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1. Privacy-Preserving Multi-Center Differential Protein Abundance Analysis with FedProt

Author

Burankova, Yuliya, Abele, Miriam, Bakhtiari, Mohammad, von Törne, Christine, Barth, Teresa, Schweizer, Lisa, Giesbertz, Pieter, Schmidt, Johannes R., Kalkhof, Stefan, Müller-Deile, Janina, van Veelen, Peter A, Mohammed, Yassene, Hammer, Elke, Arend, Lis, Adamowicz, Klaudia, Laske, Tanja, Hartebrodt, Anne, Frisch, Tobias, Meng, Chen, Matschinske, Julian, Späth, Julian, Röttger, Richard, Schwämmle, Veit, Hauck, Stefanie M., Lichtenthaler, Stefan, Imhof, Axel, Mann, Matthias, Ludwig, Christina, Kuster, Bernhard, Baumbach, Jan, and Zolotareva, Olga

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Machine Learning
Abstract

Quantitative mass spectrometry has revolutionized proteomics by enabling simultaneous quantification of thousands of proteins. Pooling patient-derived data from multiple institutions enhances statistical power but raises significant privacy concerns. Here we introduce FedProt, the first privacy-preserving tool for collaborative differential protein abundance analysis of distributed data, which utilizes federated learning and additive secret sharing. In the absence of a multicenter patient-derived dataset for evaluation, we created two, one at five centers from LFQ E.coli experiments and one at three centers from TMT human serum. Evaluations using these datasets confirm that FedProt achieves accuracy equivalent to DEqMS applied to pooled data, with completely negligible absolute differences no greater than $\text{$4 \times 10^{-12}$}$. In contrast, -log10(p-values) computed by the most accurate meta-analysis methods diverged from the centralized analysis results by up to 25-27. FedProt is available as a web tool with detailed documentation as a FeatureCloud App., Comment: 52 pages, 16 figures, 12 tables. Last two authors listed are joint last authors

Published
2024

2. Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks

Author

Delgado de la Herran, Hilda, Vecellio Reane, Denis, Cheng, Yiming, Katona, Máté, Hosp, Fabian, Greotti, Elisa, Wettmarshausen, Jennifer, Patron, Maria, Mohr, Hermine, Prudente de Mello, Natalia, Chudenkova, Margarita, Gorza, Matteo, Walia, Safal, Feng, Michael Sheng-Fu, Leimpek, Anja, Mielenz, Dirk, Pellegata, Natalia S, Langer, Thomas, Hajnóczky, György, Mann, Matthias, Murgia, Marta, and Perocchi, Fabiana

Published
2024
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3. Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity

Author

Jiang, Shan, Yuan, Taolin, Rosenberger, Florian A., Mourier, Arnaud, Dragano, Nathalia R. V., Kremer, Laura S., Rubalcava-Gracia, Diana, Hansen, Fynn M., Borg, Melissa, Mennuni, Mara, Filograna, Roberta, Alsina, David, Misic, Jelena, Koolmeister, Camilla, Papadea, Polyxeni, de Angelis, Martin Hrabe, Ren, Lipeng, Andersson, Olov, Unger, Anke, Bergbrede, Tim, Di Lucrezia, Raffaella, Wibom, Rolf, Zierath, Juleen R., Krook, Anna, Giavalisco, Patrick, Mann, Matthias, and Larsson, Nils-Göran

Published
2024
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6. Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

Author

Nygaard, Ulrikka, Nielsen, Annelaura Bach, Dungu, Kia Hee Schultz, Drici, Lylia, Holm, Mette, Ottenheijm, Maud Eline, Nielsen, Allan Bybeck, Glenthøj, Jonathan Peter, Schmidt, Lisbeth Samsø, Cortes, Dina, Jørgensen, Inger Merete, Mogensen, Trine Hyrup, Schmiegelow, Kjeld, Mann, Matthias, Vissing, Nadja Hawwa, and Wewer Albrechtsen, Nicolai J.

