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1. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Makela, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., Xu, C., dIRAS RA-2, Risk Assessment, Clinicum, Department of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J.M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D.S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B.N., Lodrup Carlsen, K.C., Koppelman, G.H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M.L., Maier, D., Melén, E., Palkonen, S., Smit, H.A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., Mceachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Subjects
multimorbidity, EUROPEAN INNOVATION PARTNERSHIP, humanos, Immunology, IGE SENSITIZATION, política de salud, Review, rhinitis, Inventions, Unión Europea, Hypersensitivity, Medicine and Health Sciences, Journal Article, Humans, Immunology and Allergy, ATOPIC-DERMATITIS, European Union, biología de sistemas, hipersensibilidad, inmunización, inmunoglobulina E, Asthma, Ige, Multimorbidity, Polysensitization, Rhinitis, BIRTH COHORT, IMMUNE-RESPONSES, Health Policy, Systems Biology, asthma, IgE, polysensitization, CHILDHOOD ASTHMA, invenciones, Immunoglobulin E, Prognosis, INTEGRATED CARE, pronóstico, rhiniti, CHRONIC RESPIRATORY-DISEASES, 3121 General medicine, internal medicine and other clinical medicine, Immunization, IMMUNOLOGICAL REACTIVITY, IMMUNOGLOBULIN-E
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016
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2. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Lodrup Carlsen, K. C., Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Makela, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, A., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Subjects
ddc:610
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

3. Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study

Author

Pinart, M, Albang, R, Maier, D, Duran-Tauleria, E, Mena, G, Gimeno-Santos, E, Sola, I, Garcia-Aymerich, J, Guerra, S, Stein, RT, Benet, M, Carlsen, KH, Herr, M, Jacquemin, B, Momas, I, Pin, I, Ranciere, F, Smit, HA, Varraso, R, Bonfill, X, Keil, T, Bousquet, J, and Anto, JM

Subjects
Phenotype, Urticaria, Allergy, Eczema, Disease definition, Anaphylaxis, Asthma, Rhinitis
Abstract

Background: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis. Methods: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers. Results: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%. Conclusions: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary. (C) 2015 S. Karger AG, Basel

Published
2015

4. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

5. Paving the way of systems biology and precision medicine in allergic diseases

Author

University of Helsinki, Clinicum, University of Helsinki, Departments of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., Xu, C., University of Helsinki, Clinicum, University of Helsinki, Departments of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

6. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

dIRAS RA-2, Risk Assessment, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, dIRAS RA-2, Risk Assessment, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Published
2016

7. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Published
2016

8. Paving the way of systems biology and precision medicine in allergic diseases: the Me DALL success story

Author

Bousquet, J., primary, Anto, J. M., additional, Akdis, M., additional, Auffray, C., additional, Keil, T., additional, Momas, I., additional, Postma, D.S., additional, Valenta, R., additional, Wickman, M., additional, Cambon‐Thomsen, A., additional, Haahtela, T., additional, Lambrecht, B. N., additional, Lodrup Carlsen, K. C., additional, Koppelman, G. H., additional, Sunyer, J., additional, Zuberbier, T., additional, Annesi‐Maesano, I., additional, Arno, A., additional, Bindslev‐Jensen, C., additional, De Carlo, G., additional, Forastiere, F., additional, Heinrich, J., additional, Kowalski, M. L., additional, Maier, D., additional, Melén, E., additional, Palkonen, S., additional, Smit, H. A., additional, Standl, M., additional, Wright, J., additional, Asarnoj, A., additional, Benet, M., additional, Ballardini, N., additional, Garcia‐Aymerich, J., additional, Gehring, U., additional, Guerra, S., additional, Hohman, C., additional, Kull, I., additional, Lupinek, C., additional, Pinart, M., additional, Skrindo, I., additional, Westman, M., additional, Smagghe, D., additional, Akdis, C., additional, Albang, R., additional, Anastasova, V., additional, Anderson, N., additional, Bachert, C., additional, Ballereau, S., additional, Ballester, F., additional, Basagana, X., additional, Bedbrook, A., additional, Bergstrom, A., additional, Berg, A., additional, Brunekreef, B., additional, Burte, E., additional, Carlsen, K. H., additional, Chatzi, L., additional, Coquet, J. M., additional, Curin, M., additional, Demoly, P., additional, Eller, E., additional, Fantini, M. P., additional, Gerhard, B., additional, Hammad, H., additional, Hertzen, L., additional, Hovland, V., additional, Jacquemin, B., additional, Just, J., additional, Keller, T., additional, Kerkhof, M., additional, Kiss, R., additional, Kogevinas, M., additional, Koletzko, S., additional, Lau, S., additional, Lehmann, I., additional, Lemonnier, N., additional, McEachan, R., additional, Mäkelä, M., additional, Mestres, J., additional, Minina, E., additional, Mowinckel, P., additional, Nadif, R., additional, Nawijn, M., additional, Oddie, S., additional, Pellet, J., additional, Pin, I., additional, Porta, D., additional, Rancière, F., additional, Rial‐Sebbag, A., additional, Saeys, Y., additional, Schuijs, M. J., additional, Siroux, V., additional, Tischer, C. G., additional, Torrent, M., additional, Varraso, R., additional, De Vocht, J., additional, Wenger, K., additional, Wieser, S., additional, and Xu, C., additional

