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21 results on '"Murray, C. S."'

1. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, M. S., Kolmert, J., Andersson, L. I., Ostling, J., Knowles, R. G., Gomez, C., Ericsson, M., Thorngren, J. -O., Khoonsari, P. E., Dahlen, B., Kupczyk, M., de Meulder, B., Auffray, C., Bakke, P. S., Beghe, Bianca, Bel, E. H., Caruso, M., Chanez, P., Chawes, B., Fowler, S. J., Gaga, M., Geiser, T., Gjomarkaj, M., Horvath, I., Howarth, P. H., Johnston, S. L., Joos, G., Krug, N., Montuschi, P., Musial, J., Nizankowska-Mogilnicka, E., Olsson, H. K., Papi, A., Rabe, K. F., Sandstrom, T., Shaw, D. E., Siafakas, N. M., Uhlen, M., Riley, J. H., Bates, S., Middelveld, R. J. M., Wheelock, C. E., Chung, K. F., Adcock, I. M., Sterk, P. J., Djukanovic, R., Nilsson, P., Dahlen, S. -E., James, A., Ahmed, H., Balgoma, D., Bansal, A. T., Baribaud, F., Bigler, J., Billing, B., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Checa, T., Compton, C. H., Corfield, J., Cunoosamy, D., D'Amico, A., Emma, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Frey, U., Gahlemann, M., Goss, V., Guo, Y. -K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. -P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C. T. J., Knox, A. J., Konradsen, J., Lazarinis, N., Lefaudeux, D., Li, T., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Miralpeix, M., Mores, N., Murray, C. S., Myles, D., Naz, S., Nordlund, B., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Rao, N., Reinke, S., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Sjodin, M., Skipp, P. J., Sousa, A. R., Sun, K., Thornton, B., Uddin, M., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, A., Wilson, S. J., Yasinska, V., Brusselle, G. G., Campbell, D. A., Contoli, M., Damm, K., de Rudder, I., Delin, I., Devautour, C., Duplaga, M., Eduards, M., Ek, A., Ekstrom, T., Figiel, E., Gaber, F., Gauw, S., Gawlewicz-Mroczka, A., Gerding, D., Haque, S., Hewitt, L., Hiemstra, P. S., Holgate, S. T., Holloway, J., Kania, A., Kanniess, F., Karlsson, O., Kips, J. C., Kumlin, M., Lantz, A. -S., Magnussen, H., Mallia, P., Martling, I., Meziane, L., Oikonomidou, E., Olsson, M., Pace, E., Papadopouli, E., Papadopoulos, N., Plataki, M., Profita, M., Reinius, L. E., Richter, K., Robinson, D. S., Romagnoli, M., Samara, K., Schelfhout, V., Skedinger, M., Stamataki, E., ten Brinke, A., Vachier, I., Wallen-Nielsen, E., van Veen, I., Weersink, E., Zervas, E., and Ziolkowska-Graca, B.

Subjects
Blood Proteins, Humans, Inflammation, Proteomics, Severity of Illness Index, Steroids, Asthma, Quality of Life
Published
2022

3. 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., Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, 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., Djukanovi?, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., 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., 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., and Nething, K.

Abstract

© 2019 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.

Published
2019

4. Treatable traits in the European U-BIOPRED adult asthma cohorts

Author

Simpson, Andrew J., Hekking, Pieter-Paul, Shaw, Dominick E., Fleming, L. J., Roberts, Graham, Riley, John H., Bates, Stewart, Sousa, A. R., Bansal, A. T., Pandis, Ioannis, Sun, K., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Dahlen, Sven-Erik, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sandstrom, Thomas, Singer, Florian, Adcock, I. M., Wagers, Scott S., Djukanovic, R., Chung, Kian Fan, Sterk, P. J., Fowler, S. J., Ahmed, H., Auffray, C., Bakke, P., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., Dahlen, S. E., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., 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., Postle, A., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, T., Schofield, J. P. R., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., and Wilson, S. J.

Abstract

mprovements in asthma outcomes have stalled over the past decade, which may be attributed to treating patients on the basis of a generic diagnostic label. The taxonomy “Treatable Traits” was proposed by Agusti et al (2016) as a precision medicine approach for the diagnosis and management of chronic airway diseases that is based on the identification of genetic, phenotypic and psychosocial characteristics for which therapeutic interventions are known to improve respiratory health ...