Published
2024
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8. Author Correction: Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification

Author

Tretter, Celina, de Andrade Krätzig, Niklas, Pecoraro, Matteo, Lange, Sebastian, Seifert, Philipp, von Frankenberg, Clara, Untch, Johannes, Zuleger, Gabriela, Wilhelm, Mathias, Zolg, Daniel P., Dreyer, Florian S., Bräunlein, Eva, Engleitner, Thomas, Uhrig, Sebastian, Boxberg, Melanie, Steiger, Katja, Slotta-Huspenina, Julia, Ochsenreither, Sebastian, von Bubnoff, Nikolas, Bauer, Sebastian, Boerries, Melanie, Jost, Philipp J., Schenck, Kristina, Dresing, Iska, Bassermann, Florian, Friess, Helmut, Reim, Daniel, Grützmann, Konrad, Pfütze, Katrin, Klink, Barbara, Schröck, Evelin, Haller, Bernhard, Kuster, Bernhard, Mann, Matthias, Weichert, Wilko, Fröhling, Stefan, Rad, Roland, Hiltensperger, Michael, and Krackhardt, Angela M.

Published
2024
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10. Concept and feasibility of the Augsburg Longitudinal Plasma Study (ALPS) – a prospective trial for comprehensive liquid biopsy-based longitudinal monitoring of solid cancer patients

Author

Sommer Sebastian, Schmutz Maximilian, Hildebrand Kathrin, Schiwitza Annett, Benedikt Selinah, Eberle Maria, Mögele Tatiana, Sultan Aziz, Reichl Lena, Campillo Maria, Uhrmacher Luise, Nikolic Ana Antic, Bundschuh Ralph, Lapa Constantin, Kuhlen Michaela, Dintner Sebastian, Langer Angela, Märkl Bruno, Wendler Thomas, Tehlan Kartikay, Kröncke Thomas, Wahle Maria, Mann Matthias, Casadei Nicolas, Pogoda Michaela, Hummler Simone, Sax Irmengard, Schlesner Matthias, Kubuschok Boris, Trepel Martin, and Claus Rainer

Subjects
liquid biopsy, ctdna, longitudinal profiling, clonal evolution, spatial heterogeneity, translational research, Medical technology, R855-855.5
Abstract

Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution.

Published
2024
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11. Adamts12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts

Author

Hoeft, Konrad, Koch, Lars, Ziegler, Susanne, Zhang, Ling, Luetke, Steffen, Tanzer, Maria C., Mohanta, Debashish, Schumacher, David, Schreibing, Felix, Long, Qingqing, Kim, Hyojin, Klinkhammer, Barbara M., Schikarski, Carla, Maryam, Sidrah, Baens, Mathijs, Hermann, Juliane, Krieg, Sarah, Peisker, Fabian, De Laporte, Laura, Schaefer, Gideon J.L., Menzel, Sylvia, Jankowski, Joachim, Humphreys, Benjamin D., Wahida, Adam, Schneider, Rebekka K., Versele, Matthias, Boor, Peter, Mann, Matthias, Sengle, Gerhard, Hayat, Sikander, and Kramann, Rafael

Subjects
Medical research, Medicine, Experimental, Fibrosis -- Physiological aspects, Proteases -- Physiological aspects, Extracellular matrix -- Physiological aspects, Fibroblasts -- Physiological aspects -- Health aspects, Wounds and injuries -- Physiological aspects
Abstract

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury- responsive fibroblast subset defined by aberrant high JAK/STAT signaling., Introduction Fibrosis represents the uncontrolled replacement of parenchymal tissue by extracellular matrix (ECM) (1). Whereas deposition of ECM sustains tissue integrity immediately after injury, continued deposition of ECM by myofibroblasts [...]

Published
2024
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12. Democratising Knowledge Representation with BioCypher

Author

Lobentanzer, Sebastian, Aloy, Patrick, Baumbach, Jan, Bohar, Balazs, Charoentong, Pornpimol, Danhauser, Katharina, Doğan, Tunca, Dreo, Johann, Dunham, Ian, Fernandez-Torras, Adrià, Gyori, Benjamin M., Hartung, Michael, Hoyt, Charles Tapley, Klein, Christoph, Korcsmaros, Tamas, Maier, Andreas, Mann, Matthias, Ochoa, David, Pareja-Lorente, Elena, Popp, Ferdinand, Preusse, Martin, Probul, Niklas, Schwikowski, Benno, Sen, Bünyamin, Strauss, Maximilian T., Turei, Denes, Ulusoy, Erva, Wodke, Judith Andrea Heidrun, and Saez-Rodriguez, Julio

