EkoEstMed

Developments in clinical-oriented decision support for high-throughput data in personalized medicine

About the project

Nowadays, precision medicine is becoming more and more of a reality and is moving further and further into clinical practice. Unique characteristics of The goal is to identify molecular features that may influence treatment recommendations and disease outcome as well as response to treatment. Therefore, we aim to estimate the likelihood of developing a particular type of cancer or the likelihood of recurrence and ultimately life expectancy.patients are identified to improve the efficacy and accuracy of their treatments. Ambitious initiatives such as the medical informatics initiative (MII) actively support biomedical research in Germany to improve individualized patient care. It relies heavily on the ever-growing amount of health-related data and constantly evolving technologies. However, due to a lack of analytical methods and standardization and harmonization processes, only part of the existing data is used for clinical recommendations. Thus, the goal is to prepare and present the complex data in an understandable form through the development of innovative methods, such as machine learning (artificial intelligence) algorithms, and analysis processes, while making them available for exchange in an efficient and usable manner. In addition, efficient IT infrastructures as well as the development of novel visualization standards will be created to ensure implementation and application in the clinic. This project will not only advance the processes of personalized medicine in the local clinical setting, but also MII and MIRACUM at various sites.

Goals

1. Methods for the development, provision and use of omics data

The goal is to develop standardization methods to properly store, annotate, and share the omics/high-throughput data being generated, while also developing visualization methods for preparing and using this high-dimensional data for clinical applications.

2. Integration of multi-omics data

The integration of omics data, which on the one hand originate from different clinical laboratories, and on the other hand can be used from public databases, are usually accompanied by possible batch effects. For this purpose, appropriate methods and approaches of batch effect correction will be developed and applied. At the same time, other co-factors such as gender, age, and environment will be taken into account. In addition, correlation and interaction analyses of the different omics data sets will be applied and further developed, which will finally lead to a score for the assessment of pathogenicity.

3. Development of decision support tools in the clinical context

The goal is to identify molecular features that may influence treatment recommendations and disease outcome as well as response to treatment. Therefore, we aim to estimate the likelihood of developing a particular type of cancer or the likelihood of recurrence and ultimately life expectancy.

Lead of the Junior Research Group

Dr. Geoffroy Andrieux

Lead of the Junior Research Group EkoEstMed
Institute for Medical Bioinformatics and System Medicine | Albert-Ludwigs-Universität Freiburg