Published
2019

7. 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, 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, and Wecksell, Per-Ake

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.

Published
2019
Full Text
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8. Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Author

Perotin, Jeanne-Marie, Schofield, James P. R., Wilson, Susan J., Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H., Sousa, Ana R., Dahlen, Sven-Erik, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Collins, Jane E., Davies, Donna E., Djukanovic, Ratko, Adcock, I. M., Ahmed, H., Auffray, C., Bakke, P., Banssal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, 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., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., 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., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, 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, An, Bedding, A., Behndig, A. F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, G., Braun, A., Campagna, D., Carayannopoulos, L., Casaulta, C., Chaleckis, Romanas, Dahlen, B., Davison, T., De Alba, J., De Lepeleire, I., Dekker, T., Delin, I., Dennison, P., Dijkhuis, A., Dodson, P., Dyson, K., Edwards, J., El Hadjam, L., Emma, R., Ericsson, M., Faulenbach, C., Flood, Breda, Galffy, G., Gallart, H., Garissi, D., Gent, J., de Verdier, M. Gerhardsson, Gibeon, D., Gomez, Cristina, Gove, K., Guillmant-Farry, E., Henriksson, E., Hewitt, L., Hoda, U., Hu, Richard, Hu, S., Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, J., Kennington, E. J., Kerry, D., Kerry, G., Klueglich, M., Knobel, H., Kolmert, Johan, Konradsen, J. R., Kots, M., Kretsos, Kosmas, Krueger, L., Kuo, S., Kupczyk, M., Lambrecht, B., Lantz, A-S, Larminie, Christopher, Larsson, L. X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, S., Lowe, L. A., Marouzet, L., Martin, J., Mathon, C., McEvoy, L., Meah, S., Menzies-Gow, A., Metcalf, L., Mikus, M., Monk, P., Naz, S., Nething, K., Nicholas, B., Nihlen, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Ostling, J., Pacino, A., Palkonen, S., Pellet, J., Pennazza, G., Petren, A., Pink, S., Pison, C., Postle, A., Rahman-Amin, M., Ravanetti, L., Ray, E., Reinke, S., Reynolds, L., Riemann, K., Robberechts, Martine, Rocha, J. P., Rossios, C., Russell, K., Rutgers, M., Santini, G., Santoninco, M., Saqi, M., Schoelch, C., Schofield, J. P. R., Scott, S., Sehgal, N., Sjodin, M., Smids, B., Smith, Caroline, Smith, J., Smith, K. M., Soderman, P., Sogbessan, A., Spycher, F., Staykova, D., Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thorngren, J-O, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C. M., Van Eyll, J., Versnel, J., Vink, A., von Garnier, C., Vyas, A., Wald, F., Walker, S., Ward, J., Wetzel, K., Wiegman, C., Williams, S., Yang, X., Yeyasingham, E., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Prins, J-B, Visintin, L., Evans, H., Puhl, M., Buzermaniene, L., Hudson, V., Bond, L., de