Subjects
Quantitative Biology - Molecular Networks
Abstract

Standardising the representation of biomedical knowledge among all researchers is an insurmountable task, hindering the effectiveness of many computational methods. To facilitate harmonisation and interoperability despite this fundamental challenge, we propose to standardise the framework of knowledge graph creation instead. We implement this standardisation in BioCypher, a FAIR (findable, accessible, interoperable, reusable) framework to transparently build biomedical knowledge graphs while preserving provenances of the source data. Mapping the knowledge onto biomedical ontologies helps to balance the needs for harmonisation, human and machine readability, and ease of use and accessibility to non-specialist researchers. We demonstrate the usefulness of this framework on a variety of use cases, from maintenance of task-specific knowledge stores, to interoperability between biomedical domains, to on-demand building of task-specific knowledge graphs for federated learning. BioCypher (https://biocypher.org) frees up valuable developer time; we encourage further development and usage by the community., Comment: 34 pages, 6 figures; submitted to Nature Biotechnology

Published
2022

13. Profiling the human intestinal environment under physiological conditions

Author

Shalon, Dari, Culver, Rebecca Neal, Grembi, Jessica A, Folz, Jacob, Treit, Peter V, Shi, Handuo, Rosenberger, Florian A, Dethlefsen, Les, Meng, Xiandong, Yaffe, Eitan, Aranda-Díaz, Andrés, Geyer, Philipp E, Mueller-Reif, Johannes B, Spencer, Sean, Patterson, Andrew D, Triadafilopoulos, George, Holmes, Susan P, Mann, Matthias, Fiehn, Oliver, Relman, David A, and Huang, Kerwyn Casey

Subjects
Clinical Research, Digestive Diseases, Underpinning research, 1.1 Normal biological development and functioning, Oral and gastrointestinal, Humans, Bile Acids and Salts, Gastrointestinal Microbiome, Metabolome, Proteome, Bacteria, Bacteriophages, Feces, Intestines, Digestion, General Science & Technology
Abstract

The spatiotemporal structure of the human microbiome1,2, proteome3 and metabolome4,5 reflects and determines regional intestinal physiology and may have implications for disease6. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals7. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

Published
2023

14. The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions

Author

Garvanska, Dimitriya H, Alvarado, R Elias, Mundt, Filip Oskar, Lindqvist, Richard, Duel, Josephine Kerzel, Coscia, Fabian, Nilsson, Emma, Lokugamage, Kumari, Johnson, Bryan A, Plante, Jessica A, Morris, Dorothea R, Vu, Michelle N, Estes, Leah K, McLeland, Alyssa M, Walker, Jordyn, Crocquet-Valdes, Patricia A, Mendez, Blanca Lopez, Plante, Kenneth S, Walker, David H, Weisser, Melanie Bianca, Överby, Anna K, Mann, Matthias, Menachery, Vineet D, and Nilsson, Jakob

Published
2024
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18. List of contributors