Contakt

Publications

Journal Publication

Czech, M, Schneider, S, Peltokangas, N, El Khawanky, N, Ghimire, S, Andrieux, G, nker, J, Krausz, M, Proietti, M, Braun, LM, ckert, T, Langenbach, M, Schmidt, D, Martin, I, Wenger, V, de Vega, E, Haring, E, Pourjam, M, Pfeifer, D, Schmitt-Graeff, A, Grimbacher, B, Aumann, K, Kircher, B, Tilg, H, Raffatellu, M, Thiele Orberg, E, cker, G, Duyster, J, hler, N, Holler, E, Nachbaur, D, Boerries, M, Gerner, RR, n, D, Zeiser, R (2024). Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease. Sci Transl Med, 16, 735:eadi1501.
Weinelt, N, Wächtershäuser, KN, Celik, G, Jeiler, B, Gollin, I, Zein, L, Smith, S, Andrieux, G, Das, T, Roedig, J, Feist, L, Rotter, B, Boerries, M, Pampaloni, F, van Wijk, SJL (2024). LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL. Cell Death Dis, 15, 1:77.
Staniek, J, Kalina, T, Andrieux, G, Boerries, M, Janowska, I, Fuentes, M, ez, P, Bakardjieva, M, Stancikova, J, Raabe, J, Neumann, J, Schwenk, S, Arpesella, L, Stuchly, J, Benes, V, a Valiente, R, a, J, Carsetti, R, Piano Mortari, E, Catala, A, de la Calle, O, Sogkas, G, Neven, B, Rieux-Laucat, F, Magerus, A, Neth, O, Olbrich, P, Voll, RE, Alsina, L, Allende, LM, Gonzalez-Granado, LI, hler, C, Thiel, J, Venhoff, N, Lorenzetti, R, Warnatz, K, Unger, S, Seidl, M, Mielenz, D, Schneider, P, Ehl, S, Rensing-Ehl, A, Smulski, CR, Rizzi, M (2024). Non-apoptotic FAS signaling controls mTOR activation and extrafollicular maturation in human B cells. Sci Immunol, 9, 91:eadj5948.
Maas-Bauer, K, Stell, AV, Yan, KL, de Vega, E, Vinnakota, JM, Unger, S, ez, N, Norona, J, Talvard-Balland, N, mann, S, Schwan, C, Miething, C, Martens, US, Shoumariyeh, K, Nestor, RP, Duquesne, S, Hanke, K, Rackiewicz, M, Hu, Z, El Khawanky, N, Taromi, S, Andrlova, H, Faraidun, H, Walter, S, Pfeifer, D, Follo, M, Waldschmidt, J, Melchinger, W, Rassner, M, Wehr, C, Schmitt-Graeff, A, Halbach, S, Liao, J, cker, G, Brummer, T, Dengjel, J, Andrieux, G, Grosse, R, Tugues, S, Blazar, BR, Becher, B, Boerries, M, Zeiser, R (2024). ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease. Nat Commun, 15, 1:446.
Torella, L, Klermund, J, Bilbao-Arribas, M, Tamayo, I, Andrieux, G, Chmielewski, KO, Vales, A, e, C, Moreno-Luqui, D, Raimondi, I, Abad, A, Torrens-Baile, J, Salido, E, Huarte, M, Hernaez, M, Boerries, M, Cathomen, T, Zabaleta, N, Gonzalez-Aseguinolaza, G (2024). Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1. EMBO Mol Med, 16, 1:112-131.
Wu, Y, Zehnle, PMA, Rajak, J, Koleci, N, Andrieux, G, Gallego-Villar, L, Aumann, K, Boerries, M, Niemeyer, CM, Flotho, C, Bohler, S, Erlacher, M (2024). BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia. Leukemia, 38, 1:136-148.
Ramamoorthy, S, Lebrecht, D, Schanze, D, Schanze, I, Wieland, I, Andrieux, G, Metzger, P, Hess, M, Albert, MH, Borkhardt, A, Bresters, D, Buechner, J, Catala, A, De Haas, V, Dworzak, M, Erlacher, M, Hasle, H, Jahnukainen, K, Locatelli, F, Masetti, R, Stary, J, Turkiewicz, D, Vinci, L, Wlodarski, MW, Yoshimi, A, Boerries, M, Niemeyer, CM, Zenker, M, Flotho, C (2024). Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup. Br J Haematol, 204, 2:595-605.
Dettmer-Monaco, V, Weißert, K, Ammann, S, Monaco, G, Lei, L, Gräßel, L, Rhiel, M, Rositzka, J, Kaufmann, MM, Geiger, K, Andrieux, G, Lao, J, Thoulass, G, Schell, C, Boerries, M, Illert, AL, Cornu, TI, Ehl, S, Aichele, P, Cathomen, T (2024). Gene editing of hematopoietic stem cells restores T-cell response in familial hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol, 153, 1:243-255.e14.
Dibas, A, Rhiel, M, Patel, VB, Andrieux, G, Boerries, M, Cornu, TI, Alzubi, J, Cathomen, T (2023). Cell-Based Models of ‘Cytokine Release Syndrome’ Endorse CD40L and Granulocyte-Macrophage Colony-Stimulating Factor Knockout in Chimeric Antigen Receptor T Cells as Mitigation Strategy. Cells, 12, 21:no page given.