Published
2016
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9. Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

Author

Andersen, M.R., Salazar, Margarita P., Schaap, Peter J., van de Vondervoort, Peter J. I., Culley, D., Thykaer, Jette, Frisvad, J.C., Nielsen, K.F., Albang, R., Albermann, Kaj, Berka, R.M., Braus, G.H., Braus-Stromeyer, S.A., Corrochano, L.M., Dai, Z., van Dijck, P.W.M., Hofmann, G., Lasure, Linda L., Magnuson, J.K., Menke, H., Meijer, M., Meijer, Susan L., Nielsen, J.T., Samson, R.A., Stam, H., Tsang, Adrian, van den Brink, J., Atkins, A., Aerts, A., Shapiro, Harris, Pangilinan, Jasmyn, Salamov, A., Lou, Yigong, Lindquist, E., Lucas, S., Grimwood, J., Grigoriev, I.V., Kubicek, Christian P., Martinez, Diego, van Peij, Noel N. M. E., Roubos, Johannes A., Nielsen, Jens, Baker, S.E., Andersen, M.R., Salazar, Margarita P., Schaap, Peter J., van de Vondervoort, Peter J. I., Culley, D., Thykaer, Jette, Frisvad, J.C., Nielsen, K.F., Albang, R., Albermann, Kaj, Berka, R.M., Braus, G.H., Braus-Stromeyer, S.A., Corrochano, L.M., Dai, Z., van Dijck, P.W.M., Hofmann, G., Lasure, Linda L., Magnuson, J.K., Menke, H., Meijer, M., Meijer, Susan L., Nielsen, J.T., Samson, R.A., Stam, H., Tsang, Adrian, van den Brink, J., Atkins, A., Aerts, A., Shapiro, Harris, Pangilinan, Jasmyn, Salamov, A., Lou, Yigong, Lindquist, E., Lucas, S., Grimwood, J., Grigoriev, I.V., Kubicek, Christian P., Martinez, Diego, van Peij, Noel N. M. E., Roubos, Johannes A., Nielsen, Jens, and Baker, S.E.

