Academic literature on the topic 'Transcriptomic alterations'
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Journal articles on the topic "Transcriptomic alterations"
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Ekeuku, Sophia Ogechi, Nuraqila Mohd Murshid, Siti Nursyazwani Shukri, Nur Fatin Nabilah Mohd Sahardi, and Suzana Makpol. "Effect of Vitamin E on Transcriptomic Alterations in Alzheimer’s Disease." International Journal of Molecular Sciences 24, no. 15 (August 3, 2023): 12372. http://dx.doi.org/10.3390/ijms241512372.
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Research into ageing is focused on understanding why some people can maintain cognitive ability and others lose autonomy, affecting their quality of life. Studies have revealed that age-related neurodegenerative disorders like Alzheimer’s disease (AD) are now major causes of death among the elderly, surpassing malignancy. This review examines the effects of vitamin E on transcriptomic changes in ageing and neurodegenerative diseases, using AD as an example, and how different transcriptome profiling techniques can shape the results. Despite mixed results from transcriptomic studies on AD patients’ brains, we think advanced technologies could offer a more detailed and accurate tool for such analysis. Research has also demonstrated the role of antioxidant modifiers in preventing AD. This review will explore the key findings regarding AD and its modulation by vitamin E, emphasizing the shift in its epidemiology during the ageing process.
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Marano, Domenico, Salvatore Fioriniello, Maurizio D’Esposito, and Floriana Della Ragione. "Transcriptomic and Epigenomic Landscape in Rett Syndrome." Biomolecules 11, no. 7 (June 30, 2021): 967. http://dx.doi.org/10.3390/biom11070967.
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Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2 is a master epigenetic modulator of gene expression, with a role in the organization of global chromatin architecture. Based on its interaction with multiple molecular partners and the diverse epigenetic scenario, MeCP2 triggers several downstream mechanisms, also influencing the epigenetic context, and thus leading to transcriptional activation or repression. In this frame, it is conceivable that defects in such a multifaceted factor as MeCP2 lead to large-scale alterations of the epigenome, ranging from an unbalanced deposition of epigenetic modifications to a transcriptional alteration of both protein-coding and non-coding genes, with critical consequences on multiple downstream biological processes. In this review, we provide an overview of the current knowledge concerning the transcriptomic and epigenomic alterations found in RTT patients and animal models.
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Ahn, Antonio, Euan J. Rodger, Jyoti Motwani, Gregory Gimenez, Peter A. Stockwell, Matthew Parry, Peter Hersey, Aniruddha Chatterjee, and Michael R. Eccles. "Transcriptional Reprogramming and Constitutive PD-L1 Expression in Melanoma Are Associated with Dedifferentiation and Activation of Interferon and Tumour Necrosis Factor Signalling Pathways." Cancers 13, no. 17 (August 24, 2021): 4250. http://dx.doi.org/10.3390/cancers13174250.
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Melanoma is the most aggressive type of skin cancer, with increasing incidence worldwide. Advances in targeted therapy and immunotherapy have improved the survival of melanoma patients experiencing recurrent disease, but unfortunately treatment resistance frequently reduces patient survival. Resistance to targeted therapy is associated with transcriptomic changes and has also been shown to be accompanied by increased expression of programmed death ligand 1 (PD-L1), a potent inhibitor of immune response. Intrinsic upregulation of PD-L1 is associated with genome-wide DNA hypomethylation and widespread alterations in gene expression in melanoma cell lines. However, an in-depth analysis of the transcriptomic landscape of melanoma cells with intrinsically upregulated PD-L1 expression is lacking. To determine the transcriptomic landscape of intrinsically upregulated PD-L1 expression in melanoma, we investigated transcriptomes in melanomas with constitutive versus inducible PD-L1 expression (referred to as PD-L1CON and PD-L1IND). RNA-Seq analysis was performed on seven PD-L1CON melanoma cell lines and ten melanoma cell lines with low inducible PD-L1IND expression. We observed that PD-L1CON melanoma cells had a reprogrammed transcriptome with a characteristic pattern of dedifferentiated gene expression, together with active interferon (IFN) and tumour necrosis factor (TNF) signalling pathways. Furthermore, we identified key transcription factors that were also differentially expressed in PD-L1CON versus PD-L1IND melanoma cell lines. Overall, our studies describe transcriptomic reprogramming of melanomas with PD-L1CON expression.
