442 results on '"Alawi, Malik"'
Search Results
2. Biallelic FRA10AC1 variants cause a neurodevelopmental disorder with growth retardation.
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von Elsner, Leonie, Chai, Guoliang, Schneeberger, Pauline E, Harms, Frederike L, Casar, Christian, Qi, Minyue, Alawi, Malik, Abdel-Salam, Ghada MH, Zaki, Maha S, Arndt, Florian, Yang, Xiaoxu, Stanley, Valentina, Hempel, Maja, Gleeson, Joseph G, and Kutsche, Kerstin
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Brain Disorders ,Neurosciences ,Clinical Research ,Intellectual and Developmental Disabilities (IDD) ,Rare Diseases ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,DNA-Binding Proteins ,Growth Disorders ,Humans ,Intellectual Disability ,Membrane Proteins ,Microcephaly ,Neurodevelopmental Disorders ,Nuclear Proteins ,RNA Splice Sites ,RNA-Binding Proteins ,Repressor Proteins ,exome sequencing ,homozygous ,major spliceosome ,splicing ,intellectual disability ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery - Abstract
The major spliceosome mediates pre-mRNA splicing by recognizing the highly conserved sequences at the 5' and 3' splice sites and the branch point. More than 150 proteins participate in the splicing process and are organized in the spliceosomal A, B, and C complexes. FRA10AC1 is a peripheral protein of the spliceosomal C complex and its ortholog in the green alga facilitates recognition or interaction with splice sites. We identified biallelic pathogenic variants in FRA10AC1 in five individuals from three consanguineous families. The two unrelated Patients 1 and 2 with loss-of-function variants showed developmental delay, intellectual disability, and no speech, while three siblings with the c.494_496delAAG (p.Glu165del) variant had borderline to mild intellectual disability. All patients had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism. FRA10AC1 transcripts and proteins were drastically reduced or absent in fibroblasts of Patients 1 and 2. In a heterologous expression system, the p.Glu165del variant impacts intrinsic stability of FRA10AC1 but does not affect its nuclear localization. By co-immunoprecipitation, we found ectopically expressed HA-FRA10AC1 in complex with endogenous DGCR14, another component of the spliceosomal C complex, while the splice factors CHERP, NKAP, RED, and SF3B2 could not be co-immunoprecipitated. Using an in vitro splicing reporter assay, we did not obtain evidence for FRA10AC1 deficiency to suppress missplicing events caused by mutations in the highly conserved dinucleotides of 5' and 3' splice sites in an in vitro splicing assay in patient-derived fibroblasts. Our data highlight the importance of specific peripheral spliceosomal C complex proteins for neurodevelopment. It remains possible that FRA10AC1 may have other and/or additional cellular functions, such as coupling of transcription and splicing reactions.
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- 2022
3. A deep intronic variant in DNM1 in a patient with developmental and epileptic encephalopathy creates a splice acceptor site and affects only transcript variants including exon 10a
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Harms, Frederike L., Weiss, Deike, Lisfeld, Jasmin, Alawi, Malik, and Kutsche, Kerstin
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- 2023
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4. INPP4A-related genetic and phenotypic spectrum and functional relevance of subcellular targeting of INPP4A isoforms
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Hecher, Laura, Harms, Frederike L., Lisfeld, Jasmin, Alawi, Malik, Denecke, Jonas, and Kutsche, Kerstin
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- 2023
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5. Hypoimmune induced pluripotent stem cell–derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice
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Deuse, Tobias, Tediashvili, Grigol, Hu, Xiaomeng, Gravina, Alessia, Tamenang, Annika, Wang, Dong, Connolly, Andrew, Mueller, Christian, Mallavia, Beñat, Looney, Mark R, Alawi, Malik, Lanier, Lewis L, and Schrepfer, Sonja
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Stem Cell Research - Embryonic - Non-Human ,Cardiovascular ,Regenerative Medicine ,Transplantation ,Heart Disease ,Biotechnology ,Lung ,Stem Cell Research ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,Animals ,Cardiovascular Diseases ,Endothelial Cells ,Heart Failure ,Hindlimb ,Immunocompetence ,Induced Pluripotent Stem Cells ,Ischemia ,Lung Diseases ,Mice ,Inbred BALB C ,Mice ,Inbred C57BL ,Myocytes ,Cardiac ,Stem Cell Transplantation ,Transplantation ,Homologous ,alpha 1-Antitrypsin ,hypoimmune stem cells ,immune evasion ,cell therapy - Abstract
The emerging field of regenerative cell therapy is still limited by the few cell types that can reliably be differentiated from pluripotent stem cells and by the immune hurdle of commercially scalable allogeneic cell therapeutics. Here, we show that gene-edited, immune-evasive cell grafts can survive and successfully treat diseases in immunocompetent, fully allogeneic recipients. Transplanted endothelial cells improved perfusion and increased the likelihood of limb preservation in mice with critical limb ischemia. Endothelial cell grafts transduced to express a transgene for alpha1-antitrypsin (A1AT) successfully restored physiologic A1AT serum levels in mice with genetic A1AT deficiency. This cell therapy prevented both structural and functional changes of emphysematous lung disease. A mixture of endothelial cells and cardiomyocytes was injected into infarcted mouse hearts, and both cell types orthotopically engrafted in the ischemic areas. Cell therapy led to an improvement in invasive hemodynamic heart failure parameters. Our study supports the development of hypoimmune, universal regenerative cell therapeutics for cost-effective treatments of major diseases.
