aleksandra, Edwards, Jessica, Emma, Rosalia, Ericsson, Magnus, Flood, Breda, Gallart, Hector, Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Haughney, John, Hewitt, Lorraine, Hohlfeld, Jens, Holweg, Cecile, Hu, Richard, Hu, Sile, Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Knobel, Hugo, Kolmert, Johan, Kots, Maxim, Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lone-Latif, Saeeda, Loza, Matthew J., Marouzet, Lisa, Martin, Jane, Masefield, Sarah, Mathon, Caroline, Meah, Sally, Meiser, Andrea, Metcalf, Leanne, Mikus, Maria, Miralpeix, Montse, Monk, Philip, Naz, Shama, Nilsson, Peter, Ostling, Jorgen, Pacino, Antonio, Palkonen, Susanna, Pavlidis, Stelios, Pennazza, Giorgio, Petren, Anne, Pink, Sandy, Postle, Anthony, Powell, Pippa, Rahman-Amin, Malayka, Rao, Navin, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Robberechts, Martine, Roberts, Amanda, Russell, Kirsty, Rutgers, Michael, Santoninco, Marco, Schoelch, Corinna, Sjodin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Thorngren, John-Olof, Thornton, Bob, Thorsen, Jonathan, van de Pol, Marianne, van Geest, Marleen, Versnel, Jenny, Vink, Anton, Wald, Frans, Walker, Samantha, Weiszhart, Zsoka, Wetzel, Kristiane, Wheelock, Craig E., Wiegman, Coen, Williams, Sian, Wilson, Susan J., Woodcock, Ashley, Yang, Xian, Yeyasingham, Elizabeth, Prins, Jan-Bas, Gahlemann, Martina, Visintin, Luigi, Evans, Hazel, Puhl, Martine, Buzermaniene, Lina, Hudson, Val, Bond, Laura, de Boer, Pim, Widdershoven, Guy, Sigmund, Ralf, Supple, David, Hamerlijnck, Dominique, Negus, Jenny, Kamphuis, Julitte, Sergison, Lehanne, Onstein, Susanne, MacNee, William, Bernardini, Renato, Bont, Louis, Wecksell, Per-Ake, Graduate School, AII - Inflammatory diseases, Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, Publica, and Commission of the European Communities

Subjects
0301 basic medicine, Male, Proteomics, Allergy, Proteome, Neutrophils, Respiratory Medicine and Allergy, Transcriptome, 0302 clinical medicine, neutrophils, Forced Expiratory Volume, Immunology and Allergy, CD44, 610 Medicine & health, Lungmedicin och allergi, phenotypes, Middle Aged, medicine.anatomical_structure, Phenotype, 1107 Immunology, Female, eosinophils, medicine.symptom, Life Sciences & Biomedicine, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, Computational biology, 03 medical and health sciences, Young Adult, proteomics, Eosinophilia, medicine, Humans, U-BIOPRED Study Group, Asthma, Aged, Science & Technology, Microarray analysis techniques, business.industry, Sputum, biomarkers, DEGRADATION, Eosinophil, medicine.disease, Eosinophils, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, business
Abstract

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies. asthma proteomics biomarkers eosinophils neutrophils

Published
2019

34. Multi-omics analysis of immune-metabolic blood responses of very preterm infants for improving diagnosis of late-onset sepsis

Author

Currie, Andrew, Strunk, Tobias, Maker, Garth, Reinke, Stacey, Decuypere, S., Ng, Sherrianne Qin Yin, Currie, Andrew, Strunk, Tobias, Maker, Garth, Reinke, Stacey, Decuypere, S., and Ng, Sherrianne Qin Yin