Cardenas, RM, Brandl, SM, ndez, AV, Schlaak, AE, Buschky, A, Peters, T, Beier, F, Serrels, B, Taromi, S, Raute, K, Hauri, S, Gstaiger, M, Lassmann, S, Huppa, JB, Boerries, M, Andrieux, G, Bengsch, B, Schamel, WW, Minguet, S (2023). Harnessing CD3 diversity to optimize CAR T cells. Nat Immunol, 24, 12:2135-2149.
Marone, R, Landmann, E, Devaux, A, Lepore, R, Seyres, D, Zuin, J, Burgold, T, Engdahl, C, Capoferri, G, Dell’Aglio, A, Larrue, C, Simonetta, F, Rositzka, J, Rhiel, M, Andrieux, G, Gallagher, DN, der, MS, Wiederkehr, A, Sinopoli, A, Do Sacramento, V, Haydn, A, Garcia-Prat, L, Divsalar, C, Camus, A, Xu, L, Bordoli, L, Schwede, T, Porteus, M, Tamburini, J, Corn, JE, Cathomen, T, Cornu, TI, Urlinger, S, Jeker, LT (2023). Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy. J Exp Med, 220, 12:no page given.
Apostolova, P, Kreutmair, S, Toffalori, C, Punta, M, Unger, S, Burk, AC, Wehr, C, Maas-Bauer, K, Melchinger, W, Haring, E, Hoefflin, R, Shoumariyeh, K, Hupfer, V, Lauer, EM, Duquesne, S, Lowinus, T, ez, N, Alberti, C, da Costa Pereira, S, Merten, CH, Power, L, Weiss, M, ke, C, Pfeifer, D, Marks, R, Bertz, H, sch, R, Ihorst, G, Gentner, B, Duyster, J, Boerries, M, Andrieux, G, Finke, J, Becher, B, Vago, L, Zeiser, R (2023). Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-Immune signature correlates with response. Br J Haematol, 203, 2:264-281.
Metzger, P, Hess, ME, Blaumeiser, A, Pauli, T, Schipperges, V, Mertes, R, Christoph, J, Unberath, P, Reimer, N, Scheible, R, Illert, AL, Busch, H, Andrieux, G, Boerries, M (2023). MIRACUM-Pipe: An Adaptable Pipeline for Next-Generation Sequencing Analysis, Reporting, and Visualization for Clinical Decision Making. Cancers (Basel), 15, 13:no page given.
Andrieux, G, Das, T, Griffin, M, Straehle, J, Paine, SML, Beck, J, Boerries, M, Heiland, DH, Smith, SJ, Rahman, R, Chakraborty, S (2023). Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence. Genome Med, 15, 1:48.
Lenz, M, Eichler, A, Kruse, P, Galanis, C, Kleidonas, D, Andrieux, G, Boerries, M, Jedlicka, P, ller, U, Deller, T, Vlachos, A (2023). The Amyloid Precursor Protein Regulates Synaptic Transmission at Medial Perforant Path Synapses. J Neurosci, 43, 29:5290-5304.
Kleidonas, D, Kirsch, M, Andrieux, G, Pfeifer, D, Boerries, M, Vlachos, A (2023). Microglia modulate TNFa-mediated synaptic plasticity. Glia, 71, 9:2117-2136.
Raute, K, Strietz, J, Parigiani, MA, Andrieux, G, Thomas, OS, Kistner, KM, Zintchenko, M, Aichele, P, Hofmann, M, Zhou, H, Weber, W, Boerries, M, Swamy, M, Maurer, J, Minguet, S (2023). T-cell Ligands. Cancer Immunol Res, :OF1-OF20.
Langenbach, M, Giesler, S, Richtsfeld, S, da Costa-Pereira, S, Rindlisbacher, L, Wertheimer, T, Braun, LM, Andrieux, G, Duquesne, S, Pfeifer, D, Woessner, NM, Menssen, HD, Taromi, S, Duyster, J, Boerries, M, Brummer, T, Blazar, BR, Minguet, S, Turko, P, Levesque, MP, Becher, B, Zeiser, R (2023). MDM2 inhibition enhances immune checkpoint inhibitor efficacy by increasing IL-15 and MHC class II production. Mol Cancer Res, :no page given.
Carusillo, A, Haider, S, fer, R, Rhiel, M, rk, D, Chmielewski, KO, Klermund, J, Mosti, L, Andrieux, G, fer, R, Cornu, TI, Cathomen, T, Mussolino, C (2023). A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells. Nucleic Acids Res, :no page given.
Greve, G, Andrieux, G, Schlosser, P, Blagitko-Dorfs, N, Rehman, UU, Ma, T, Pfeifer, D, Heil, G, Neubauer, A, Krauter, J, Heuser, M, Salih, HR, hner, K, hner, H, Hackanson, B, Boerries, M, bbert, M (2023). In vivo kinetics of early, non-random methylome and transcriptome changes induced by DNA-hypomethylating treatment in primary AML blasts. Leukemia, :no page given.
