22 results on '"Ibberson, David"'
Search Results
2. Dispersive readout of industrially-fabricated silicon quantum dots
- Author
-
Ibberson, David J., Oulton, Ruth, and Harbord, Edmund
- Abstract
One of the most promising approaches to building a large-scale quantum computer is to encode qubits in the spin degree of freedom in silicon. Spin states in silicon have been shown to maintain coherence for timescales on the order of 10 milliseconds, allowing plenty of time for quantum operations to be performed. Small-scale devices have recently demonstrated single and two-qubit fidelities above the threshold for quantum error-correction protocols. The next challenge is to develop devices compatible with industrial fabrication that achieve similar performance, which can then be scaled up by exploiting VLSI capabilities of modern foundries. This thesis focuses on the problem of qubit readout, which is performed by spin-to-charge conversion in conjunction with a charge sensor. Gate-based dispersive readout is among the most scalable of approaches, for the reason that it does not require doped regions near to the qubit. The technique is performed by connecting an electrical resonator to a nearby gate electrode, then charge transitions can be detected via shifts in the resonant frequency. Both semi-classical and circuit-QED approaches are used to model the sensitivity. A tunable resonator is constructed and used to investigate the predicted conditions for optimal sensitivity, finding that impedance matching, low internal losses, and high characteristic impedance are desired. A superconducting resonator is then developed with a novel inductive coupling to the input line, which lends naturally to frequency multiplexing. Using this superconducting resonator, the circuit-QED regime is explored, measuring a charge-photon coupling strength sufficient for strong coupling. Fast charge detection is demonstrated in 50 nanoseconds, measuring a signal to noise ratio of 3.3. Finally, a method for spin manipulation in industrial nanowire devices is explored. To this end, electrical tunability of the valley-splitting is demonstrated via voltage applied to the silicon handle wafer or back-gate.
- Published
- 2022
3. Spatially Resolved Multi-Omics Single-Cell Analyses Inform Mechanisms of Immune Dysfunction in Pancreatic Cancer
- Author
-
Yousuf, Suhail, Qiu, Mengjie, Voith von Voithenberg, Lena, Hulkkonen, Johannes, Macinkovic, Igor, Schulz, Axel R., Hartmann, Domenic, Mueller, Florian, Mijatovic, Margarete, Ibberson, David, AlHalabi, Karam T., Hetzer, Jenny, Anders, Simon, Brüne, Bernhard, Mei, Henrik E., Imbusch, Charles D., Brors, Benedikt, Heikenwälder, Mathias, Gaida, Matthias M., Büchler, Markus W., Weigert, Andreas, Hackert, Thilo, and Roth, Susanne
- Published
- 2023
- Full Text
- View/download PDF
4. Extensive 5′-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast
- Author
-
Zhang, Yaqing, Kuster, David, Schmidt, Tobias, Kirrmaier, Daniel, Nübel, Gabriele, Ibberson, David, Benes, Vladimir, Hombauer, Hans, Knop, Michael, and Jäschke, Andres
- Published
- 2020
- Full Text
- View/download PDF
5. MediMer: a versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection.
- Author
-
Meyer, Marten, Parpoulas, Christina, Barthélémy, Titouan, Becker, Jonas P., Charoentong, Pornpimol, Lyu, Yanhong, Börsig, Selina, Bulbuc, Nadja, Tessmer, Claudia, Weinacht, Lisa, Ibberson, David, Schmidt, Patrick, Pipkorn, Rüdiger, Eichmüller, Stefan B., Steinberger, Peter, Lindner, Katharina, Poschke, Isabel, Platten, Michael, Fröhling, Stefan, and Riemer, Angelika B.