Author

Ahn, Joseph C., primary, Anand, Shankara, additional, Arnaout, O., additional, Bandyopadhyay, Anuja, additional, Bartholomew, Erin, additional, Bates, David W., additional, Bender, Sarah M.L., additional, Bhullar, Puneet K., additional, Bhutani, Tina, additional, Boaro, A., additional, Boyer, Edward W., additional, Brown, Ethan D.L., additional, Carreiro, Stephanie, additional, Chahla, Jorge, additional, Chandran, Viji Pulikkel, additional, Cheng, Ching-Yu, additional, Cheung, Carol Y., additional, Choudhary, Anirudh, additional, Choudhury, Avishek, additional, Chung, Mimi, additional, Ciurtin, Coziana, additional, Comfere, Nneka I., additional, Corriveau-Lecavalier, Nick, additional, Côté, Mélina, additional, del Alamo, Diego, additional, Dias, Roger D., additional, Dönnes, Pierre, additional, Duong, Dat, additional, Ebnali, Mahdi, additional, El Sherbini, Adham, additional, ElZarrad, M. Khair, additional, Fakhouri, Tala H., additional, Fakhoury, Marc, additional, Fein, Joshua A., additional, Fischer, Uwe M., additional, Glicksberg, Benjamin S., additional, Goldstein, Cathy, additional, Gonem, Sherif, additional, Green, Darren V.S., additional, Gupta, Raghav, additional, Hakimi, Marwa, additional, Halamka, John D., additional, Han, Christina S., additional, Hannah-Shmouni, Fady, additional, Harrer, Stefan, additional, Hazime, Ali Amer, additional, Howard, Michael A., additional, Hui, Herbert Y.H., additional, Ildardashty, Alexander, additional, J.F. Shaikh, Hashim, additional, Jeliazkov, Jeliazko R., additional, Jones, David T., additional, Juhn, Young J., additional, Jury, Elizabeth C., additional, Kandaswamy, Swaminathan, additional, Kang, Yanna, additional, Kann, Benjamin H., additional, Kaplin, Scott, additional, Karpiak, Joel, additional, Kassir, Elias, additional, Kaur, Harsimran, additional, Khan, Sohil, additional, Khatib, Reem, additional, Kherabi, Yousra, additional, Knake, Lindsey A., additional, Krittanawong, Chayakrit, additional, Kuhn, Veronica C., additional, Kunze, Kyle, additional, Lamarche, Benoît, additional, Laplante, Simon, additional, Lehmann, Lisa Soleymani, additional, Li, Dawei, additional, Liao, Wilson, additional, Likitlersuang, Jirapat, additional, Liu, Qi, additional, Madani, Amin, additional, Malik, Momin M., additional, Mann, Matthias, additional, Masood, Sameer, additional, Mathur, Piyush, additional, McManus, Sean, additional, Menard, Jeffrey, additional, Mivalt, Filip, additional, Murphree, Dennis, additional, Myers, Thomas G., additional, Narayan, Sanjiv M., additional, Natarajan, Vivek, additional, Pandav, Krunal, additional, Parwani, Anil V., additional, Pedraza Bermeo, Adriana Marcela, additional, Peiffer-Smadja, Nathan, additional, Peng, Junjie, additional, Peng, Lily, additional, Peters, Margot S., additional, Petrick, Nicholas, additional, Polce, Evan, additional, Poojari, Pooja Gopal, additional, Price, W. Nicholson, additional, Raghavan, Lavanya, additional, Rajan, Asha K., additional, Ran, An Ran, additional, Rangu, Sowmith, additional, Rashid, Muhammed, additional, Reddy, Charitha D., additional, Rider, Nicholas L., additional, Rigatti, Marc, additional, Rivers, Michael, additional, Robinson, George, additional, Rogers, Albert J., additional, Rogerson, Colin M., additional, Ryu, Euijung, additional, Sahiner, Berkman, additional, Sarnaik, Kunaal, additional, Shafi, Saba, additional, Shah, Vijay H., additional, Shapovalov, Maxim V., additional, Sharma, Samin K, additional, Shekhar, Skand, additional, Shin, Harold, additional, Shouval, Roni, additional, Smith, Kenneth, additional, Sokumbi, Olayemi, additional, Solomon, Benjamin D., additional, Somani, Sulaiman S., additional, Sternke, Matt C., additional, Strauss, Maximillian T., additional, Syrowatka, Ania, additional, Tang, W. H. Wilson, additional, Teven, Chad M., additional, Tewari, Ashutosh Kumar, additional, Thunga, Girish, additional, Urena, Estefania, additional, Verma, Ashish, additional, Vietas, Jay, additional, Waikel, Rebekah L., additional, Wi, Chung-Il, additional, Winter, Meredith C., additional, Wong, Melissa S., additional, Wong, Tien Yin, additional, Wu, Chao-Ping, additional, Yeroushalmi, Samuel, additional, Zenati, Marco A., additional, Zeng, Wen-Feng, additional, and Zheng, Yingfeng, additional

Published
2024
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24. Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases

Author

Hansen, Torben, Mann, Matthias, Matthijnssens, Jelle, Krag, Aleksander, Bork, Peer, Arumugam, Manimozhiyan, Trebicka, Jonel, Karsdal, Morten, Anastasiadou, Ema, Israelsen, Hans, Melberg, Hans Olav, Legido-Quigley, Cristina, Thiele, Maja, Villesen, Ida Falk, Niu, Lili, Johansen, Stine, Sulek, Karolina, Nishijima, Suguru, Espen, Lore Van, Keller, Marisa, Israelsen, Mads, Suvitaival, Tommi, Zawadzki, Andressa de, Juel, Helene Bæk, Brol, Maximilian Joseph, Stinson, Sara Elizabeth, Huang, Yun, Silva, Maria Camilla Alvarez, Kuhn, Michael, Leeming, Diana Julie, Dalgaard, Louise Torp, and Jensen, Lars Juhl