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- 2021
6. The SIRPα–CD47 immune checkpoint in NK cells
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Deuse, Tobias, Hu, Xiaomeng, Agbor-Enoh, Sean, Jang, Moon K, Alawi, Malik, Saygi, Ceren, Gravina, Alessia, Tediashvili, Grigol, Nguyen, Vinh Q, Liu, Yuan, Valantine, Hannah, Lanier, Lewis L, and Schrepfer, Sonja
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Cancer ,Vaccine Related ,Prevention ,Immunization ,HIV/AIDS ,Vaccine Related (AIDS) ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,CD47 Antigen ,Cells ,Cultured ,Cytokines ,Cytotoxicity ,Immunologic ,Endothelial Cells ,Histocompatibility Antigens Class I ,Humans ,Immune Checkpoint Inhibitors ,Killer Cells ,Natural ,Macaca mulatta ,Macrophages ,Mice ,Inbred BALB C ,Mice ,Inbred C57BL ,Protein Binding ,Receptors ,Immunologic ,Species Specificity ,Medical and Health Sciences ,Immunology - Abstract
Here we report on the existence and functionality of the immune checkpoint signal regulatory protein α (SIRPα) in NK cells and describe how it can be modulated for cell therapy. NK cell SIRPα is up-regulated upon IL-2 stimulation, interacts with target cell CD47 in a threshold-dependent manner, and counters other stimulatory signals, including IL-2, CD16, or NKG2D. Elevated expression of CD47 protected K562 tumor cells and mouse and human MHC class I-deficient target cells against SIRPα+ primary NK cells, but not against SIRPα- NKL or NK92 cells. SIRPα deficiency or antibody blockade increased the killing capacity of NK cells. Overexpression of rhesus monkey CD47 in human MHC-deficient cells prevented cytotoxicity by rhesus NK cells in a xenogeneic setting. The SIRPα-CD47 axis was found to be highly species specific. Together, the results demonstrate that disruption of the SIRPα-CD47 immune checkpoint may augment NK cell antitumor responses and that elevated expression of CD47 may prevent NK cell-mediated killing of allogeneic and xenogeneic tissues.
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- 2021
7. Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 in two new patients with the same homozygous TMCO1 variant and review of the literature
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Abdelrazek, Ibrahim M., Holling, Tess, Harms, Frederike L., Alawi, Malik, Omar, Tarek, Abdalla, Ebtesam, and Kutsche, Kerstin
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- 2023
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8. Characterization of IG-MYC-breakpoints and their application for quantitative minimal disease monitoring in high-risk pediatric Burkitt-lymphoma and -leukemia
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Möker, Paula, zur Stadt, Udo, Zimmermann, Martin, Alawi, Malik, Mueller, Stephanie, Finger, Jasmin, Knörr, Fabian, Riquelme, Amambay, Oschlies, Ilske, Klapper, Wolfram, Bradtke, Jutta, Burkhardt, Birgit, Woessmann, Wilhelm, and Damm-Welk, Christine
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- 2022
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9. Novel biallelic variants expand the SLC5A6-related phenotypic spectrum
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Holling, Tess, Nampoothiri, Sheela, Tarhan, Bedirhan, Schneeberger, Pauline E., Vinayan, Kollencheri Puthenveettil, Yesodharan, Dhanya, Roy, Arun Grace, Radhakrishnan, Periyasamy, Alawi, Malik, Rhodes, Lindsay, Girisha, Katta Mohan, Kang, Peter B., and Kutsche, Kerstin
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- 2022
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10. Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice
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Schepanski, Steven, Chini, Mattia, Sternemann, Veronika, Urbschat, Christopher, Thiele, Kristin, Sun, Ting, Zhao, Yu, Poburski, Mareike, Woestemeier, Anna, Thieme, Marie-Theres, Zazara, Dimitra E., Alawi, Malik, Fischer, Nicole, Heeren, Joerg, Vladimirov, Nikita, Woehler, Andrew, Puelles, Victor G., Bonn, Stefan, Gagliani, Nicola, Hanganu-Opatz, Ileana L., and Arck, Petra C.