- Subjects
T cell receptors ,T cells ,ANTIGEN presenting cells ,PEPTIDOMIMETICS ,EUKARYOTIC cells ,RECOMBINANT molecules ,MELANOMA - Abstract
Peptide-loaded MHC class I (pMHC-I) multimers have revolutionized our capabilities to monitor disease-associated T cell responses with high sensitivity and specificity. To improve the discovery of T cell receptors (TCR) targeting neoantigens of individual tumor patients with recombinant MHC molecules, we developed a peptide-loadable MHC class I platform termed MediMer. MediMers are based on soluble disulfide-stabilized β2-microglobulin/heavy chain ectodomain single-chain dimers (dsSCD) that can be easily produced in large quantities in eukaryotic cells and tailored to individual patients’ HLA allotypes with only little hands-on time. Upon transient expression in CHO-S cells together with ER-targeted BirA biotin ligase, biotinylated dsSCD are purified from the cell supernatant and are ready to use. We show that CHO-produced dsSCD are free of endogenous peptide ligands. Empty dsSCD from more than 30 different HLAA,B,C allotypes, that were produced and validated so far, can be loaded with synthetic peptides matching the known binding criteria of the respective allotypes, and stored at low temperature without loss of binding activity. We demonstrate the usability of peptide-loaded dsSCD multimers for the detection of human antigen-specific T cells with comparable sensitivities as multimers generated with peptide-tethered β2m-HLA heavy chain single-chain trimers (SCT) and wild-type peptide-MHC-I complexes prior formed in small-scale refolding reactions. Using allotype-specific, fluorophore-labeled competitor peptides, we present a novel dsSCD-based peptide binding assay capable of interrogating large libraries of in silico predicted neoepitope peptides by flow cytometry in a high-throughput and rapid format. We discovered rare T cell populations with specificity for tumor neoepitopes and epitopes from shared tumor-associated antigens in peripheral blood of a melanoma patient including a so far unreported HLA-C*08:02-restricted NY-ESO-1-specific CD8
+ T cell population. Two representative TCR of this T cell population, which could be of potential value for a broader spectrum of patients, were identified by dsSCDguided single-cell sequencing and were validated by cognate pMHC-I multimer staining and functional responses to autologous peptide-pulsed antigen presenting cells. By deploying the technically accessible dsSCD MHC-I MediMer platform, we hope to significantly improve success rates for the discovery of personalized neoepitope-specific TCR in the future by being able to also cover rare HLA allotypes. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
6. Quantum Dot-Based Parametric Amplifiers
- Author
-
Cochrane, Laurence, Lundberg, Theodor, Ibberson, David J., Ibberson, Lisa, Hutin, Louis, Bertrand, Benoit, Stelmashenko, Nadia, Robinson, Jason W.A., Vinet, Maud, Seshia, Ashwin A., Gonzalez-Zalba, M. Fernando, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
- Subjects
electron ,noise ,FOS: Physical sciences ,magnetic field ,Applied Physics (physics.app-ph) ,cavity ,parametric ,microwaves ,[PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph] ,Mesoscale and Nanoscale Physics (cond-mat.mes-hall) ,[PHYS.COND]Physics [physics]/Condensed Matter [cond-mat] ,qubit ,[PHYS]Physics [physics] ,Quantum Physics ,Condensed Matter - Mesoscale and Nanoscale Physics ,superconductivity ,quantum dot ,high ,dissipation ,Physics - Applied Physics ,semiconductor ,amplifier ,duality ,readout ,nonlinear ,semiconductor detector ,Quantum Physics (quant-ph) ,performance - Abstract
Josephson parametric amplifiers (JPAs) approaching quantum-limited noise performance have been instrumental in enabling high fidelity readout of superconducting qubits and, recently, semiconductor quantum dots (QDs). We propose that the quantum capacitance arising in electronic two-level systems (the dual of Josephson inductance) can provide an alternative dissipation-less non-linear element for parametric amplification. We experimentally demonstrate phase-sensitive parametric amplification using a QD-reservoir electron transition in a CMOS nanowire split-gate transistor embedded in a 1.8~GHz superconducting lumped-element microwave cavity, achieving parametric gains of -3 to +3 dB, limited by Sisyphus dissipation. Using a semi-classical model, we find an optimised design within current technological capabilities could achieve gains and bandwidths comparable to JPAs, while providing complementary specifications with respect to integration in semiconductor platforms or operation at higher magnetic fields., 7 pages, 4 figures