Published
2011

10. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

Author

Pel, H.J., Winde, J.H. de, Archer, D.B., Dyer, P.S., Hofmann, G., Schaap, P.J., Turner, G., Vries, R.P. de, Albang, R., Albermann, K., Andersen, M.R., Bendtsen, J.D., Benen, J.A., Berg, M. van den, Breestraat, S., Caddick, M.X., Contreras, R., Cornell, M., Coutinho, P.M., Danchin, E.G., Debets, A.J., Dekker, P., Dijck, P.W. van, Dijk, A. van, Dijkhuizen, L., Driessen, A.J., D'Enfert, C., Geysens, S., Goosen, C., Groot, G.S., Groot, P.W. de, Guillemette, T., Henrissat, B., Herweijer, M., Hombergh, J.P. van den, Hondel, C.A. van den, Heijden, R.T.J.M. van der, Kaaij, R.M. van der, Klis, F.M., Kools, H.J., Kubicek, C.P., Kuyk, P.A. van, Lauber, J., Lu, X., Maarel, M.J. van der, Meulenberg, R., Menke, H., Mortimer, M.A., Nielsen, J., Oliver, S.G., Olsthoorn, M., Pal, K., Peij, N.N. van, Ram, A.F., Rinas, U., Roubos, J.A., Sagt, C.M., Schmoll, M., Sun, J., Ussery, D., Varga, J., Vervecken, W., Vondervoort, P.J. van de, Wedler, H., Wosten, H.A., Zeng, A.P., Ooyen, A.J. van, Visser, J.C., Stam, H., Pel, H.J., Winde, J.H. de, Archer, D.B., Dyer, P.S., Hofmann, G., Schaap, P.J., Turner, G., Vries, R.P. de, Albang, R., Albermann, K., Andersen, M.R., Bendtsen, J.D., Benen, J.A., Berg, M. van den, Breestraat, S., Caddick, M.X., Contreras, R., Cornell, M., Coutinho, P.M., Danchin, E.G., Debets, A.J., Dekker, P., Dijck, P.W. van, Dijk, A. van, Dijkhuizen, L., Driessen, A.J., D'Enfert, C., Geysens, S., Goosen, C., Groot, G.S., Groot, P.W. de, Guillemette, T., Henrissat, B., Herweijer, M., Hombergh, J.P. van den, Hondel, C.A. van den, Heijden, R.T.J.M. van der, Kaaij, R.M. van der, Klis, F.M., Kools, H.J., Kubicek, C.P., Kuyk, P.A. van, Lauber, J., Lu, X., Maarel, M.J. van der, Meulenberg, R., Menke, H., Mortimer, M.A., Nielsen, J., Oliver, S.G., Olsthoorn, M., Pal, K., Peij, N.N. van, Ram, A.F., Rinas, U., Roubos, J.A., Sagt, C.M., Schmoll, M., Sun, J., Ussery, D., Varga, J., Vervecken, W., Vondervoort, P.J. van de, Wedler, H., Wosten, H.A., Zeng, A.P., Ooyen, A.J. van, Visser, J.C., and Stam, H.

Abstract

Contains fulltext : 51722.pdf (publisher's version ) (Closed access), The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.

Published
2007

12. Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

Author

Benet M, Albang R, Pinart M, Hohmann C, Tischer CG, Annesi-Maesano I, Baïz N, Bindslev-Jensen C, Lødrup Carlsen KC, Carlsen KH, Cirugeda L, Eller E, Fantini MP, Gehring U, Gerhard B, Gori D, Hallner E, Kull I, Lenzi J, McEachan R, Minina E, Momas I, Narduzzi S, Petherick ES, Porta D, Rancière F, Standl M, Torrent M, Wijga AH, Wright J, Kogevinas M, Guerra S, Sunyer J, Keil T, Bousquet J, Maier D, Anto JM, and Garcia-Aymerich J

Subjects
Child, Child, Preschool, Europe epidemiology, Female, Humans, Infant, Infant, Newborn, Male, Pregnancy, Asthma epidemiology, Cohort Studies, Hypersensitivity epidemiology, Research Design standards
Abstract

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Published
2019
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13. Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study.

Author

Pinart M, Albang R, Maier D, Duran-Tauleria E, Mena G, Gimeno-Santos E, Solà I, Garcia-Aymerich J, Guerra S, Stein RT, Benet M, Carlsen KH, Herr M, Jacquemin B, Momas I, Pin I, Rancière F, Smit HA, Varraso R, Bonfill X, Keil T, Bousquet J, and Antó JM

Subjects
Child, Humans, Hypersensitivity diagnosis, Hypersensitivity physiopathology, Hypersensitivity classification, Phenotype
Abstract

Background: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis., Methods: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers., Results: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%., Conclusions: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary., (© 2015 S. Karger AG, Basel.)

Published
2015
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14. Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88.

Author

Andersen MR, Salazar MP, Schaap PJ, van de Vondervoort PJ, Culley D, Thykaer J, Frisvad JC, Nielsen KF, Albang R, Albermann K, Berka RM, Braus GH, Braus-Stromeyer SA, Corrochano LM, Dai Z, van Dijck PW, Hofmann G, Lasure LL, Magnuson JK, Menke H, Meijer M, Meijer SL, Nielsen JB, Nielsen ML, van Ooyen AJ, Pel HJ, Poulsen L, Samson RA, Stam H, Tsang A, van den Brink JM, Atkins A, Aerts A, Shapiro H, Pangilinan J, Salamov A, Lou Y, Lindquist E, Lucas S, Grimwood J, Grigoriev IV, Kubicek CP, Martinez D, van Peij NN, Roubos JA, Nielsen J, and Baker SE

Subjects
Base Sequence, Gene Expression Profiling, Gene Rearrangement genetics, Gene Transfer, Horizontal genetics, Genomics methods, Molecular Sequence Data, Polymorphism, Single Nucleotide genetics, Sequence Analysis, DNA, Species Specificity, Synteny genetics, Aspergillus niger genetics, Computational Biology methods, Evolution, Molecular, Genetic Variation, Genome, Fungal genetics, Phylogeny
Abstract

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.