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- 2022
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11. Intestinal Epithelia and Myeloid Immune Cells Shape Colitis Severity and Colorectal Carcinogenesis via High-mobility Group Box Protein 1.
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Foelsch, Katharina, Pelczar, Penelope, Zierz, Elisabeth, Kondratowicz, Stephanie, Qi, Minyue, Mueller, Christian, Alawi, Malik, Huebener, Sina, Clauditz, Till, Gagliani, Nicola, Huber, Samuel, and Huebener, Peter
- Abstract
Background High-mobility group box protein 1 [HMGB1] is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and in infectious inflammation. Stool and serum HMGB1 levels correlate with colitis severity and colorectal cancer [CRC] progression, yet recent reports indicate that HMGB1 mainly operates as an intracellular determinant of enterocyte fate during colitis, and investigations into the roles of HMGB1 in CRC are lacking. Methods Using mice with conditional HMGB1-knockout in enterocytes [ Hmgb1
ΔIEC ] and myeloid cells [ Hmgb1ΔLysM ], respectively, we explored functions of HMGB1 in pathogenetically diverse contexts of colitis and colitis-associated CRC. Results HMGB1 is overexpressed in human inflammatory bowel disease and gastrointestinal cancers, and HMGB1 protein localises in enterocytes and stromal cells in colitis and CRC specimens from humans and rodents. As previously described, enterocyte HMGB1 deficiency aggravates severe chemical-induced intestinal injury, but not Citrobacter rodentium or T cell transfer colitis in mice. HMGB1 - deficient enterocytes and organoids do not exhibit deviant apoptotic or autophagic activity, altered proliferative or migratory capacity, abnormal intestinal permeability, or aberrant DSS-induced organoid inflammation in vitro. Instead, we observed altered in vivo reprogramming of both intestinal epithelia and infiltrating myeloid cells in Hmgb1ΔIEC early during colitis, suggesting HMGB1-mediated paracrine injury signalling. Hmgb1ΔIEC had higher CRC burden than wild types in the Apc+/min model, whereas inflammatory CRC was attenuated in Hmgb1ΔLysM . Cellular and molecular phenotyping of Hmgb1ΔIEC and Hmgb1ΔLysM cancers indicates context-dependent transcriptional modulation of immune signalling and extracellular matrix remodelling via HMGB1. Conclusion Enterocytes and myeloid cells context-dependently regulate host responses to severe colitis and maladaptive intestinal wound healing via HMGB1. [ABSTRACT FROM AUTHOR]- Published
- 2024
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12. Author Correction: The landscape of viral associations in human cancers
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Zapatka, Marc, Borozan, Ivan, Brewer, Daniel S., Iskar, Murat, Grundhoff, Adam, Alawi, Malik, Desai, Nikita, Sültmann, Holger, Moch, Holger, Cooper, Colin S., Eils, Roland, Ferretti, Vincent, and Lichter, Peter
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- 2023
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13. Multiplexed mRNA analysis of brain-derived extracellular vesicles upon experimental stroke in mice reveals increased mRNA content with potential relevance to inflammation and recovery processes
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Bub, Annika, Brenna, Santra, Alawi, Malik, Kügler, Paul, Gui, Yuqi, Kretz, Oliver, Altmeppen, Hermann, Magnus, Tim, and Puig, Berta
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- 2022
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14. Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism
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Harms, Frederike Leonie, Girisha, Katta M, Hardigan, Andrew A, Kortüm, Fanny, Shukla, Anju, Alawi, Malik, Dalal, Ashwin, Brady, Lauren, Tarnopolsky, Mark, Bird, Lynne M, Ceulemans, Sophia, Bebin, Martina, Bowling, Kevin M, Hiatt, Susan M, Lose, Edward J, Primiano, Michelle, Chung, Wendy K, Juusola, Jane, Akdemir, Zeynep C, Bainbridge, Matthew, Charng, Wu-Lin, Drummond-Borg, Margaret, Eldomery, Mohammad K, El-Hattab, Ayman W, Saleh, Mohammed AM, Bézieau, Stéphane, Cogné, Benjamin, Isidor, Bertrand, Küry, Sébastien, Lupski, James R, Myers, Richard M, Cooper, Gregory M, and Kutsche, Kerstin
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Biotechnology ,Brain Disorders ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,2.1 Biological and endogenous factors ,Aetiology ,Generic health relevance ,Adolescent ,Adult ,Amino Acid Substitution ,Ataxia ,Child ,Child ,Preschool ,Chromatin ,Cyclin-Dependent Kinase Inhibitor p21 ,Developmental Disabilities ,Exome ,Face ,Female ,Gene Expression Regulation ,Genes ,Reporter ,HEK293 Cells ,Humans ,Intellectual Disability ,Language Development Disorders ,Male ,Models ,Molecular ,Mosaicism ,Mutation ,Neurodevelopmental Disorders ,Protein Transport ,Syndrome ,Transcription Factors ,Transcription ,Genetic ,EBF3 ,de novo mutation ,developmental delay ,gene regulation ,intellectual disability ,transcription factor ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
From a GeneMatcher-enabled international collaboration, we identified ten individuals affected by intellectual disability, speech delay, ataxia, and facial dysmorphism and carrying a deleterious EBF3 variant detected by whole-exome sequencing. One 9-bp duplication and one splice-site, five missense, and two nonsense variants in EBF3 were found; the mutations occurred de novo in eight individuals, and the missense variant c.625C>T (p.Arg209Trp) was inherited by two affected siblings from their healthy mother, who is mosaic. EBF3 belongs to the early B cell factor family (also known as Olf, COE, or O/E) and is a transcription factor involved in neuronal differentiation and maturation. Structural assessment predicted that the five amino acid substitutions have damaging effects on DNA binding of EBF3. Transient expression of EBF3 mutant proteins in HEK293T cells revealed mislocalization of all but one mutant in the cytoplasm, as well as nuclear localization. By transactivation assays, all EBF3 mutants showed significantly reduced or no ability to activate transcription of the reporter gene CDKN1A, and in situ subcellular fractionation experiments demonstrated that EBF3 mutant proteins were less tightly associated with chromatin. Finally, in RNA-seq and ChIP-seq experiments, EBF3 acted as a transcriptional regulator, and mutant EBF3 had reduced genome-wide DNA binding and gene-regulatory activity. Our findings demonstrate that variants disrupting EBF3-mediated transcriptional regulation cause intellectual disability and developmental delay and are present in ∼0.1% of individuals with unexplained neurodevelopmental disorders.
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- 2017
15. Genomic characterization of vulvar squamous cell carcinoma
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Prieske, Katharina, Alawi, Malik, Oliveira-Ferrer, Leticia, Jaeger, Anna, Eylmann, Kathrin, Burandt, Eike, Schmalfeldt, Barbara, Joosse, Simon A., and Woelber, Linn
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- 2020
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16. A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice
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Zazara, Dimitra E., Wegmann, Michael, Giannou, Anastasios D., Hierweger, Alexandra Maximiliane, Alawi, Malik, Thiele, Kristin, Huber, Samuel, Pincus, Maike, Muntau, Ania C., Solano, Maria Emilia, and Arck, Petra C.
