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1. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Pei, J., Schuldt, M., Nagyova, E., Gu, Z., el Bouhaddani, S., Yiangou, L., Jansen, M., Calis, J. J. A., Dorsch, L. M., Blok, C. Snijders, van den Dungen, N. A. M., Lansu, N., Boukens, B. J., Efimov, I. R., Michels, M., Verhaar, M. C., de Weger, R., Vink, A., van Steenbeek, F. G., Baas, A. F., Davis, R. P., Uh, H. W., Kuster, D. W. D., Cheng, C., Mokry, M., van der Velden, J., Asselbergs, F. W., and Harakalova, M.

Published
2021
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2. Molecular Diagnostics in Pathology

Author

Hinrichs, J. W. J., de Weger, R. A., van Blokland, W. T. M., Offerhaus, G. J. A., van Diest, P. J., van Pelt-Verkuil, E., editor, van Leeuwen, W.B., editor, and te Witt, R., editor

Published
2017
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7. Follicular Dendritic Cells and Infection by Human Immunodeficiency Virus Type 1—A Crucial Target Cell and Virus Reservoir

Author

Schuurman, H.-J., Joling, P., van Wichen, D. F., Rademakers, L. H. P. M., Broekhuizen, R., de Weger, R. A., van den Tweel, J. G., Goudsmit, J., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, and Kosco-Vilbois, Marie H., editor

Published
1995
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13. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, Harakalova, M, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, and Harakalova, M

Abstract

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts.RESULTS: Using H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations.CONCLUSIONS: By integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets.

Published
2021

14. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Afd Pharmacoepi & Clinical Pharmacology, Interne geneeskunde GD, dCSCA AVR, Sub Inorganic Chemistry and Catalysis, LS Vertaalwetenschap, CS_Genetics, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, Harakalova, M, Afd Pharmacoepi & Clinical Pharmacology, Interne geneeskunde GD, dCSCA AVR, Sub Inorganic Chemistry and Catalysis, LS Vertaalwetenschap, CS_Genetics, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, and Harakalova, M

Published
2021

15. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Onderzoek Precision medicine, Other research (not in main researchprogram), Biostatistiek Onderzoek, Genetica Klinische Genetica, Immuno/reuma onderzoek 5 (Vastert2), CMM Groep Cuppen, Unit Opleiding Aios, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, JC onderzoeksprogramma Methodologie, Onderzoek, Child Health, Team Medisch, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, Harakalova, M, Onderzoek Precision medicine, Other research (not in main researchprogram), Biostatistiek Onderzoek, Genetica Klinische Genetica, Immuno/reuma onderzoek 5 (Vastert2), CMM Groep Cuppen, Unit Opleiding Aios, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, JC onderzoeksprogramma Methodologie, Onderzoek, Child Health, Team Medisch, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, and Harakalova, M

Published
2021

16. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation

Author

Lion, T, Watzinger, F, Preuner, S, Kreyenberg, H, Tilanus, M, de Weger, R, van Loon, J, de Vries, L, Cavé, H, Acquaviva, C, Lawler, M, Crampe, M, Serra, A, Saglio, B, Colnaghi, F, Biondi, A, van Dongen, J J M, van der Burg, M, Gonzalez, M, Alcoceba, M, Barbany, G, Hermanson, M, Roosnek, E, Steward, C, Harvey, J, Frommlet, F, and Bader, P

Published
2012
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23. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

Author

Pei, JY, Harakalova, M, Treibel, TA, Lumbers, RT, Boukens, BJ, Efimov, IR, van Dinter, JT, Gonzalez, A, Lopez, B, el Azzouzi, H, van den Dungen, N, van Dijk, CGM, Krebber, M M, den Ruijter, HM, Pasterkamp, G, Duncker, Dirk-jan, Nieuwenhuis, EES, de Weger, R, Huibers, MMH, Vink, A, Moore, JH, Moon, JC, Verhaar, MC, Kararigas, G, Mokry, M, Asselbergs, FW, Cheng, Caroline, Pei, JY, Harakalova, M, Treibel, TA, Lumbers, RT, Boukens, BJ, Efimov, IR, van Dinter, JT, Gonzalez, A, Lopez, B, el Azzouzi, H, van den Dungen, N, van Dijk, CGM, Krebber, M M, den Ruijter, HM, Pasterkamp, G, Duncker, Dirk-jan, Nieuwenhuis, EES, de Weger, R, Huibers, MMH, Vink, A, Moore, JH, Moon, JC, Verhaar, MC, Kararigas, G, Mokry, M, Asselbergs, FW, and Cheng, Caroline

Published
2020

24. Plasma Immunoglobulin Levels Prior to Cardiac Transplantation are Associated with Post-Transplantation Survival

Author

Onderzoek Molecular Cardiology, Experimentele Afd. Cardiologie 2, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Pathologie Pathologen staf, van den Hoogen, P., Huibers, M. M., van den Dolder, F. W., de Weger, R. A., Siera, E., de Jonge, N., Doevendans, P. A., Sluijter, J. P., de Jager, S. C., Vink, A., Onderzoek Molecular Cardiology, Experimentele Afd. Cardiologie 2, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Pathologie Pathologen staf, van den Hoogen, P., Huibers, M. M., van den Dolder, F. W., de Weger, R. A., Siera, E., de Jonge, N., Doevendans, P. A., Sluijter, J. P., de Jager, S. C., and Vink, A.