Boer, P., Widdershoven, G., Supple, D., Hamerlijnck, D., Negus, J., Sergison, L., Onstein, S., MacNee, W., Bernardini, R., Bont, Louis, Wecksell, P-A, Draper, Aleksandra, Gozzard, Neil, Perotin, Jeanne-Marie, Schofield, James P. R., Wilson, Susan J., Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H., Sousa, Ana R., Dahlen, Sven-Erik, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Collins, Jane E., Davies, Donna E., Djukanovic, Ratko, Adcock, I. M., Ahmed, H., Auffray, C., Bakke, P., Banssal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, 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., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., 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., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, 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, An, Bedding, A., Behndig, A. F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, G., Braun, A., Campagna, D., Carayannopoulos, L., Casaulta, C., Chaleckis, Romanas, Dahlen, B., Davison, T., De Alba, J., De Lepeleire, I., Dekker, T., Delin, I., Dennison, P., Dijkhuis, A., Dodson, P., Dyson, K., Edwards, J., El Hadjam, L., Emma, R., Ericsson, M., Faulenbach, C., Flood, Breda, Galffy, G., Gallart, H., Garissi, D., Gent, J., de Verdier, M. Gerhardsson, Gibeon, D., Gomez, Cristina, Gove, K., Guillmant-Farry, E., Henriksson, E., Hewitt, L., Hoda, U., Hu, Richard, Hu, S., Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, J., Kennington, E. J., Kerry, D., Kerry, G., Klueglich, M., Knobel, H., Kolmert, Johan, Konradsen, J. R., Kots, M., Kretsos, Kosmas, Krueger, L., Kuo, S., Kupczyk, M., Lambrecht, B., Lantz, A-S, Larminie, Christopher, Larsson, L. X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, S., Lowe, L. A., Marouzet, L., Martin, J., Mathon, C., McEvoy, L., Meah, S., Menzies-Gow, A., Metcalf, L., Mikus, M., Monk, P., Naz, S., Nething, K., Nicholas, B., Nihlen, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Ostling, J., Pacino, A., Palkonen, S., Pellet, J., Pennazza, G., Petren, A., Pink, S., Pison, C., Postle, A., Rahman-Amin, M., Ravanetti, L., Ray, E., Reinke, S., Reynolds, L., Riemann, K., Robberechts, Martine, Rocha, J. P., Rossios, C., Russell, K., Rutgers, M., Santini, G., Santoninco, M., Saqi, M., Schoelch, C., Schofield, J. P. R., Scott, S., Sehgal, N., Sjodin, M., Smids, B., Smith, Caroline, Smith, J., Smith, K. M., Soderman, P., Sogbessan, A., Spycher, F., Staykova, D., Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thorngren, J-O, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C. M., Van Eyll, J., Versnel, J., Vink, A., von Garnier, C., Vyas, A., Wald, F., Walker, S., Ward, J., Wetzel, K., Wiegman, C., Williams, S., Yang, X., Yeyasingham, E., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Prins, J-B, Visintin, L., Evans, H., Puhl, M., Buzermaniene, L., Hudson, V., Bond, L., de Boer, P., Widdershoven, G., Supple, D., Hamerlijnck, D., Negus, J., Sergison, L., Onstein, S., MacNee, W., Bernardini, R., Bont, Louis, Wecksell, P-A, Draper, Aleksandra, and Gozzard, Neil