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- 2020
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17. Glioma escape signature and clonal development under immune pressure
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Maire, Cecile L., Mohme, Malte, Bockmayr, Michael, Fita, Krystian D., Riecken, Kristoffer, Bornigen, Daniela, Alawi, Malik, Failla, Antonio, Kolbe, Katharina, Zapf, Svenja, Holz, Mareike, Neumann, Katrin, Duhrsen, Lasse, Lange, Tobias, Fehse, Boris, Westphal, Manfred, and Lamszus, Katrin
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Gliomas -- Genetic aspects ,B cells -- Genetic aspects ,Genes -- Genetic aspects ,Immunotherapy ,Palladium ,Health care industry - Abstract
Immunotherapeutic strategies are increasingly important in neuro-oncology, and the elucidation of escape mechanisms that lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing WT and [Pd-1.sup.-/-] mice survived significantly longer than immunodeficient [Pfp.sup.-/-] [Rag2.sup.-/-] mice. While tumors in [Pfp.sup.-/-] [Rag2.sup.-/-] mice were highly polyclonal, immunoedited tumors in WT and [Pd-1.sup.-/-] mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in WT mice were distinguished by an IFN-[gamma]-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even more strongly to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas., Introduction Glioblastoma represents the most frequent aggressive intrinsic brain tumor, and patient outcome remains uniformly fatal despite improved treatment options (1). The current era of glioblastoma therapy is being redefined [...]
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- 2020
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18. Impact of Multiple Minor Histocompatibility Antigen Differences on Graft-Versus-Host Disease and Relapse Risk in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients
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Mueller, Christian, primary, Alawi, Malik, additional, Loeffler, Juergen, additional, Bonin, Michael, additional, Schreiber, Andreas, additional, Kreyenberg, Hermann, additional, Wiegering, Verena, additional, Woelfl, Matthias, additional, Caruana, Ignazio, additional, Schlegel, Paul G., additional, and Eyrich, Matthias, additional
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- 2023
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19. Complete genome sequence of a Staphylococcus condimenti isolated from a port catheter-associated bloodstream infection
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Berneking, Laura, primary, Büttner, Henning, additional, Qi, Minyue, additional, Günther, Thomas, additional, Lehnhoff, Daniel, additional, Both, Anna, additional, Christner, Martin, additional, Wolters, Manuel, additional, Alawi, Malik, additional, Aepfelbacher, Martin, additional, and Rohde, Holger, additional
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- 2023
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20. Stenotrophomonas maltophilia affects the gene expression profiles of the major pathogens Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro multispecies biofilm model
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Alio, Ifey, primary, Moll, Raphael, additional, Hoffmann, Tim, additional, Mamat, Uwe, additional, Schaible, Ulrich E., additional, Pappenfort, Kai, additional, Alawi, Malik, additional, Schie, Marcel, additional, Thünauer, Roland, additional, Stamm, Johanna, additional, Rohde, Holger, additional, and Streit, Wolfgang R., additional
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- 2023
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21. Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer
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Voß, Hannah, Wurlitzer, Marcus, Smit, Daniel J., Ewald, Florian, Alawi, Malik, Spohn, Michael, Indenbirken, Daniela, Omidi, Maryam, David, Kerstin, Juhl, Hartmut, Simon, Ronald, Sauter, Guido, Fischer, Lutz, Izbicki, Jakob R., Molloy, Mark P., Nashan, Björn, Schlüter, Hartmut, and Jücker, Manfred
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- 2020
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22. Vertically transferred maternal immune cells promote neonatal immunity against early life infections
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Stelzer, Ina Annelies, Urbschat, Christopher, Schepanski, Steven, Thiele, Kristin, Triviai, Ioanna, Wieczorek, Agnes, Alawi, Malik, Ohnezeit, Denise, Kottlau, Julian, Huang, Jiabin, Fischer, Nicole, Mittrücker, Hans-Willi, Solano, Maria Emilia, Fehse, Boris, Diemert, Anke, Stahl, Felix R., and Arck, Petra Clara
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- 2021
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23. The landscape of viral associations in human cancers
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Zapatka, Marc, Borozan, Ivan, Brewer, Daniel S., Iskar, Murat, Grundhoff, Adam, Alawi, Malik, Desai, Nikita, Sültmann, Holger, Moch, Holger, Cooper, Colin S., Eils, Roland, Ferretti, Vincent, and Lichter, Peter
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- 2020
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24. Extremophilic nitrite-oxidizing Chloroflexi from Yellowstone hot springs
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Spieck, Eva, Spohn, Michael, Wendt, Katja, Bock, Eberhard, Shively, Jessup, Frank, Jeroen, Indenbirken, Daniela, Alawi, Malik, Lücker, Sebastian, and Hüpeden, Jennifer
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- 2020
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25. De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans
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Deuse, Tobias, Hu, Xiaomeng, Agbor-Enoh, Sean, Koch, Martina, Spitzer, Matthew H., Gravina, Alessia, Alawi, Malik, Marishta, Argit, Peters, Bjoern, Kosaloglu-Yalcin, Zeynep, Yang, Yanqin, Rajalingam, Raja, Wang, Dong, Nashan, Bjoern, Kiefmann, Rainer, Reichenspurner, Hermann, Valantine, Hannah, Weissman, Irving L., and Schrepfer, Sonja
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- 2019
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26. Classification of Brain Tumors by Nanopore Sequencing of Cell-Free DNA from Cerebrospinal Fluid.