- Published
- 2021
7. Non-reciprocal Pauli Spin Blockade in a Silicon Double Quantum Dot
- Author
-
Lundberg, Theodor, Ibberson, David J., Li, Jing, Hutin, Louis, Abadillo-Uriel, José C., Filippone, Michele, Bertrand, Benoit, Nunnenkamp, Andreas, Lee, Chang-Min, Stelmashenko, Nadia, Robinson, Jason W.A., Vinet, Maud, Ibberson, Lisa, Niquet, Yann-Michel, Gonzalez-Zalba, M. Fernando, Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), and Direction de Recherche Technologique (CEA) (DRT (CEA))
- Subjects
Quantum Physics ,Condensed Matter - Mesoscale and Nanoscale Physics ,FOS: Physical sciences ,silicon ,quantum dot ,computer: quantum ,electron: spin ,tunneling ,[PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph] ,Mesoscale and Nanoscale Physics (cond-mat.mes-hall) ,readout ,energy levels ,Pauli ,[PHYS.COND]Physics [physics]/Condensed Matter [cond-mat] ,Quantum Physics (quant-ph) ,qubit - Abstract
Spin qubits in gate-defined silicon quantum dots are receiving increased attention thanks to their potential for large-scale quantum computing. Readout of such spin qubits is done most accurately and scalably via Pauli spin blockade (PSB), however various mechanisms may lift PSB and complicate readout. In this work, we present an experimental observation of a new, highly prevalent PSB-lifting mechanism in a silicon double quantum dot due to incoherent tunneling between different spin manifolds. Through dispersively-detected magnetospectroscopy of the double quantum dot in 16 charge configurations, we find the mechanism to be energy-level selective and non-reciprocal for neighbouring charge configurations. Additionally, using input-output theory we report a large coupling of different electron spin manifolds of 7.90 $\mu$eV, the largest reported to date, indicating an enhanced spin-orbit coupling which may enable all-electrical qubit control., Comment: 12 pages, 10 figures. Minor updates to notation
- Published
- 2021
8. Transient cyclical methylation of promoter DNA
- Author
-
Kangaspeska, Sara, Stride, Brenda, Metivier, Raphael, Polycarpou-Schwarz, Maria, Ibberson, David, Carmouche, Richard Paul, Benes, Vladimir, Gannon, Frank, and Reid, George.
- Subjects
Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Methylation of CpG dinucleotides is generally associated with epigenetic silencing of transcription and is maintained through cellular division (1-3). Multiple CpG sequences are rare in mammalian genomes, but frequently occur [...]
- Published
- 2008
9. Cyclical DNA methylation of a transcriptionally active promoter
- Author
-
Metivier, Raphael, Gallais, Rozenn, Tiffoche, Christophe, Le Peron, Christine, Jurkowska, Renata Z., Carmouche, Richard P., Ibberson, David, Barath, Peter, Demay, Florence, Reid, George, Benes, Vladimir, Jeltsch, Albert, Gannon, Frank, and Salbert, Gilles
- Subjects
Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Processes that regulate gene transcription are directly under the influence of the genome organization. The epigenome contains additional information that is not brought by DNA sequence, and generates spatial and [...]
- Published
- 2008
10. Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor α, in response to deacetylase inhibition by valproic acid and trichostatin A
- Author
-
Reid, George, Métivier, Raphaël, Lin, Chin-Yo, Denger, Stefanie, Ibberson, David, Ivacevic, Tomi, Brand, Heike, Benes, Vladimir, Liu, Edison T, and Gannon, Frank
- Published
- 2005
- Full Text
- View/download PDF
11. Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli
- Author
-
Kahramanoglou, Christina, Seshasayee, Aswin S. N., Prieto, Ana I., Ibberson, David, Schmidt, Sabine, Zimmermann, Jurgen, Benes, Vladimir, Fraser, Gillian M., and Luscombe, Nicholas M.