Abstract

Very preterm infants are at highest risk of developing late-onset sepsis (LOS) through nosocomial infection, but our understanding of the associated transcriptional and metabolic responses remains very limited. Interrogating the neonatal immunometabolome could provide novel insights into the complex and dynamic pathophysiology and has potential to identify new signatures/biomarkers and improve LOS diagnosis. We hypothesised that neonatal sepsis will trigger characteristic changes in transcriptional regulation of critical innate immune response genes that will relate to their blood metabolome. Additionally, that the pathophysiological changes can be used to identify infected infants using a minimum metabolic and transcriptional signature specific for LOS. The blood transcriptome and plasma metabolome of very preterm infants with suspected LOS were profiled using RNA sequencing (RNA-seq) (n=18) and non-targeted liquid chromatography-mass spectrometry (LC-MS; n=20). Transcriptional profiling included bioinformatic and statistical analyses consisting of differential gene expression analysis, over-representation analysis, and protein-protein interaction (PPI) network and pathway enrichment analysis. Metabolomic analyses consisted of univariate and multivariate statistical methods including principal component analysis (PCA), partial least squaresdiscriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The metabolite features potentially important for discriminating infants with confirmed LOS, possible LOS and without LOS were identified using stringent criteria of: p<0.05, fold-change (FC)>3 and OPLS-DA variable importance in projection (VIP)>1. Separately, we used a multi-dimensional approach by integrating the transcriptomic, metabolomic, demographic and laboratory data of matching very preterm infants with suspected LOS using multiple factor analysis (MFA; n=17) to assess patient classification. Our transcriptomic findings s

Published
2019

35. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, primary, van Geest, Marleen, additional, Schofield, James P.R., additional, Jevnikar, Zala, additional, Wilson, Susan, additional, Ward, Jonathan, additional, Lutter, Rene, additional, Shaw, Dominick E., additional, Bakke, Per S., additional, Caruso, Massimo, additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandström, Thomas, additional, Sun, Kai, additional, Pandis, Ioannis, additional, Auffray, Charles, additional, Sousa, Ana R., additional, Guo, Yike, additional, Adcock, Ian M., additional, Howarth, Peter, additional, Chung, Kian Fan, additional, Bigler, Jeanette, additional, Sterk, Peter J., additional, Skipp, Paul J., additional, Djukanović, Ratko, additional, Vaarala, Outi, additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, K.F., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Powell, P., additional, Praticò, G., additional, Rao, M. Puig N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, Wilson, S.J., additional, Aliprantis, Antonios, additional, Allen, David, additional, Alving, Kjell, additional, Badorrek, P., additional, Balgoma, David, additional, Ballereau, S., additional, Barber, Clair, additional, Batuwitage, Manohara Kanangana, additional, Bautmans, A., additional, Bedding, A., additional, Behndig, A.F., additional, Beleta, Jorge, additional, Berglind, A., additional, Berton, A., additional, Bochenek, Grazyna, additional, Braun, Armin, additional, Campagna, D., additional, Carayannopoulos, Leon, additional, Casaulta, C., additional, Chaleckis, Romanas, additional, Dahlén, B., additional, Davison, imothy, additional, De Alba, Jorge, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, P., additional, Dijkhuis, Annemiek, additional, Dodson, Paul, additional, Draper, Aleksandra, additional, Dyson, K., additional, Edwards, Jessica, additional, El Hadjam, L., additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Faulenbach, C., additional, Flood, Breda, additional, Galffy, G., additional, Gallart, Hector, additional, Garissi, D., additional, Gent, J., additional, Gerhardsson de Verdier, M., additional, Gibeon, D., additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hewitt, Lorraine, additional, Hoda, U., additional, Hu, Richard, additional, Hu, Sile, additional, Hu, X., additional, Jeyasingham, E., additional, Johnson, K., additional, Jullian, N., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Kerry, G., additional, Klüglich, M., additional, Knobel, Hugo, additional, Kolmert, Johan, additional, Konradsen, J.R., additional, Kots, Maxim, additional, Kretsos, Kosmas, additional, Krueger, L., additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, A.-S., additional, Larminie, Christopher, additional, Larsson, L.X., additional, Latzin, P., additional, Lazarinis, N., additional, Lemonnier, N., additional, Lone-Latif, Saeeda, additional, Lowe, L.A., additional, Manta, Alexander, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Mathon, Caroline, additional, McEvoy, L., additional, Meah, Sally, additional, Menzies-Gow, A., additional, Metcalf, Leanne, additional, Mikus, Maria, additional, Monk, Philip, additional, Naz, Shama, additional, Nething, K., additional, Nicholas, Ben, additional, Nihlén, U., additional, Nilsson, Peter, additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pacino, Antonio, additional, Palkonen, Susanna, additional, Pellet, J., additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Pison, C., additional, Postle, Anthony, additional, Rahman-Amin, Malayka, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, K., additional, Robberechts, Martine, additional, Rocha, J.P., additional, Rossios, C., additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, G., additional, Santoninco, Marco, additional, Saqi, M., additional, Schoelch, Corinna, additional, Scott, S., additional, Sehgal, N., additional, Sjödin, Marcus, additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, P., additional, Sogbessan, A., additional, Spycher, F., additional, Staykova, Doroteya, additional, Stephan, S., additional, Stokholm, J., additional, Strandberg, K., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Thörngren, John-Olof, additional, Thorsen, Jonathan, additional, Valente, S., additional, van de Pol, Marianne, additional, van Drunen, C.M., additional, Van Eyll, Jonathan, additional, Versnel, Jenny, additional, Vink, Anton, additional, von Garnier, C., additional, Vyas, A., additional, Wald, Frans, additional, Walker, Samantha, additional, Wetzel, Kristiane, additional, Wiegman, Coen, additional, Williams, Siân, additional, Yang, Xian, additional, Yeyasingham, Elizabeth, additional, Amgen, W. Yu, additional, Zetterquist, W., additional, Zolkipli, Z., additional, and Zwinderman, A.H., additional