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Afflerbach, Ann-Kristin, Rohrandt, Christian, Brändl, Björn, Sönksen, Marthe, Hench, Jürgen, Frank, Stephan, Börnigen, Daniela, Alawi, Malik, Mynarek, Martin, Winkler, Beate, Ricklefs, Franz, Synowitz, Michael, Dührsen, Lasse, Rutkowski, Stefan, Wefers, Annika K, Müller, Franz-Josef, Schoof, Melanie, and Schüller, Ulrich
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- 2024
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27. Preeclampsia-induced cardiovascular diseases: identification of specific immune markers using Infinity Flow
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Humke, Charlotte, primary, Thiele, Kristin, additional, Pagenkemper, Mirja, additional, Maaß, Laura M., additional, Tallarek, Ann-Christin, additional, Hansen, Gudula, additional, Alawi, Malik, additional, Qi, Minyue, additional, Zeller, Tanja, additional, Nikolaev, Viacheslav, additional, Hecher, Kurt, additional, Arck, Petra C., additional, and Diemert, Anke, additional
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- 2023
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28. Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis
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Kempska, Joanna, primary, Oliveira-Ferrer, Leticia, additional, Grottke, Astrid, additional, Qi, Minyue, additional, Alawi, Malik, additional, Meyer, Felix, additional, Borgmann, Kerstin, additional, Hamester, Fabienne, additional, Eylmann, Kathrin, additional, Rossberg, Maila, additional, Smit, Daniel J., additional, Jücker, Manfred, additional, Laakmann, Elena, additional, Witzel, Isabell, additional, Schmalfeldt, Barbara, additional, Müller, Volkmar, additional, and Legler, Karen, additional
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- 2023
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29. Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection
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Thiele, Swantje, Stanelle-Bertram, Stephanie, Beck, Sebastian, Kouassi, Nancy Mounogou, Zickler, Martin, Müller, Martin, Tuku, Berfin, Resa-Infante, Patricia, van Riel, Debby, Alawi, Malik, Günther, Thomas, Rother, Franziska, Hügel, Stefanie, Reimering, Susanne, McHardy, Alice, Grundhoff, Adam, Brune, Wolfram, Osterhaus, Albert, Bader, Michael, Hartmann, Enno, and Gabriel, Gülsah
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- 2024
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30. Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients
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Renner, Sina, Schüler, Helke, Alawi, Malik, Kolbe, Verena, Rybczynski, Meike, Woitschach, Rixa, Sheikhzadeh, Sara, Stark, Veronika C., Olfe, Jakob, Roser, Elke, Seggewies, Friederike Sophia, Mahlmann, Adrian, Hempel, Maja, Hartmann, Melanie J., Hillebrand, Mathias, Wieczorek, Dagmar, Volk, Alexander Erich, Kloth, Katja, Koch-Hogrebe, Margarete, Abou Jamra, Rami, Mitter, Diana, Altmüller, Janine, Wey-Fabrizius, Alexandra, Petersen, Christine, Rau, Isabella, Borck, Guntram, Kubisch, Christian, Mir, Thomas S., von Kodolitsch, Yskert, Kutsche, Kerstin, and Rosenberger, Georg
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- 2019
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31. Novel poly-uridine insertion in the 3′UTR and E2 amino acid substitutions in a low virulent classical swine fever virus
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Coronado, Liani, Liniger, Matthias, Muñoz-González, Sara, Postel, Alexander, Pérez, Lester Josue, Pérez-Simó, Marta, Perera, Carmen Laura, Frías- Lepoureau, Maria Teresa, Rosell, Rosa, Grundhoff, Adam, Indenbirken, Daniela, Alawi, Malik, Fischer, Nicole, Becher, Paul, Ruggli, Nicolas, and Ganges, Llilianne
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- 2017
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32. Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape
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Mohme, Malte, Maire, Cecile L., Schliffke, Simon, Joosse, Simon A., Alawi, Malik, Matschke, Jakob, Schüller, Ulrich, Dierlamm, Judith, Martens, Tobias, Pantel, Klaus, Riethdorf, Sabine, Lamszus, Katrin, and Westphal, Manfred
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- 2020
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33. Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL
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zur Stadt, Udo, Alawi, Malik, Adao, Manuela, Indenbirken, Daniela, Escherich, Gabriele, and Horstmann, Martin A.