Published
2020

31. Health-related quality of life in multiple myeloma and mapping algorithms to derive health-state utility values: an overview

Author

Qerimi Rushaj, V, Jahn, B, Puntscher, S, Stojkov, I, Manca, A, Holzner, B, Gamper, E, Willenbacher, W, Kemmler, G, Weger, R, Neppl, L, Greenberg, D, Siebert, U, and Rochau, U

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background/research question: Health-related quality of life (HRQoL) and health-state utility values (HSUVs) are measured with different methods and instruments. Deriving HSUVs from generic preference-based instruments (e.g., EQ-5D, SF-6D, HUI) is recommended by academic institutions, HTA agencies[for full text, please go to the a.m. URL], EbM und Digitale Transformation in der Medizin; 20. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2019
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35. Effectiveness of treatment sequences for elderly patients with multiple myeloma - a comparison of treatment schedules from clinical trials and experience from the Austrian Myeloma Registry

Author

Rochau, U, Vukicevic, D, Angerer, S, Schaffner, M, Qerimi Rushaj, V, Conrads-Frank, A, Jahn, B, Hackl, WO, Ammenwerth, E, Stummer, H, Garrison, LP, Weger, R, Willenbacher, E, Willenbacher, W, Siebert, U, Rochau, U, Vukicevic, D, Angerer, S, Schaffner, M, Qerimi Rushaj, V, Conrads-Frank, A, Jahn, B, Hackl, WO, Ammenwerth, E, Stummer, H, Garrison, LP, Weger, R, Willenbacher, E, Willenbacher, W, and Siebert, U

Published
2019

36. Clinical versus histological grading in the assessment of cutaneous graft versus host disease

Author

Afdeling Hematologie, Other research (not in main researchprogram), Pathologie Pathologen staf, Cancer, Pathologie Cytologie, Pathologie Moleculair, Circulatory Health, CTI Kuball, MS Hematologie, Regenerative Medicine and Stem Cells, Infection & Immunity, Pathologie, Hogenes, M. C.H., Te Boome, L. C.J., Van Der Valk, D. C., Van Dijk, M. R., De Weger, R. A., Kuball, J., Van Diest, P. J., Afdeling Hematologie, Other research (not in main researchprogram), Pathologie Pathologen staf, Cancer, Pathologie Cytologie, Pathologie Moleculair, Circulatory Health, CTI Kuball, MS Hematologie, Regenerative Medicine and Stem Cells, Infection & Immunity, Pathologie, Hogenes, M. C.H., Te Boome, L. C.J., Van Der Valk, D. C., Van Dijk, M. R., De Weger, R. A., Kuball, J., and Van Diest, P. J.

Published
2019

45. Mapping Health-Related Quality of Life in Multiple Myeloma: Assessment of Existing Mapping Algorithms

Author

Qerimi, V, Jahn, B, Puntscher, S, Manca, A, Holzner, B, Gamper, E, Willenbacher, W, Weger, R, Neppl, L, Greenberg, D, Siebert, U, and Rochau, U

Subjects
ddc: 610, 610 Medical sciences, Medicine, health care economics and organizations
Abstract

Background: The National Institute for Clinical Excellence (NICE) recommends quality-adjusted life years as the main measure for health outcomes in cost-utility analyses (CUAs). In the absence of health utility values (HUVs), NICE recommends to use “mapping” functions to link outcomes [for full text, please go to the a.m. URL], Brücken bauen – von der Evidenz zum Patientenwohl; 19. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2018
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46. PCN163 SEQUENTIAL TREATMENT REGIMENS FOR ELDERLY PATIENTS WITH MULTIPLE MYELOMA: A COST-EFFECTIVENESS ANALYSIS INCLUDING EXPERIENCE FROM REAL-WORLD DATA

Author

Rochau, U., primary, Vukićević, D., additional, Angerer, S., additional, Schaffner, M., additional, Qerimi Rushaj, V., additional, Conrads-Frank, A., additional, Jahn, B., additional, Hackl, W.O., additional, Ammenwerth, E., additional, Stummer, H., additional, Garrison, L.P., additional, Weger, R., additional, Willenbacher, E., additional, Willenbacher, W., additional, and Siebert, U., additional

Published
2019
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