Published
2024
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27. Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia

Author

Tubío-Santamaría, Nuria, Jayavelu, Ashok Kumar, Schnoeder, Tina M., Eifert, Theresa, Hsu, Chen-Jen, Perner, Florian, Zhang, Qirui, Wenge, Daniela V., Hansen, Fynn M., Kirkpatrick, Joanna M., Jyotsana, Nidhi, Lane, Steven W., von Eyss, Björn, Deshpande, Aniruddha J., Kühn, Michael W. M., Schwaller, Juerg, Cammann, Clemens, Seifert, Ulrike, Ebstein, Frédéric, Krüger, Elke, Hochhaus, Andreas, Heuser, Michael, Ori, Alessandro, Mann, Matthias, Armstrong, Scott A., and Heidel, Florian H.

Published
2023
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28. A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease

Author

Schmidt, Sebastian, Stautner, Constantin, Vu, Duc Tung, Heinz, Alexander, Regensburger, Martin, Karayel, Ozge, Trümbach, Dietrich, Artati, Anna, Kaltenhäuser, Sabine, Nassef, Mohamed Zakaria, Hembach, Sina, Steinert, Letyfee, Winner, Beate, Jürgen, Winkler, Jastroch, Martin, Luecken, Malte D., Theis, Fabian J., Westmeyer, Gil Gregor, Adamski, Jerzy, Mann, Matthias, Hiller, Karsten, Giesert, Florian, Vogt Weisenhorn, Daniela M., and Wurst, Wolfgang

Published
2023
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29. Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification

Author

Tretter, Celina, de Andrade Krätzig, Niklas, Pecoraro, Matteo, Lange, Sebastian, Seifert, Philipp, von Frankenberg, Clara, Untch, Johannes, Zuleger, Gabriela, Wilhelm, Mathias, Zolg, Daniel P., Dreyer, Florian S., Bräunlein, Eva, Engleitner, Thomas, Uhrig, Sebastian, Boxberg, Melanie, Steiger, Katja, Slotta-Huspenina, Julia, Ochsenreither, Sebastian, von Bubnoff, Nikolas, Bauer, Sebastian, Boerries, Melanie, Jost, Philipp J., Schenck, Kristina, Dresing, Iska, Bassermann, Florian, Friess, Helmut, Reim, Daniel, Grützmann, Konrad, Pfütze, Katrin, Klink, Barbara, Schröck, Evelin, Haller, Bernhard, Kuster, Bernhard, Mann, Matthias, Weichert, Wilko, Fröhling, Stefan, Rad, Roland, Hiltensperger, Michael, and Krackhardt, Angela M.

Published
2023
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31. The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs

Author

Herchenröther, Andreas, Gossen, Stefanie, Friedrich, Tobias, Reim, Alexander, Daus, Nadine, Diegmüller, Felix, Leers, Jörg, Sani, Hakimeh Moghaddas, Gerstner, Sarah, Schwarz, Leah, Stellmacher, Inga, Szymkowiak, Laura Victoria, Nist, Andrea, Stiewe, Thorsten, Borggrefe, Tilman, Mann, Matthias, Mackay, Joel P., Bartkuhn, Marek, Borchers, Annette, Lan, Jie, and Hake, Sandra B.

Published
2023
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33. Democratizing knowledge representation with BioCypher

Author

Lobentanzer, Sebastian, Aloy, Patrick, Baumbach, Jan, Bohar, Balazs, Carey, Vincent J., Charoentong, Pornpimol, Danhauser, Katharina, Doğan, Tunca, Dreo, Johann, Dunham, Ian, Farr, Elias, Fernandez-Torras, Adrià, Gyori, Benjamin M., Hartung, Michael, Hoyt, Charles Tapley, Klein, Christoph, Korcsmaros, Tamas, Maier, Andreas, Mann, Matthias, Ochoa, David, Pareja-Lorente, Elena, Popp, Ferdinand, Preusse, Martin, Probul, Niklas, Schwikowski, Benno, Sen, Bünyamin, Strauss, Maximilian T., Turei, Denes, Ulusoy, Erva, Waltemath, Dagmar, Wodke, Judith A. H., and Saez-Rodriguez, Julio