Published
2019
Full Text
View/download PDF

36. Alterations in measures of systemic inflammation among adults born preterm

Author

Gao, Jing, primary, Um-Bergström, Petra, additional, Pourbazargan, Melvin, additional, Berggren-Broström, Eva, additional, Merikallio, Heta, additional, Kaarteenaho, Riitta, additional, Reinke, Stacey, additional, Wheelock, Craig, additional, Melén, Erik, additional, Lindén, Anders, additional, Wheelock, Asa, additional, and Sköld, Magnus, additional

Published
2019
Full Text
View/download PDF

37. OnPLS-Based Multi-Block Data Integration : A Multivariate Approach to Interrogating Biological Interactions in Asthma

Author

Reinke, Stacey N., Galindo-Prieto, Beatriz, Skotare, Tomas, Broadhurst, David I., Singhania, Akul, Horowitz, Daniel, Djukanovic, Ratko, Hinks, Timothy S. C., Geladi, Paul, Trygg, Johan, Wheelock, Craig E., Reinke, Stacey N., Galindo-Prieto, Beatriz, Skotare, Tomas, Broadhurst, David I., Singhania, Akul, Horowitz, Daniel, Djukanovic, Ratko, Hinks, Timothy S. C., Geladi, Paul, Trygg, Johan, and Wheelock, Craig E.

Abstract

Integration of multiomics data remains a key challenge in fulfilling the potential of comprehensive systems biology. Multiple-block orthogonal projections to latent structures (OnPLS) is a Multi projection method that simultaneously models multiple data matrices, reducing feature space without relying on a priori biological knowledge. In order to improve the interpretability of OnPLS models, the associated multi-block variable influence on orthogonal projections (MB-VIOP) method is used to identify variables with the highest contribution to the model. This study combined OnPLS and MB-VIOP with interactive visualization methods to interrogate an exemplar multiomics study, using a subset of 22 individuals from an asthma cohort. Joint data structure in six data blocks was assessed: transcriptomics; metabolomics; targeted assays for sphingolipids, oxylipins, and fatty acids; and a clinical block including lung function, immune cell differentials, and cytokines. The model identified seven components, two of which had contributions from all blocks (globally joint structure) and five that had contributions from two to five blocks (locally joint structure). Components 1 and 2 were the most informative, identifying differences between healthy controls and asthmatics and a disease sex interaction, respectively. The interactions between features selected by MB-VIOP were visualized using chord plots, yielding putative novel insights into asthma disease pathogenesis, the effects of asthma treatment, and biological roles of uncharacterized genes. For example, the gene ATP6 V1G1, which has been implicated in osteoporosis, correlated with metabolites that are dysregulated by inhaled corticoid steroids (ICS), providing insight into the mechanisms underlying bone density loss in asthma patients taking ICS. These results show the potential for OnPLS, combined with MB-VIOP variable selection and interaction visualization techniques, to generate hypotheses from multiomics studies and in

Published
2018
Full Text
View/download PDF

38. OnPLS-Based Multi-Block Data Integration: A Multivariate Approach to Interrogating Biological Interactions in Asthma

Author

Reinke, Stacey N., primary, Galindo-Prieto, Beatriz, additional, Skotare, Tomas, additional, Broadhurst, David I., additional, Singhania, Akul, additional, Horowitz, Daniel, additional, Djukanović, Ratko, additional, Hinks, Timothy S.C., additional, Geladi, Paul, additional, Trygg, Johan, additional, and Wheelock, Craig E., additional