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- 2019
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34. DAMIAN: an open source bioinformatics tool for fast, systematic and cohort based analysis of microorganisms in diagnostic samples
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Alawi, Malik, Burkhardt, Lia, Indenbirken, Daniela, Reumann, Kerstin, Christopeit, Maximilian, Kröger, Nicolaus, Lütgehetmann, Marc, Aepfelbacher, Martin, Fischer, Nicole, and Grundhoff, Adam
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- 2019
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35. Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9
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Kortüm, Fanny, Jamra, Rami Abou, Alawi, Malik, Berry, Susan A., Borck, Guntram, Helbig, Katherine L., Tang, Sha, Huhle, Dagmar, Korenke, Georg Christoph, Hebbar, Malavika, Shukla, Anju, Girisha, Katta M., Steinlin, Maja, Waldmeier-Wilhelm, Sandra, Montomoli, Martino, Guerrini, Renzo, Lemke, Johannes R., and Kutsche, Kerstin
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- 2018
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36. Preclinical patient‐derived modeling of castration‐resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease
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Elsesy, Mohamed E., primary, Oh‐Hohenhorst, Su Jung, additional, Oing, Christoph, additional, Eckhardt, Alicia, additional, Burdak‐Rothkamm, Susanne, additional, Alawi, Malik, additional, Müller, Christian, additional, Schüller, Ulrich, additional, Maurer, Tobias, additional, von Amsberg, Gunhild, additional, Petersen, Cordula, additional, Rothkamm, Kai, additional, and Mansour, Wael Y., additional
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- 2023
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37. Murine scald models characterize the role of neutrophils and neutrophil extracellular traps in severe burns
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Elrod, Julia, primary, Lenz, Moritz, additional, Kiwit, Antonia, additional, Armbrust, Lina, additional, Schönfeld, Lavinia, additional, Reinshagen, Konrad, additional, Pagerols Raluy, Laia, additional, Mohr, Christoph, additional, Saygi, Ceren, additional, Alawi, Malik, additional, Rohde, Holger, additional, Herrmann, Martin, additional, and Boettcher, Michael, additional
- Published
- 2023
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38. Midgut Volvulus Adds a Murine, Neutrophil-Driven Model of Septic Condition to the Experimental Toolbox
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Elrod, Julia, primary, Kiwit, Antonia, additional, Lenz, Moritz, additional, Rohde, Holger, additional, Börnigen, Daniela, additional, Alawi, Malik, additional, Mohr, Christoph, additional, Pagerols Raluy, Laia, additional, Trochimiuk, Magdalena, additional, Knopf, Jasmin, additional, Reinshagen, Konrad, additional, Herrmann, Martin, additional, and Boettcher, Michael, additional
- Published
- 2023
- Full Text
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39. Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions
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Behrens, Kira, Triviai, Ioanna, Schwieger, Maike, Tekin, Nilgün, Alawi, Malik, Spohn, Michael, Indenbirken, Daniela, Ziegler, Marion, Müller, Ursula, Alexander, Warren S., and Stocking, Carol
- Published
- 2016
- Full Text
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40. A transplant “immunome” screening platform defines a targetable epitope fingerprint of multiple myeloma
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Schieferdecker, Aneta, Oberle, Anna, Thiele, Benjamin, Hofmann, Fabian, Göthel, Markus, Miethe, Sebastian, Hust, Michael, Braig, Friederike, Voigt, Mareike, von Pein, Ute-Marie, Koch-Nolte, Friedrich, Haag, Friedrich, Alawi, Malik, Indenbirken, Daniela, Grundhoff, Adam, Bokemeyer, Carsten, Bacher, Ulrike, Kröger, Nicolaus, and Binder, Mascha
- Published
- 2016
- Full Text
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41. Essential control of early B-cell development by Mef2 transcription factors
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Herglotz, Julia, Unrau, Ludmilla, Hauschildt, Friderike, Fischer, Meike, Kriebitzsch, Neele, Alawi, Malik, Indenbirken, Daniela, Spohn, Michael, Müller, Ursula, Ziegler, Marion, Schuh, Wolfgang, Jäck, Hans-Martin, and Stocking, Carol
- Published
- 2016
- Full Text
- View/download PDF
42. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, 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Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, 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Rozen, Steven G, Rubanova, Yulia, Rubio-Perez, Carlota, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Sahinalp, S Cenk, Saini, Natalie, Saito-Adachi, Mihoko, Saksena, Gordon, Salcedo, Adriana, Salgado, Roberto, Salichos, Leonidas, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sander, Chris, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlesner, Matthias, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schumacher, Steven E, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Scully, Ralph, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Shackleton, Mark, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Sidiropoulos, Nikos, Sieuwerts, Anieta M, Sieverling, Lina, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stenhouse, Alasdair, Stewart, Chip, Stilgenbauer, Stephan, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Torrents, David, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, MC Tubio, Jose, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Villasante, Izar, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Waddell, Nicola, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wala, Jeremiah A, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weischenfeldt, Joachim, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Mark H, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yao, Xiaotong, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yoon, Sung-Soo, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zamora, Jorge, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