Rhiel, M, Geiger, K, Andrieux, G, Rositzka, J, Boerries, M, Cathomen, T, Cornu, TI (2023). T-CAST: An optimized CAST-Seq pipeline for TALEN confirms superior safety and efficacy of obligate-heterodimeric scaffolds. Front Genome Ed, 5:1130736.
Paul, MC, Schneeweis, C, à, C, Shan, C, Rossmeisl, D, Koutsouli, S, Klement, C, Zukowska, M, Widholz, SA, Jesinghaus, M, Heuermann, KK, Engleitner, T, Seidler, B, Sleiman, K, Steiger, K, Tschurtschenthaler, M, Walter, B, Weidemann, SA, Pietsch, R, Schnieke, A, Schmid, RM, Robles, MS, Andrieux, G, Boerries, M, Rad, R, Schneider, G, Saur, D (2023). Non-canonical functions of SNAIL drive context-specific cancer progression. Nat Commun, 14, 1:1201.
Isbell, LK, Tschuch, C, Doostkam, S, Waldeck, S, Andrieux, G, Shoumariyeh, K, Lenhard, D, Schaefer, HE, Reinacher, PC, Bartsch, I, Pantic, M, Vinnakota, JM, Kakkassery, V, Schorb, E, Scherer, F, Frey, AV, Boerries, M, Illerhaus, G, Duyster, J, Schueler, J, von Bubnoff, N (2023). Patient-derived xenograft mouse models to investigate tropism to the central nervous system and retina of primary and secondary central nervous system lymphoma. Neuropathol Appl Neurobiol, 49, 2:e12899.
Ruckert, T, Andrieux, G, Boerries, M, ller, K, Woessner, NM, Doetsch, S, Schell, C, Aumann, K, Kolter, J, Schmitt-Graeff, A, Schiff, M, Braun, LM, Haring, E, Kissel, S, Siranosian, BA, Bhatt, AS, Nordkild, P, Wehkamp, J, Jensen, BAH, Minguet, S, Duyster, J, Zeiser, R, hler, N (2022). Human Beta-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling. Sci Transl Med, 14, 676:eabp9675.
Ferrarese, R, Izzo, A, Andrieux, G, Lagies, S, Bartmuss, JP, Masilamani, AP, Wasilenko, A, Osti, D, Faletti, S, Schulzki, R, Yuan, S, Kling, E, Ribecco, V, Heiland, DH, Tholen, S, Prinz, M, Pelicci, G, Kammerer, B, Boerries, M, Carro, MS (2023). ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastoma. Life Sci Alliance, 6, 1:no page given.
Strohmeier, V, Andrieux, G, Unger, S, Pascual-Reguant, A, Klocperk, A, Seidl, M, Marques, OC, Eckert, M, we, K, Shabani, M, von Spee-Mayer, C, Friedmann, D, Harder, I, Gutenberger, S, Keller, B, Proietti, M, Bulashevska, A, Grimbacher, B, Provaznik, J, Benes, V, Goldacker, S, Schell, C, Hauser, AE, Boerries, M, Hasselblatt, P, Warnatz, K (2023). Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection. J Clin Immunol, 43, 2:371-390.
Chakraborty, S, Andrieux, G, Kastl, P, Adlung, L, Altamura, S, Boehm, ME, ller, LE, Abdullah, Y, Wagner, MC, Helm, B, ne, HJ, Lehmann, WD, Boerries, M, Busch, H, Muckenthaler, MU, Schilling, M, ller, U (2022). Erythropoietin-driven dynamic proteome adaptations during erythropoiesis prevent iron overload in the developing embryo. Cell Rep, 40, 12:111360.
Aktories, P, Petry, P, Glatz, P, Andrieux, G, Oschwald, A, Botterer, H, Gorka, O, Erny, D, Boerries, M, Henneke, P, ß, O, Prinz, M, Kierdorf, K (2022). . Cell Rep Methods, 2, 8:100260.
Karlowitz, R, Stanifer, ML, Roedig, J, Andrieux, G, Bojkova, D, Bechtel, M, Smith, S, Kowald, L, Schubert, R, Boerries, M, Cinatl, J, Boulant, S, van Wijk, SJL (2022). USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING. Cell Death Dis, 13, 8:684.
Wanner, N, Andrieux, G, Badia-I-Mompel, P, Edler, C, Pfefferle, S, Lindenmeyer, MT, Schmidt-Lauber, C, Czogalla, J, Wong, MN, Okabayashi, Y, Braun, F, tgehetmann, M, Meister, E, Lu, S, Noriega, MLM, nther, T, Grundhoff, A, Fischer, N, uninger, H, Lindner, D, Westermann, D, Haas, F, Roedl, K, Kluge, S, Addo, MM, Huber, S, Lohse, AW, Reiser, J, Ondruschka, B, Sperhake, JP, Saez-Rodriguez, J, Boerries, M, Hayek, SS, Aepfelbacher, M, Scaturro, P, Puelles, VG, Huber, TB (2022). Molecular consequences of SARS-CoV-2 liver tropism. Nat Metab, 4, 3:310-319.