- Published
- 2011
- Full Text
- View/download PDF
12. RH17 restricts reproductive fate and represses autonomous seed coat development in sexual Arabidopsis.
- Author
-
Stein, Ron Eric, Helge Nauerth, Berit, Binmöller, Laura, Zühl, Luise, Loreth, Anna, Reinert, Maximilian, Ibberson, David, and Schmidt, Anja
- Subjects
SEED development ,ASEXUAL reproduction ,GERM cells ,ARABIDOPSIS ,REGULATOR genes - Abstract
Plant sexual and asexual reproduction through seeds (apomixis) is tightly controlled by complex gene regulatory programs, which are not yet fully understood. Recent findings suggest that RNA helicases are required for plant germline development. This resembles their crucial roles in animals, where they are involved in controlling gene activity and the maintenance of genome integrity. Here, we identified previously unknown roles of Arabidopsis RH17 during reproductive development. Interestingly, RH17 is involved in repression of reproductive fate and of elements of seed development in the absence of fertilization. In lines carrying a mutant rh17 allele, development of supernumerary reproductive cell lineages in the female flower tissues (ovules) was observed, occasionally leading to formation of two embryos per seed. Furthermore, seed coat, and putatively also endosperm development, frequently initiated autonomously. Such induction of several features phenocopying distinct elements of apomixis by a single mutation is unusual and suggests that RH17 acts in regulatory control of plant reproductive development. Furthermore, an in-depth understanding of its action might be of use for agricultural applications. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
13. RNA degradation compromises the reliability of microRNA expression profiling
- Author
-
Muckenthaler Martina U, Benes Vladimir, Ibberson David, and Castoldi Mirco
- Subjects
Biotechnology ,TP248.13-248.65 - Abstract
Abstract Background MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression and their expression is frequently altered in human diseases, including cancer. To correlate clinically relevant parameters with microRNA expression, total RNA is frequently prepared from samples that were archived for various time periods in frozen tissue banks but, unfortunately, RNA integrity is not always preserved in these frozen tissues. Here, we investigate whether experimentally induced RNA degradation affects microRNA expression profiles. Results Tissue samples were maintained on ice for defined time periods prior to total RNA extraction, which resulted in different degrees of RNA degradation. MicroRNA expression was then analyzed by microarray analysis (miCHIP) or microRNA-specific real-time quantitative PCR (miQPCR). Our results demonstrate that the loss of RNA integrity leads to in unpredictability of microRNA expression profiles for both, array-based and miQPCR assays. Conclusion MicroRNA expression cannot be reliably profiled in degraded total RNA. For the profiling of microRNAs we recommend use of RNA samples with a RNA integrity number equal to or above seven.