Published
2019
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9. IL-17-high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, 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., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, 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., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., 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., Pratico, G., Valls, M. Puig, Rao, 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., Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, 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., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, 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., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., 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., Pratico, G., Valls, M. Puig, Rao, 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., and Wilson, S. J.

Abstract

Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Published
2019
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12. A computational framework for complex disease stratification from multiple large-scale datasets

Author

De Meulder, B., Lefaudeux, D., Bansal, A. T., Mazein, A., Chaiboonchoe, A., Ahmed, H., Balaur, I., Saqi, M., Pellet, J., Ballereau, S., Lemonnier, N., Sun, K., Pandis, I., Yang, X., Batuwitage, M., Kretsos, K., van Eyll, J., Bedding, A., Davison, T., Dodson, P., Larminie, C., Postle, A., Corfield, J., Djukanovic, R., Chung, K. F., Adcock, I. M., Guo, Y. -K., Sterk, P. J., Manta, A., Rowe, A., Baribaud, F., Auffray, C., Gibeon, D., Hoda, U., Kuo, S., Meah, S., Meiser, A., Fleming, L. J., Hu, S., Pavlidis, S., Rossios, C., Russel, K., Wiegman, C., Nezhad, A. T., Oehmichen, A., O'Malley, D., Guitton, F., Emam, I., Agapow, P., Rice, P., Miles, S., Elyasigomari, V., Bel, E., Brinkman, P., Dekker, T., Dijkhuis, A., Hashimoto, S., Hekking, P. -P., Lone-Latif, S., Lutter, R., Ravanetti, L., Smids, B., van Aalderen, W., van de Pol, M., van Drunen, K., van Drunen, M., Wagener, A., Zwinderman, K., Adriaens, N., Carusi, A. M., Richard, F., Nogueira, M. M., Taibi, N., Brasier, O., Aliprantis, A., Alving, K., Faulenbach, C., Braun, A., Hohlfeld, J., Krug, N., Badorrek, P., Bakke, P., Berglind, A., Chaleckis, R., Dahlen, B., Delin, I., Gallart, H., Gomez, C., Hedlin, G., Henriksson, E., James, A. J., Kolmert, J., Konradsen, J., Kupczyk, M., Lantz, A. -S., Lazarinis, L., Mathon, C., Middelveld, R., Naz, S., Nordlund, B., Petren, A., Reinke, S., Sjodin, M., Soderman, P., Strandberg, K., Wheelock, C. E., Zetterquist, W., Balgoma, D., Brandsma, J., Burg, D., Dennison, P., Nicholas, B., Schofield, J. P. R., Skipp, P. J., Staykova, D., Tariq, K., Ward, J., Wilson, S. J., Barber, C., Loza, M. J., Bautmans, A., Sandstrom, T., Behndig, A. F., De Alba, J., Beleta, J., Berton, A., de Verdier, M. G., Nihlen, U., Ostling, J., Dalentoft, T., Lindgren, E., Boedigheimer, M. J., Hu, R., Hu, X., Yu, W., Bigler, J., Bonnelykke, K., Thorsen, J., Vising, N., Bisgaard, H., Bochenek, G., Caruso, M., Emma, R., Campagna, D., Thornton, B., Carayannopoulos, L., Gent, J., Manzies-Gow, A., Sogbesan, A., da Purificacao Rocha, P. C., Pedro, J., Chanez, P., Edwards, J., Flood, B., Hudson, V., Kennington, E. J., Metcalf, L., Rahman-Amin, M., Reynolds, L., Roberts, A., Smith, J., Supple, D., Versnel, J., Walker, S., Coleman, C., Hasan, S., Compton, C., Myles, D., Riley, J., Sousa, A. R., Yeyasingham, E., Pennazza, G., Santoninco, M., D'Amico, A., Dahlen, S. -E., de Boer, P., Robberechts, M., De Lepeleire, I., Fitch, N., Garret, T., Wagers, S., Draper, A., Thorngren, J. -O., Ericsson, M., Erpenbeck, V., Kluglich, M., Nething, K., Riemann, K., Schoelch, C., Seibold, W., Sigmund, R., Wald, F., Wetzel, K., Fichtner, K., Erzen, D., Galffy, G., Horvath, I., Szentkereszty, M., Tamasi, L., Fowler, S. J., Krueger, L., Singer, F., Frey, U., Gahlemann, M., Geiser, T., Hewitt, L., Howarth, P., Marouzet, L., Martin, J., Pink, S., Ray, E., Roberts, G., Smith, C., Gove, K., Gozzard, N., Williams, S., Haughney, J., Higgenbottam, T., Matthews, J. G., Holweg, C., Rutgers, M., Kamphuis, J., Kerry, D., Vink, A., Knobel, H., Knowles, R., Shaw, D. E., Smith, K. M., Know, A., Kots, M., Lambrecht, B., Masefield, S., Nilsson, P., Mikus, M., Miralpeix, M., Monk, P., Mores, N., Valente, S., Montuschi, P., Murray, C. S., Musial, J., Pacino, A., Pahus, L., Palkonen, S., Powel, P., Rao, N., Santini, G., Vestbo, J., von Garnier, C., Weiszhart, Z., Woodcock, A., Biryukov, M., Schneider, R., Herzinger, S., Satagopam, V., Gu, W., da Silva, A. B., Tielmann, A., Bergeron, J., Gaudette, A., Silberberg, A., Henderson, D., Hayat, S., Elefsinioti, A., Moltzen, E. K., Harbo, I. S., Birgitte, J., Bratfalean, D., Houston, P., Kisler, B., Capdevila, F. B., Verbeeck, D., Marchetti, G., Rahal, G., Schuermann, H. D., Mazuranok, L., Hendlich, M., Painell'S, L., Marren, D., Martasek, J., Rimell, J., Romacker, M., Braxenthaler, M., Sansone, S. -A., Rocca-Serra, P., Commission of the European Communities, Pulmonology, Graduate School, Experimental Immunology, Paediatric Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, ARD - Amsterdam Reproduction and Development, Consortium, U-Biopred Study Group And The Etriks, Rocca-Serra, P, Sansone, S, De Meulder, Bertrand [0000-0002-2108-7657], and Apollo - University of Cambridge Repository