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Mattei, Daniele, Andranik Ivanov, Marc van Oostrum, Stanislav Pantelyushin, Juliet Richetto, Flavia Mueller, Michal Beffinger, et al. "Enzymatic Dissociation Induces Transcriptional and Proteotype Bias in Brain Cell Populations." International Journal of Molecular Sciences 21, no. 21 (October 26, 2020): 7944. http://dx.doi.org/10.3390/ijms21217944.
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Different cell isolation techniques exist for transcriptomic and proteotype profiling of brain cells. Here, we provide a systematic investigation of the influence of different cell isolation protocols on transcriptional and proteotype profiles in mouse brain tissue by taking into account single-cell transcriptomics of brain cells, proteotypes of microglia and astrocytes, and flow cytometric analysis of microglia. We show that standard enzymatic digestion of brain tissue at 37 °C induces profound and consistent alterations in the transcriptome and proteotype of neuronal and glial cells, as compared to an optimized mechanical dissociation protocol at 4 °C. These findings emphasize the risk of introducing technical biases and biological artifacts when implementing enzymatic digestion-based isolation methods for brain cell analyses.
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Dufva, Olli, Petri Pölönen, Oscar Brück, Mikko A. Keränen, Juha Mehtonen, Sanna M. Siitonen, Suvi-Katri Leivonen, et al. "Immunogenomic Landscape of Hematological Malignancies." Blood 132, Supplement 1 (November 29, 2018): 2596. http://dx.doi.org/10.1182/blood-2018-99-118335.
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Abstract Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. How cancer-cell intrinsic genomic and epigenetic alterations influence immune signatures in hematological malignancies is not known. Here, we integrated over 8,000 transcriptomes of hematologic cancers and multilevel genomic datasets to investigate associations of immune states to cancer molecular subtypes, genetic and epigenetic alterations, and clinical outcomes. We utilized a resource of over 8,000 transcriptomes collected across 36 hematologic malignancies and normal hematopoietic cells (Hemap), together with multi-omics datasets of acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) from The Cancer Genome Atlas and other sources (Figure). In addition to gene expression data, we integrated somatic DNA alterations, methylation data, multiplex immunohistochemistry (mIHC), and flow cytometry to comprehensively map immune-associated features and validate the robustness of the findings. To characterize the composition of the cytolytic immune infiltrate from bulk transcriptomes, we defined a signature of genes most specifically expressed in cytotoxic CD8+ T lymphocytes and natural killer (NK) cells termed cytolytic score. We found significant heterogeneity in the cytotoxic lymphocyte infiltration signature across hematologic malignancies. Highest cytolytic infiltrate was detected in lymphomas and correlated with IFN-γ and myeloid cell infiltration signatures including CXCL9-11 and IDO1, distinguishing the lymphoma microenvironment from leukemias. In addition to transcriptomic microenvironmental properties, specific genetic alterations were associated with cytotoxic lymphocyte infiltration. In DLBCL, driver alterations enriched in the germinal center B-cell like (GCB) molecular subtype including BCL2 translocations and KMT2D were linked to an immune-cold transcriptomic phenotype. In contrast, DTX1 alterations defined immune-infiltrated lymphomas within the GCB molecular subtype. In AML, TP53 mutations and complex karyotype were enriched in a distinct tSNE-based transcriptomic cluster characterized by increased immune infiltration in the bone marrow (BM). Given the importance of effective antigen presentation for adaptive anti-tumor immune responses, we aimed to understand the transcriptional regulation of HLA genes and co-stimulatory and co-inhibitory signaling in subtypes of hematological malignancies. Downregulation of the antigen-presenting HLA II genes was associated with CpG methylation of the promoter region of the HLA class II master regulator CIITA in distinct transcriptomic clusters of AML harboring PML-RARA or NPM1 alterations. Expression of genes encoding immune checkpoint molecules was strongly influenced by the cell-of-origin and microenvironment of each cancer type. We identified novel associations of inhibitory immune checkpoint molecules to disease subtypes, such as VISTA/PD1-H enriched in myeloid malignancies including AML, CML, and MDS, validated by mIHC