- Published
- 2009
- Full Text
- View/download PDF
14. Gene Function Rather than Reproductive Mode Drives the Evolution of RNA Helicases in Sexual and Apomictic Boechera.
- Author
-
Kiefer, Markus, Nauerth, Berit H, Volkert, Christopher, Ibberson, David, Loreth, Anna, and Schmidt, Anja
- Subjects
HELICASES ,ASEXUAL reproduction ,GENETIC mutation ,RNA ,GENE families ,DNA helicases ,OVULES - Abstract
In higher plants, sexual and asexual reproductions through seeds (apomixis) have evolved as alternative strategies. Evolutionary advantages leading to coexistence of both reproductive modes are currently not well understood. It is expected that accumulation of deleterious mutations leads to a rapid elimination of apomictic lineages from populations. In this line, apomixis originated repeatedly, likely from deregulation of the sexual pathway, leading to alterations in the development of reproductive lineages (germlines) in apomicts as compared with sexual plants. This potentially involves mutations in genes controlling reproduction. Increasing evidence suggests that RNA helicases are crucial regulators of germline development. To gain insights into the evolution of 58 members of this diverse gene family in sexual and apomictic plants, we applied target enrichment combined with next-generation sequencing to identify allelic variants from 24 accessions of the genus Boechera , comprising sexual, facultative, and obligate apomicts. Interestingly, allelic variants from apomicts did not show consistently increased mutation frequency. Either sequences were highly conserved in any accession, or allelic variants preferentially harbored mutations in evolutionary less conserved C- and N-terminal domains, or presented high mutation load independent of the reproductive mode. Only for a few genes allelic variants harboring deleterious mutations were only identified in apomicts. To test if high sequence conservation correlates with roles in fundamental cellular or developmental processes, we analyzed Arabidopsis thaliana mutant lines in VASA-LIKE (VASL), and identified pleiotropic defects during ovule and reproductive development. This indicates that also in apomicts mechanisms of selection are in place based on gene function. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
15. Differential activity of F-box genes and E3 ligases distinguishes sexual versus apomictic germline specification in Boechera.
- Author
-
Zühl, Luise, Volkert, Christopher, Ibberson, David, and Schmidt, Anja
- Subjects
LIGASES ,GENE regulatory networks ,PLANT reproduction ,STEM cells ,REGULATOR genes ,OVULES ,UBIQUITINATION - Abstract
Germline specification is the first step during sexual and apomictic plant reproduction, and takes place in the nucellus of the ovule, a specialized domain of the reproductive flower tissues. In each case, a sporophytic cell is determined to form the sexual megaspore mother cell (MMC) or an apomictic initial cell (AIC). These differ in their developmental fates: while the MMC undergoes meiosis, the AIC modifies or omits meiosis to form the female gametophyte. Despite great interest in these distinct developmental processes, little is known about their gene regulatory basis. To elucidate the gene regulatory networks underlying germline specification, we conducted tissue-specific transcriptional profiling using laser-assisted microdissection and RNA sequencing to compare the transcriptomes of nucellar tissues between different sexual and apomictic Boechera accessions representing four species and two ploidy levels. This allowed us to distinguish between expression differences caused by genetic background or reproductive mode. Statistical data analysis revealed 45 genes that were significantly differentially expressed, and which potentially play a role for determination of the reproductive mode. Based on annotations, these included F-box genes and E3 ligases that most likely relate to genes previously described as regulators important for germline development. Our findings provide novel insights into the transcriptional basis of sexual and apomictic reproduction. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
16. Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods.
- Author
-
Mulindwa, Julius, Leiss, Kevin, Ibberson, David, Kamanyi Marucha, Kevin, Helbig, Claudia, Melo do Nascimento, Larissa, Silvester, Eleanor, Matthews, Keith, Matovu, Enock, Enyaru, John, and Clayton, Christine
- Subjects
TRYPANOSOMA brucei ,AFRICAN trypanosomiasis ,LABORATORY rodents ,CEREBROSPINAL fluid ,RNA sequencing - Abstract
All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of human patients with those of trypanosomes from culture and rodents. The data were aligned and analysed using new user-friendly applications designed for Kinetoplastid RNA-Seq data. The transcriptomes of trypanosomes from human blood and cerebrospinal fluid did not predict major metabolic differences that might affect drug susceptibility. Usefully, there were relatively few differences between the transcriptomes of trypanosomes from patients and those of similar trypanosomes grown in rats. Transcriptomes of monomorphic laboratory-adapted parasites grown in in vitro culture closely resembled those of the human parasites, but some differences were seen. In poly(A)-selected mRNA transcriptomes, mRNAs encoding some protein kinases and RNA-binding proteins were under-represented relative to mRNA that had not been poly(A) selected; further investigation revealed that the selection tends to result in loss of longer mRNAs. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
17. iDamIDseq and iDEAR: an improved method and computational pipeline to profile chromatin-binding proteins.