Published
2018
Full Text
View/download PDF

39. Late Breaking Abstract - Elevated airway lymphocytes in adults born prematurely with a history of bronchopulmonary dysplasia

Author

Gao, Jing, primary, Um-Bergstrom, Petra, additional, Pourbazargan, Melvin, additional, Berggren-Brostrom, Eva, additional, Merikallio, Heta, additional, Kaarteenaho, Riitta, additional, Reinke, Stacey, additional, Wheelock, Craig E, additional, Melen, Erik, additional, Linden, Anders, additional, Wheelock, Asa M, additional, and Skold, C Magnus, additional

Published
2018
Full Text
View/download PDF

40. Untargeted metabolomics of childhood asthma exacerbations from retrospectively collected serum samples

Author

Reinke, Stacey, Abbiss, Hayley, Laing, Ingrid, Trengrove, Robert, Mendez, Kevin Milton, Reinke, Stacey, Abbiss, Hayley, Laing, Ingrid, Trengrove, Robert, and Mendez, Kevin Milton

Abstract

Asthma is a common chronic inflammatory disease of the airways, affecting 360 million people globally. It is characterised by chronic inflammation, recurrent episodes of bronchoconstriction and mucosal hypersecretion. Symptoms include chest tightness, shortness of breath, coughing and wheezing. Oral corticosteroids used for the treatment of asthma have adverse effects, including bone mineralisation and adrenal suppression. Not all children with acute asthma-like symptoms will have persistent asthma in the future. This is particularly common at a pre-school age. This persistence is only known retrospectively. Identifying children early in their disease course can better direct treatment. Additionally, further understanding of the underlying disease mechanisms can direct novel therapies. Metabolomics is the systematic study of metabolites in a biological system. Metabolites are low molecular weight biochemical that are reactants, intermediates and end products of biological reactions. They are highly sensitive and are a snapshot of a particular biochemistry and/or pathophysiology. However, they are also highly sensitive to analytical variation. Thus, there were three aims in this study: to assess the impact of potentially limiting factors of retrospectively collected serum samples on metabolomic analysis; to determine whether metabolomics can identify potential biomarkers to distinguish wheeze/asthma exacerbation and control groups; and to determine whether metabolomics-derived biomarkers can identify differences between preschool-aged and school-aged phenotypes. Serum samples were curated from the Mechanisms of Acute Viral Respiratory Infections in Children (MAVRIC) study. This cohort study recruited children upon presentation to the emergency department at Princess Margaret Hospital with acute lower respiratory illnesses including wheeze/asthma. One–hundred and sixty-one samples were from children with acute wheeze/asthma, and 51 were from healthy controls. Samples