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- 2023
- Full Text
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43. The landscape of viral associations in human cancers
- Author
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Zapatka, Marc, Borozan, Ivan, Brewer, Daniel S, Iskar, Murat, Grundhoff, Adam, Alawi, Malik, Desai, Nikita, Sültmann, Holger, Moch, Holger, PCAWG Pathogens, Cooper, Colin S, Eils, Roland, Ferretti, Vincent, Lichter, Peter, PCAWG Consortium, University of Zurich, and Lichter, Peter
- Subjects
Human Biology & Physiology ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,1311 Genetics ,Ecology,Evolution & Ethology ,10049 Institute of Pathology and Molecular Pathology ,610 Medicine & health ,Tumour Biology ,Genetics & Genomics ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and-for a subset-whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein-Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer.
- Published
- 2023
44. Combined burden and functional impact tests for cancer driver discovery using DriverPower
- Author
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Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, Claes, Wadi, Lina, Wang, Jiayin, Warrell, Jonathan, Waszak, Sebastian M, Weischenfeldt, Joachim, Wheeler, David A, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, von Mering, Christian, Gallinger, Steven, Aaltonen, Lauri A, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Berrios, Mario, Bersani, Samantha, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Boutros, Paul C, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chalmers, Don, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshpande, Vikram, Deshwar, Amit G, Desmedt, Christine, Dhalla, Noreen, Dhani, Neesha C, Dhir, Rajiv, DiBiase, Anthony, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gao, Jianjiong, Gao, Shengjie, Garraway, Levi, Garred, Øystein, Garrison, Erik, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grimmond, Sean M, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Gupta, Manaswi, Gupta, Shailja, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Haider, Syed, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Han, Leng, Hanna, George B, Hansmann, Martin, Harismendy, Olivier, Harliwong, Ivon, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Hersey, Peter, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Jiao, Wei, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kaiser, Vera B, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Kato, Mamoru, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, 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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
- Published
- 2023
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45. Integrative pathway enrichment analysis of multivariate omics data
- Author
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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
- Published
- 2023
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46. Pathway and network analysis of more than 2500 whole cancer genomes
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Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, 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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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47. Divergent mutational processes distinguish hypoxic and normoxic tumours
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
- Published
- 2023
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48. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, 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Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, 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Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, 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Christian
- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
- Published
- 2023
- Full Text
- View/download PDF
49. Emergence of daptomycin non-susceptibility in colonizing vancomycin-resistant Enterococcus faecium isolates during daptomycin therapy
- Author
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Lellek, Heinrich, Franke, Gefion C., Ruckert, Carolin, Wolters, Manuel, Wolschke, Christiane, Christner, Martin, Büttner, Henning, Alawi, Malik, Kröger, Nicolaus, and Rohde, Holger
- Published
- 2015
- Full Text
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50. Deciphering the microRNA signature of pathological cardiac hypertrophy by engineered heart tissue- and sequencing-technology
- Author
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Hirt, Marc N., Werner, Tessa, Indenbirken, Daniela, Alawi, Malik, Demin, Paul, Kunze, Ann-Cathrin, Stenzig, Justus, Starbatty, Jutta, Hansen, Arne, Fiedler, Jan, Thum, Thomas, and Eschenhagen, Thomas
- Published
- 2015
- Full Text
- View/download PDF
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