Published
2011
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15. Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.

Author

van den Berg MA, Albang R, Albermann K, Badger JH, Daran JM, Driessen AJ, Garcia-Estrada C, Fedorova ND, Harris DM, Heijne WH, Joardar V, Kiel JA, Kovalchuk A, Martín JF, Nierman WC, Nijland JG, Pronk JT, Roubos JA, van der Klei IJ, van Peij NN, Veenhuis M, von Döhren H, Wagner C, Wortman J, and Bovenberg RA

Subjects
Base Sequence, Molecular Sequence Data, Sequence Analysis, DNA methods, Chromosome Mapping methods, Fungal Proteins genetics, Genome, Fungal genetics, Penicillin G metabolism, Penicillium chrysogenum genetics, Transcription Factors genetics
Abstract

Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.

Published
2008
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16. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88.

Author

Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, Turner G, de Vries RP, Albang R, Albermann K, Andersen MR, Bendtsen JD, Benen JA, van den Berg M, Breestraat S, Caddick MX, Contreras R, Cornell M, Coutinho PM, Danchin EG, Debets AJ, Dekker P, van Dijck PW, van Dijk A, Dijkhuizen L, Driessen AJ, d'Enfert C, Geysens S, Goosen C, Groot GS, de Groot PW, Guillemette T, Henrissat B, Herweijer M, van den Hombergh JP, van den Hondel CA, van der Heijden RT, van der Kaaij RM, Klis FM, Kools HJ, Kubicek CP, van Kuyk PA, Lauber J, Lu X, van der Maarel MJ, Meulenberg R, Menke H, Mortimer MA, Nielsen J, Oliver SG, Olsthoorn M, Pal K, van Peij NN, Ram AF, Rinas U, Roubos JA, Sagt CM, Schmoll M, Sun J, Ussery D, Varga J, Vervecken W, van de Vondervoort PJ, Wedler H, Wösten HA, Zeng AP, van Ooyen AJ, Visser J, and Stam H

Subjects
Base Sequence, Molecular Sequence Data, Aspergillus niger genetics, Chromosome Mapping, Chromosomes, Fungal genetics, Genome, Fungal genetics, Plant Proteins genetics, Sequence Analysis, DNA methods
Abstract

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.

Published
2007
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17. Negative regulatory element in the mammary specific whey acidic protein promoter.

Author

Kolb AF, Günzburg WH, Albang R, Brem G, Erfle V, and Salmons B

Subjects
Animals, Base Sequence, Cell Line, Cell Nucleus metabolism, Coleoptera, DNA Mutational Analysis, DNA Primers, Gene Expression Regulation, Growth Hormone biosynthesis, Humans, Luciferases biosynthesis, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Organ Specificity, Plasmids, Polymerase Chain Reaction, Recombinant Proteins biosynthesis, Restriction Mapping, Sequence Homology, Nucleic Acid, Transcription, Genetic, Transfection, Milk Proteins biosynthesis, Milk Proteins genetics, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid
Abstract

Expression of the whey acidic protein (WAP) gene is tightly regulated in a tissue and developmental stage specific manner, in that the WAP gene is exclusively expressed in the mammary gland during pregnancy and lactation. Using both deletion and competition analyses, evidence is provided for the existence of a negative regulatory element (NRE) in the WAP promoter located between -413 and -93 with respect to the WAP transcriptional initiation site. This NRE dramatically decreases transcription from linked heterologous promoter-reporter gene constructs. The activity of NRE requires WAP promoter sequences that are 230 bp apart since subfragments of the NRE fail to inhibit transcription of adjoining reporter genes. Nuclear extracts from different cell types, in which the WAP gene is not active, contain a protein or complex that specifically interacts with the entire NRE but not with subfragments of it. The contact points between this protein (NRE binding factor [NBF]) and the NRE element have been partially determined. Mutation of the implicated nucleotides severely reduces the ability of NBF to bind, and such mutated promoter fragments fail to alleviate transcriptional repression in competition experiments. This suggests that NBF binding to the NRE is at least in part responsible for the negative regulation of the WAP promoter. Since NBF is not detectable in the lactating mammary gland, where the WAP gene is expressed, we speculate that it may be a determinant of the expression spectrum of the WAP gene.

Published
1994
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