Subjects
Quality Control, 0301 basic medicine, Computer science, Bioinformatics, Systems biology, Big data, Environmental data, Machine Learning, Set (abstract data type), 03 medical and health sciences, Structural Biology, Modelling and Simulation, Cluster Analysis, U-BIOPRED Study Group and the eTRIKS Consortium, Disease, False Positive Reactions, Cluster analysis, Molecular signatures, Molecular Biology, lcsh:QH301-705.5, ‘Omics data, 'Omics data, business.industry, Systems Biology, Applied Mathematics, 1199 Other Medical And Health Sciences, Data science, 3. Good health, Computer Science Applications, Systems medicine, 030104 developmental biology, lcsh:Biology (General), Feature (computer vision), Modeling and Simulation, Stratification, Scale (map), business, Biomarkers, Research Article
Abstract

Background Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-‘omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-‘omics signatures of disease states. Methods The framework is divided into four major steps: dataset subsetting, feature filtering, ‘omics-based clustering and biomarker identification. Results We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-‘omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. Conclusions This framework will help health researchers plan and perform multi-‘omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine. Electronic supplementary material The online version of this article (10.1186/s12918-018-0556-z) contains supplementary material, which is available to authorized users.

Published
2018
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13. Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers

Author

Brandsma, J., Goss, V., Yang, X., Bakke, P. S., Caruso, M., Chanez, P., Dahlen, S. -E., Fowler, S. J., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Shaw, D. E., Chung, K. F., Singer, F., Fleming, L. J., Sousa, A. R., Pandis, I., Bansal, A. T., Sterk, P. J., Djukanovic, R., Postle, A. D., Adcock, I. M., Ahmed, H., Auffray, C., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Howarth, P., James, A. J., Knowles, R. G., Knox, A. J., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pavlidis, S., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Skipp, 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., Pulmonology, AII - Inflammatory diseases, Commission of the European Communities, and Publica

Subjects
0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Epithelial lining fluid, Biochemistry, DISEASE, Analytical Chemistry, Cohort Studies, 0302 clinical medicine, Fibrosis, FIBROSIS, Induced sputum, Lung, COPD, Biochemistry and Molecular Biology, respiratory system, Middle Aged, Lipids, Healthy Volunteers, Cell biology, medicine.anatomical_structure, Phenotype, OBESITY, Original Article, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Life Sciences & Biomedicine, 0301 Analytical Chemistry, Bronchoalveolar Lavage Fluid, Sputum/chemistry, EXPRESSION, Adult, Settore BIO/14 - FARMACOLOGIA, DYNAMIC LIPIDOMICS, Adolescent, SPUTUM CELL COUNTS, BIOMARKERS, Biology, chronic obstructive pulmonary disease, Bronchoalveolar Lavage Fluid/chemistry, Endocrinology & Metabolism, 03 medical and health sciences, Young Adult, Lipids/analysis, Lung/cytology, Lipidomics, medicine, Humans, SURFACTANT LIPIDS, Aged, Science & Technology, pulmonary fibrosis, Mass spectrometry, Sputum, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences, Lipid metabolism, Pulmonary surfactant, medicine.disease, Molecular medicine, respiratory tract diseases, Weight status, 030104 developmental biology, 030228 respiratory system, ASTHMA, Biokemi och molekylärbiologi, Homeostasis
Abstract

Background Lung epithelial lining fluid (ELF)—sampled through sputum induction—is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort. Methods Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes. Results The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender. Conclusions We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism. Electronic supplementary material The online version of this article (10.1007/s11306-018-1412-2) contains supplementary material, which is available to authorized users.

Published
2018
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14. Finding protein-protein interaction patterns by contact map matching

Author

Melo, R. C., Ribeiro, C., Murray, C. S., Veloso, C. J. M., Carlos Silveira, Neshich, G., Meira Jr, W., Carceroni, R. L., Santoro, M. M., UFMG, GORAN NESHICH, CNPTIA, and UFMG.