- Author
-
Gutierrez-Triana, Jose Arturo, Mateo, Juan L., Wittbrodt, Joachim, Ibberson, David, and Ryu, Soojin
- Subjects
TRANSCRIPTION factors ,CHROMATIN ,EPIGENETICS - Abstract
The article presents a report regarding the optimization of bacterial DNA adenine methyltransferase (Dam)-coding sequence that induces aberrant splicing when used with different promoters to drive tissue-specific expression, and profiling of chromatin-binding proteins.
- Published
- 2016
- Full Text
- View/download PDF
18. Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation.
- Author
-
Blake, Jonathon, Riddell, Andrew, Theiss, Susanne, Gonzalez, Alexis Perez, Haase, Bettina, Jauch, Anna, Janssen, Johannes W. G., Ibberson, David, Pavlinic, Dinko, Moog, Ute, Benes, Vladimir, and Runz, Heiko
- Subjects
CHROMOSOME abnormalities ,NUCLEOTIDES ,COGNITION disorders ,TRANSCRIPTION factors ,SCHIZOPHRENIA ,BIPOLAR disorder ,GENETICS - Abstract
Balanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
19. RNA Sequencing of Hepatobiliary Cancer Cell Lines: Data and Applications to Mutational and Transcriptomic Profiling.
- Author
-
Scherer, Dominique, Dávila López, Marcela, Goeppert, Benjamin, Abrahamsson, Sanna, González Silos, Rosa, Nova, Igor, Marcelain, Katherine, Roa, Juan C., Ibberson, David, Umu, Sinan U., Rounge, Trine Ballestad, Roessler, Stephanie, and Lorenzo Bermejo, Justo
- Subjects
ANIMAL experimentation ,CELL culture ,CELL lines ,GENE expression ,LIVER tumors ,GENETIC mutation ,BILE duct tumors ,GENE expression profiling ,SEQUENCE analysis ,IN vitro studies - Abstract
Simple Summary: Research on gallbladder cancer (GBC) has been largely neglected and molecular GBC data is underrepresented in public databases. Cancer cell lines constitute a valuable tool to examine the mechanisms of malignant transformation and identify potential therapeutic targets. Here we use RNA sequencing to characterize 23 commercial hepatobiliary cancer cell lines, including ten GBC cell lines, and provide detailed mutation and gene expression data to the research community. We illustrate the practical utility of the released information by (1) assessing the presence of specific mutations in the investigated cancer cell lines, (2) comparing global gene expression patterns in cell lines and primary biliary tumours and (3) examining the expression levels of specific genes. The released data and showcase applications will ease the design of in vitro cell culture assays for future studies. Cancer cell lines allow the identification of clinically relevant alterations and the prediction of drug response. However, sequencing data for hepatobiliary cancer cell lines in general, and particularly gallbladder cancer (GBC), are sparse. Here, we apply RNA sequencing to characterize 10 GBC, eight hepatocellular carcinoma, and five cholangiocarcinoma (CCA) cell lines. RNA extraction, quality control, library preparation, sequencing, and pre-processing of sequencing data were implemented using state-of-the-art techniques. Public data from the MSK-IMPACT database and a large cohort of Japanese biliary tract cancer patients were used to illustrate the usage of the released data. The total number of exonic mutations varied from 7207 for the cell line NOZ to 9760 for HuCCT1. Researchers planning experiments that require TP53 mutations could use the cell lines NOZ, OCUG-1, SNU308, or YoMi. Mz-Cha-1 showed mutations in ATM, SNU308 presented SMAD4 mutations, and the only investigated cell line that showed ARID1A mutations was GB-d1. SNU478 was the cell line with the global gene expression pattern most similar to GBC, intrahepatic CCA, and extrahepatic CCA. EGFR, KMT2D, and KMT2C generally presented a higher expression in the investigated cell lines than in Japanese primary GBC tumors. We provide the scientific community with detailed mutation and gene expression data, together with three showcase applications, with the aim of facilitating the design of future in vitro cell culture assays for research on hepatobiliary cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. Cyclical DNA methylation of a transcriptionally active promoter.