Published
2017

42. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

Author

Lefaudeux, Diane, primary, De Meulder, Bertrand, additional, Loza, Matthew J., additional, Peffer, Nancy, additional, Rowe, Anthony, additional, Baribaud, Frédéric, additional, Bansal, Aruna T., additional, Lutter, Rene, additional, Sousa, Ana R., additional, Corfield, Julie, additional, Pandis, Ioannis, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Dahlén, Sven-Erik, additional, Fleming, Louise J., additional, Fowler, Stephen J., additional, Horvath, Ildiko, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandstrom, Thomas, additional, Shaw, Dominic E., additional, Singer, Florian, additional, Sterk, Peter J., additional, Roberts, Graham, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Auffray, Charles, additional, Chung, Kian Fan, additional, Adriaens, Nora, additional, Ahmed, Hassan, additional, Aliprantis, Antonios, additional, Alving, Kjell, additional, Badorek, Philipp, additional, Balgoma, David, additional, Barber, Clair, additional, Bautmans, An, additional, Behndig, Annelie F., additional, Bel, Elisabeth, additional, Beleta, Jorge, additional, Berglind, Ann, additional, Berton, Alix, additional, Bigler, Jeanette, additional, Bisgaard, Hans, additional, Bochenek, Grazyna, additional, Boedigheimer, Michael J., additional, Bøonnelykke, Klaus, additional, Brandsma, Joost, additional, Braun, Armin, additional, Brinkman, Paul, additional, Burg, Dominic, additional, Campagna, Davide, additional, Carayannopoulos, Leon, additional, Carvalho da Purfição Rocha, João P., additional, Chaiboonchoe, Amphun, additional, Chaleckis, Romanas, additional, Coleman, Courtney, additional, Compton, Chris, additional, D'Amico, Arnaldo, additional, Dahlén, Barbro, additional, De Alba, Jorge, additional, de Boer, Pim, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, Patrick, additional, Dijkhuis, Annemiek, additional, Draper, Aleksandra, additional, Edwards, Jessica, additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Erpenbeck, Veit, additional, Erzen, Damijan, additional, Faulenbach, Cornelia, additional, Fichtner, Klaus, additional, Fitch, Neil, additional, Flood, Breda, additional, Frey, Urs, additional, Gahlemann, Martina, additional, Galffy, Gabriella, additional, Gallart, Hector, additional, Garret, Trevor, additional, Geiser, Thomas, additional, Gent, Jilaiha, additional, Gerhardsson de Verdier, Maria, additional, Gibeon, David, additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guo, Yi-Ke, additional, Hashimoto, Simone, additional, Haughney, John, additional, Hedlin, Gunilla, additional, Hekking, Pieter-Paul, additional, Henriksson, Elisabeth, additional, Hewitt, Lorraine, additional, Higgenbottam, Tim, additional, Hoda, Uruj, additional, Hohlfeld, Jans, additional, Holweg, Cecile, additional, Howarth, Peter, additional, Hu, Richard, additional, Hu, Sile, additional, Hu, Xugang, additional, Hudson, Val, additional, James, Anna J., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Klüglich, Matthias, additional, Knobel, Hugo, additional, Knowles, Richard, additional, Knox, Alan, additional, Kolmert, Johan, additional, Konradsen, Jon, additional, Kots, Maxim, additional, Krueger, Linn, additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, Ann-Sofie, additional, Larsson, Lars, additional, Lazarinis, Nikos, additional, Lone-Satif, Saeeda, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Masefield, Sarah, additional, Mathon, Caroline, additional, Matthews, John G., additional, Mazein, Alexander, additional, Meah, Sally, additional, Maiser, Andrea, additional, Menzies-Gow, Andrew, additional, Metcalf, Leanne, additional, Middelveld, Roelinde, additional, Mikus, Maria, additional, Miralpeix, Montse, additional, Monk, Philips, additional, Mores, Nadia, additional, Murray, Clare S., additional, Musial, Jacek, additional, Myles, David, additional, Naz, Shama, additional, Nething, Katja, additional, Nicholas, Ben, additional, Nihlen, Ulf, additional, Nilsson, Peter, additional, Nordlund, Björn, additional, Östling, Jörgen, additional, Pacino, Antonio, additional, Pahus, Laurie, additional, Palkonnen, Susanna, additional, Pavlidis, Stelios, additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Postle, Anthony, additional, Powel, Pippa, additional, Rahman-Amin, Malayka, additional, Rao, Navin, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, Kathrin, additional, Riley, John, additional, Robberechts, Martine, additional, Roberts, Amanda, additional, Rossios, Christos, additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, Giuseppe, additional, Sentoninco, Marco, additional, Schoelch, Corinna, additional, Schofield, James P.R., additional, Seibold, Wolfgang, additional, Sigmund, Ralf, additional, Sjödin, Marcus, additional, Skipp, Paul J., additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, Päivi, additional, Sogbesan, Adesimbo, additional, Staykova, Doroteya, additional, Strandberg, Karin, additional, Sun, Kai, additional, Supple, David, additional, Szentkereszty, Marton, additional, Tamasi, Lilla, additional, Tariq, Kamran, additional, Thörngren, John-Olof, additional, Thornton, Bob, additional, Thorsen, Jonathan, additional, Valente, Salvatore, additional, van Aalderenm, Wim, additional, van de Pol, Marianne, additional, van Drunen, Kees, additional, van Geest, Marleen, additional, Versnel, Jenny, additional, Vestbo, Jorgen, additional, Vink, Anton, additional, Vissing, Nadja, additional, von Garnier, Christophe, additional, Wagerner, Arianne, additional, Wagers, Scott, additional, Wald, Frans, additional, Walker, Samantha, additional, Ward, Jonathan, additional, Weiszhart, Zsoka, additional, Wetzel, Kristiane, additional, Wheelock, Craig E., additional, Wiegman, Coen, additional, Williams, Siân, additional, Wilson, Susan J., additional, Woosdcock, Ashley, additional, Yang, Xian, additional, Yeyashingham, Elizabeth, additional, Yu, Wen, additional, Zetterquist, Wilhelm, additional, and Zwinderman, Koos, additional

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results