performed on BM biopsies. Furthermore, variation in the expression of several genes encoding immune checkpoints was associated with somatic mutations (e.g. CD70 in DLBCL), copy-number alterations (e.g. MICB in DLBCL), and DNA methylation (e.g. PDL1 and PDCD1LG2 in AML). Finally, we integrated GTEx gene expression data across tissues to define cancer-germline antigens (CGAs) with an immune privileged tissue expression pattern. CGAs were frequently expressed in multiple myeloma and DLBCL compared to other hematologic malignancies. CGA expression was associated with cytogenetic alterations and increased MYC activity signature in myeloma and CD58 and KLHL6 mutations in DLBCL. In addition, CGA expression in myeloma and DLBCL was linked to reduced antigen gene promoter methylation and decreased survival. In summary, our findings demonstrate that molecular subtypes of hematological malignancies harbor distinct immunological signatures influenced by genetic and epigenetic alterations. Integrating genetic, epigenetic, and transcriptomic data may facilitate the development of precision immune intervention strategies in hematological malignancies. Figure. Figure. Disclosures Leppa: Bayer: Research Funding; Celgene: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Mustjoki:Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria; Pfizer: Honoraria, Research Funding; Ariad: Research Funding; Novartis: Honoraria, Research Funding.
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Abida, Wassim, Joanna Cyrta, Glenn Heller, Davide Prandi, Joshua Armenia, Ilsa Coleman, Marcin Cieslik, et al. "Genomic correlates of clinical outcome in advanced prostate cancer." Proceedings of the National Academy of Sciences 116, no. 23 (May 6, 2019): 11428–36. http://dx.doi.org/10.1073/pnas.1902651116.
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Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about the impact of this heterogeneity on clinical outcome. Here, we report comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer (mCRPC) linked with longitudinal clinical outcomes, integrating findings from whole-exome, transcriptome, and histologic analysis. For 128 patients treated with a first-line next-generation androgen receptor signaling inhibitor (ARSI; abiraterone or enzalutamide), we examined the association of 18 recurrent DNA- and RNA-based genomic alterations, including androgen receptor (AR) variant expression, AR transcriptional output, and neuroendocrine expression signatures, with clinical outcomes. Of these, only RB1 alteration was significantly associated with poor survival, whereas alterations in RB1, AR, and TP53 were associated with shorter time on treatment with an ARSI. This large analysis integrating mCRPC genomics with histology and clinical outcomes identifies RB1 genomic alteration as a potent predictor of poor outcome, and is a community resource for further interrogation of clinical and molecular associations.
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Sindona, Cinzia, Michele Runci Anastasi, Luigi Chiricosta, Agnese Gugliandolo, Serena Silvestro, Placido Bramanti, Piero Cascone, and Emanuela Mazzon. "Temporomandibular Disorders Slow Down the Regeneration Process of Masticatory Muscles: Transcriptomic Analysis." Medicina 57, no. 4 (April 7, 2021): 354. http://dx.doi.org/10.3390/medicina57040354.
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Background and Objectives: Musculoskeletal injuries represent a pathological condition due to limited joint motility and morphological and functional alterations of the muscles. Temporomandibular disorders (TMDs) are pathological conditions due to alterations in the musculoskeletal system. TMDs mainly cause temporomandibular joint and masticatory muscle dysfunctions following trauma, along with various pathologies and inflammatory processes. TMD affects approximately 15% of the population and causes malocclusion problems and common symptoms such as myofascial pain and migraine. The aim of this work was to provide a transcriptomic profile of masticatory muscles obtained from TMD migraine patients compared to control. Materials and Methods: We used Next Generation Sequencing (NGS) technology to evaluate transcriptomes in masseter and temporalis muscle samples. Results: The transcriptomic analysis showed a prevalent downregulation of the genes involved in the myogenesis process. Conclusions: In conclusion, our findings suggest that the muscle regeneration process in TMD migraine patients may be slowed, therefore therapeutic interventions are needed to restore temporomandibular joint function and promote healing processes.