Published
2023
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34. Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia

Author

Felipe Fumero, Eloísa, Walter, Carolin, Frenz, Joris Maximillian, Seifert, Franca, Alla, Vijay, Hennig, Thorben, Angenendt, Linus, Hartmann, Wolfgang, Wolf, Sebastian, Serve, Hubert, Oellerich, Thomas, Lenz, Georg, Müller-Tidow, Carsten, Schliemann, Christoph, Huber, Otmar, Dugas, Martin, Mann, Matthias, Jayavelu, Ashok Kumar, Mikesch, Jan-Henrik, and Arteaga, Maria Francisca

Published
2024
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36. Mustn1 is a smooth muscle cell-secreted microprotein that modulates skeletal muscle extracellular matrix composition

Author

Ducommun, Serge, Jannig, Paulo R., Cervenka, Igor, Murgia, Marta, Mittenbühler, Melanie J., Chernogubova, Ekaterina, Dias, José M., Jude, Baptiste, Correia, Jorge C., Van Vranken, Jonathan G., Ocana-Santero, Gabriel, Porsmyr-Palmertz, Margareta, McCann Haworth, Sarah, Martínez-Redondo, Vicente, Liu, Zhengye, Carlström, Mattias, Mann, Matthias, Lanner, Johanna T., Teixeira, Ana I., Maegdefessel, Lars, Spiegelman, Bruce M., and Ruas, Jorge L.

Published
2024
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38. Molecular origin of blood-based infrared fingerprints

Author

Voronina, Liudmila, Leonardo, Cristina, Mueller-Reif, Johannes B., Geyer, Philipp E., Huber, Marinus, Trubetskov, Michael, Kepesidis, Kosmas V., Behr, Jurgen, Mann, Matthias, Krausz, Ferenc, and Zigman, Mihaela

Subjects
Physics - Chemical Physics
Abstract

Previous studies demonstrated that infrared absorption spectra of blood sera may help disease detection. For clinical translation of this approach, it is important to determine the molecular origin of disease-related spectral perturbations. To that end, we supplemented infrared spectroscopy with biochemical fractionation and proteomic profiling, which provide detailed information about blood serum composition. We built a model to describe serum absorption based on the concentrations of the highly-abundant proteins and applied this framework to lung cancer detection. We find that it is the levels of acute-phase proteins that change most in the presence of the disease and generate its infrared signature. These findings inform future clinical trials and establish a framework that could be applied to probing of any disease.

Published
2021

45. Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Author

Frank, Daria, Patnana, Pradeep Kumar, Vorwerk, Jan, Mao, Lianghao, Gopal, Lavanya Mokada, Jung, Noelle, Hennig, Thorben, Ruhnke, Leo, Frenz, Joris Maximillian, Kuppusamy, Maithreyan, Autry, Robert, Wei, Lanying, Sun, Kaiyan, Mohammed Ahmed, Helal Mohammed, Künstner, Axel, Busch, Hauke, Müller, Heiko, Hutter, Stephan, Hoermann, Gregor, Liu, Longlong, Xie, Xiaoqing, Al-Matary, Yahya, Nimmagadda, Subbaiah Chary, Cano, Fiorella Charles, Heuser, Michael, Thol, Felicitas, Göhring, Gudrun, Steinemann, Doris, Thomale, Jürgen, Leitner, Theo, Fischer, Anja, Rad, Roland, Röllig, Christoph, Altmann, Heidi, Kunadt, Desiree, Berdel, Wolfgang E., Hüve, Jana, Neumann, Felix, Klingauf, Jürgen, Calderon, Virginie, Opalka, Bertram, Dührsen, Ulrich, Rosenbauer, Frank, Dugas, Martin, Varghese, Julian, Reinhardt, Hans Christian, von Bubnoff, Nikolas, Möröy, Tarik, Lenz, Georg, Batcha, Aarif M. N., Giorgi, Marianna, Selvam, Murugan, Wang, Eunice, McWeeney, Shannon K., Tyner, Jeffrey W., Stölzel, Friedrich, Mann, Matthias, Jayavelu, Ashok Kumar, and Khandanpour, Cyrus