Subjects
Mapas de contato, Bioinformatics, Bioinformática, Serine proteinases, Serine proteases, protein-protein interactions, Contact maps, Interação proteína-proteína
Abstract

We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

Published
2007

15. Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema : randomized controlled trial with follow-up until age 3 years

Author

Gore, C., Custovic, A., Tannock, G. W., Munro, K., Kerry, G., Johnson, K., Peterson, Christer, Morris, J., Chaloner, C., Murray, C. S., Woodcock, A., Gore, C., Custovic, A., Tannock, G. W., Munro, K., Kerry, G., Johnson, K., Peterson, Christer, Morris, J., Chaloner, C., Murray, C. S., and Woodcock, A.

Abstract

Background Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. Objective We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I3446 had a treatment effect or altered allergic disease progression. Methods Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen- sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD >= 10, consuming >= 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). Trial number: ISRCTN41490500. Results Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.416.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4-30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. Conclusion and Clinical Relevance We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an a

Published
2012
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16. Priority information needs in parents of children with asthma: results from a survey using a paired comparison approach.

Author

Kerry, G F, Caress, A L, Beaver, K, Custovic, A, Woodcock, A, Murray, C S, Kerry, G F, Caress, A L, Beaver, K, Custovic, A, Woodcock, A, and Murray, C S

Abstract

Background: Having appropriate information is important for parents of children with asthma, but evidence about the information parents would find most useful is lacking. Identifying the topics that are a priority for parents would help in tailoring asthma education. Methods: A survey was undertaken of parents of children with established asthma attending an outpatient clinic at a district general hospital in the Northwest of England. Data were collected using a structured asthma specific information needs questionnaire, which employed a Thurstonian paired comparisons approach. This consisted of all possible pairings of nine ‘‘core information needs’’, previously identified in adults with asthma (Caress, et al. Patient Educ Couns 2002;47:319–27), adapted for use with parents of children with asthma. Results: Parents of 29 children (child’s median age 8.0 years, IQ range 5.1–12.3; median time since asthma diagnosis 3.7 years) completed the survey. Information needs were prioritised as shown in the table (information needs with Thurstone scale values). Six (20%) respondents were satisfied/very satisfied with their level of information about their current top priority area, while six (20%) were dissatisfied/very dissatisfied. The majority of parents (25/29) were unable to identify additional information needs, while three parents highlighted the need for information on action to take when their child was unwell (that is, an asthma action plan). The majority of parents stated that they would most prefer to receive information from their child’s doctor (22/29) and/or asthma nurse (12/29). Main reasons for this choice were ‘‘confidence in their knowledge’’ and ‘‘familiarity with their child’s asthma’’. Conclusion: Further work is required to better understand why parents value specific items. Some parents identified the need for an asthma action plan. A larger study is now required to validate these findings, in particular to establish whether information about self-manag

Published
2005

20. Finding protein-protein interaction patterns by contact map matching.

Author

Melo RC, Ribeiro C, Murray CS, Veloso CJ, da Silveira CH, Neshich G, Meira W Jr, Carceroni RL, and Santoro MM

Subjects
Amino Acid Sequence, Animals, Aprotinin chemistry, Binding Sites, Cattle, Cluster Analysis, Databases, Protein, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Serine Endopeptidases chemistry, Protein Interaction Mapping methods
Abstract

We propose a novel method for defining patterns of contacts present in protein-protein complexes. A new use of the traditional contact maps (more frequently used for representation of the intra-chain contacts) is presented for analysis of inter-chain contacts. Using an algorithm based on image processing techniques, we can compare protein-protein interaction maps and also obtain a dissimilarity score between them. The same algorithm used to compare the maps can align the contacts of all the complexes and be helpful in the determination of a pattern of conserved interactions at the interfaces. We present an example for the application of this method by analyzing the pattern of interaction of bovine pancreatic trypsin inhibitors and trypsins, chymotrypsins, a thrombin, a matriptase, and a kallikrein - all classified as serine proteases. We found 20 contacts conserved in trypsins and chymotrypsins and 3 specific ones are present in all the serine protease complexes studied. The method was able to identify important contacts for the protein family studied and the results are in agreement with the literature.

Published
2007

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