- Author
-
Métivier, Raphaël, Gallais, Rozenn, Tiffoche, Christophe, Le Péron, Christine, Jurkowska, Renata Z., Carmouche, Richard P., Ibberson, David, Barath, Peter, Demay, Florence, Reid, George, Benes, Vladimir, Jeltsch, Albert, Gannon, Frank, and Salbert, Gilles
- Subjects
DNA - Abstract
A correction to the article "Cyclical DNA methylation of a transcriptionally active promoter" that was published in "Nature" in the 2008 issue is presented.
- Published
- 2010
- Full Text
- View/download PDF
21. Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.
- Author
-
Huth T, Dreher EC, Lemke S, Fritzsche S, Sugiyanto RN, Castven D, Ibberson D, Sticht C, Eiteneuer E, Jauch A, Pusch S, Albrecht T, Goeppert B, Candia J, Wang XW, Ji J, Marquardt JU, Nahnsen S, Schirmacher P, and Roessler S
- Subjects
- Humans, Chromosome Deletion, Chromosome Aberrations, Chromosomes, CRISPR-Cas Systems, Synthetic Lethal Mutations, Liver Neoplasms genetics, Liver Neoplasms pathology
- Abstract
Large-scale chromosomal aberrations are prevalent in human cancer, but their function remains poorly understood. We established chromosome-engineered hepatocellular carcinoma cell lines using CRISPR-Cas9 genome editing. A 33-mega-base pair region on chromosome 8p (chr8p) was heterozygously deleted, mimicking a frequently observed chromosomal deletion. Using this isogenic model system, we delineated the functional consequences of chr8p loss and its impact on metastatic behavior and patient survival. We found that metastasis-associated genes on chr8p act in concert to induce an aggressive and invasive phenotype characteristic for chr8p-deleted tumors. Genome-wide CRISPR-Cas9 viability screening in isogenic chr8p-deleted cells served as a powerful tool to find previously unidentified synthetic lethal targets and vulnerabilities accompanying patient-specific chromosomal alterations. Using this target identification strategy, we showed that chr8p deletion sensitizes tumor cells to targeting of the reactive oxygen sanitizing enzyme Nudix hydrolase 17. Thus, chromosomal engineering allowed for the identification of novel synthetic lethalities specific to chr8p loss of heterozygosity.
- Published
- 2023
- Full Text
- View/download PDF
22. RNA degradation compromises the reliability of microRNA expression profiling.
- Author
-
Ibberson D, Benes V, Muckenthaler MU, and Castoldi M
- Subjects
- Animals, Cluster Analysis, Female, Mice, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling methods, MicroRNAs metabolism, RNA Stability
- Abstract
Background: MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression and their expression is frequently altered in human diseases, including cancer. To correlate clinically relevant parameters with microRNA expression, total RNA is frequently prepared from samples that were archived for various time periods in frozen tissue banks but, unfortunately, RNA integrity is not always preserved in these frozen tissues. Here, we investigate whether experimentally induced RNA degradation affects microRNA expression profiles., Results: Tissue samples were maintained on ice for defined time periods prior to total RNA extraction, which resulted in different degrees of RNA degradation. MicroRNA expression was then analyzed by microarray analysis (miCHIP) or microRNA-specific real-time quantitative PCR (miQPCR). Our results demonstrate that the loss of RNA integrity leads to in unpredictability of microRNA expression profiles for both, array-based and miQPCR assays., Conclusion: MicroRNA expression cannot be reliably profiled in degraded total RNA. For the profiling of microRNAs we recommend use of RNA samples with a RNA integrity number equal to or above seven.
- Published
- 2009
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.