Published
2023
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46. Transcription Factor MAFF (MAF Basic Leucine Zipper Transcription Factor F) Regulates an Atherosclerosis Relevant Network Connecting Inflammation and Cholesterol Metabolism

Author

von Scheidt, Moritz, Zhao, Yuqi, de Aguiar Vallim, Thomas Q, Che, Nam, Wierer, Michael, Seldin, Marcus M, Franzén, Oscar, Kurt, Zeyneb, Pang, Shichao, Bongiovanni, Dario, Yamamoto, Masayuki, Edwards, Peter A, Ruusalepp, Arno, Kovacic, Jason C, Mann, Matthias, Björkegren, Johan LM, Lusis, Aldons J, Yang, Xia, and Schunkert, Heribert

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Health Sciences, Clinical Sciences, Sports Science and Exercise, Cardiovascular, Aging, Biotechnology, Heart Disease, Atherosclerosis, Heart Disease - Coronary Heart Disease, Human Genome, Genetics, Digestive Diseases, 2.1 Biological and endogenous factors, Animals, Cholesterol, DNA-Binding Proteins, Disease Models, Animal, Humans, Inflammation, MafF Transcription Factor, Male, Mice, Mice, Knockout, Nuclear Proteins, atherosclerosis, chromatin immunoprecipitation, coronary artery disease, inflammation, lipopolysaccharides, mafF transcription factor, receptors, LDL, receptors, LDL, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundCoronary artery disease (CAD) is a multifactorial condition with both genetic and exogenous causes. The contribution of tissue-specific functional networks to the development of atherosclerosis remains largely unclear. The aim of this study was to identify and characterize central regulators and networks leading to atherosclerosis.MethodsBased on several hundred genes known to affect atherosclerosis risk in mouse (as demonstrated in knockout models) and human (as shown by genome-wide association studies), liver gene regulatory networks were modeled. The hierarchical order and regulatory directions of genes within the network were based on Bayesian prediction models, as well as experimental studies including chromatin immunoprecipitation DNA-sequencing, chromatin immunoprecipitation mass spectrometry, overexpression, small interfering RNA knockdown in mouse and human liver cells, and knockout mouse experiments. Bioinformatics and correlation analyses were used to clarify associations between central genes and CAD phenotypes in both human and mouse.ResultsThe transcription factor MAFF (MAF basic leucine zipper transcription factor F) interacted as a key driver of a liver network with 3 human genes at CAD genome-wide association studies loci and 11 atherosclerotic murine genes. Most importantly, expression levels of the low-density lipoprotein receptor (LDLR) gene correlated with MAFF in 600 CAD patients undergoing bypass surgery (STARNET [Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task]) and a hybrid mouse diversity panel involving 105 different inbred mouse strains. Molecular mechanisms of MAFF were tested in noninflammatory conditions and showed positive correlation between MAFF and LDLR in vitro and in vivo. Interestingly, after lipopolysaccharide stimulation (inflammatory conditions), an inverse correlation between MAFF and LDLR in vitro and in vivo was observed. Chromatin immunoprecipitation mass spectrometry revealed that the human CAD genome-wide association studies candidate BACH1 (BTB domain and CNC homolog 1) assists MAFF in the presence of lipopolysaccharide stimulation with respective heterodimers binding at the MAF recognition element of the LDLR promoter to transcriptionally downregulate LDLR expression.ConclusionsThe transcription factor MAFF was identified as a novel central regulator of an atherosclerosis/CAD-relevant liver network. MAFF triggered context-specific expression of LDLR and other genes known to affect CAD risk. Our results suggest that MAFF is a missing link between inflammation, lipid and lipoprotein metabolism, and a possible treatment target.

Published
2021

48. In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance

Author

Wirth, Anna-Katharina, Wange, Lucas, Vosberg, Sebastian, Henrich, Kai-Oliver, Rausch, Christian, Özdemir, Erbey, Zeller, Christina M., Richter, Daniel, Feuchtinger, Tobias, Kaller, Markus, Hermeking, Heiko, Greif, Philipp A., Senft, Daniela, Jurinovic, Vindi, Bahrami, Ehsan, Jayavelu, Ashok Kumar, Westermann, Frank, Mann, Matthias, Enard, Wolfgang, Herold, Tobias, and Jeremias, Irmela

Published
2022
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