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Aschauer, Lydia, Leonhard N. Gruber, Alice Limonciel, Martin O. Leonhard, Walter Pfaller, Anja Wilmes, and Paul Jennings. "Transcriptomic and functional alterations during renal epithelial maturation." Toxicology Letters 211 (June 2012): S161. http://dx.doi.org/10.1016/j.toxlet.2012.03.584.
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Goldenberg, Regina Coeli dos Santos, Dumitru A. Iacobas, Sanda Iacobas, Leonardo Lima Rocha, Fabio da Silva de Azevedo Fortes, Leandro Vairo, Fnu Nagajyothi, Antonio Carlos Campos de Carvalho, Herbert B. Tanowitz, and David C. Spray. "Transcriptomic alterations in Trypanosoma cruzi-infected cardiac myocytes." Microbes and Infection 11, no. 14-15 (December 2009): 1140–49. http://dx.doi.org/10.1016/j.micinf.2009.08.009.
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Han, Seong Kyu, Jungho Kong, Sanguk Kim, Jae‐Hoon Lee, and Dong‐Hoo Han. "Exomic and transcriptomic alterations of hereditary gingival fibromatosis." Oral Diseases 25, no. 5 (April 15, 2019): 1374–83. http://dx.doi.org/10.1111/odi.13093.
Full textDissertations / Theses on the topic "Transcriptomic alterations"
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Benvenuto, Giuseppe. "A bioinformatic approach to define transcriptome alterations in platinum resistance ovarian cancers." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3424723.
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Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy due to its diagnosis at advanced stages, when the disease has already spread beyond the ovaries. EOC is generally sensitive to first line chemotherapy, and the vast majority of patients respond to platinum (Pt)-based therapy after debulking surgery.
Unfortunately, more than 80% of Pt-responsive patients relapse with a disease that progressively becomes Pt-resistant. Based mainly on clinical evidence, the process by which disease relapses is still poorly understood. The aim is to identify biomarkers of sensitivity to chemotherapy and therapeutic targets in HGS-EOC by integrating transcriptomic data, coding and non-coding RNAs. The bioinformatic analysis was applied on microarray data and RNA-seq data, embracing different classes of patients (resistant, sensitive, partially sensitive and normal).
Two complementary approaches have been adopted to identify biomarkers of therapy response in microarray data: i) a classic approach and ii) a network-based approach using micrographite. The results obtained with both procedures have then been used to reconstruct a regulatory circuit involved in therapy response. The final outcome is a regulatory cell signal pathway composed of genes and miRNAs mainly involved in the therapy response. Circuit has been validated using two external and independent cohorts by quantitative real-time PCR (qRT-PCR). However, in order to complete the characterization of network as prognostic factor we decided to consider in survival analysis defect of the Homologous Recombination (HR). Approaching in survival analysis, a signature of three genes (SDF2L1, PPP1R12A and PRKG1) found to be independent prognostic biomarkers, was able to predict, at the time of diagnosis, resistance to Pt-based chemotherapy.
Also, a new approach has been evaluated in order to characterize new mechanisms of chemotherapy resistance in ovarian cancers. On microarray data, we tried to stratify patients for the immunotherapy, with recent improved understanding of the immune recognition and regulation of cancer cells. In addition, using RNA-seq data and somatic DNA mutations, we went deeper in immunogenicity of ovarian cancer trying to find new elements as therapy targets, neoantigens, not associated to this tumor till now.
At last, in addition, the small amount of molecular differences between Pt-r and Pt-s patients suggested the presence of potential new transcripts involved in therapy response maybe due to aberrant splicing events. To investigate this hypothesis, we used a set of RNA-seq experiments, to identify new aberrant splicing such as circular RNAs. We reported 5 circRNAs differentially expressed between tumour resistance types, and a large number of class-specific circRNAs. In particular, circ_BARD1 showed a character as prognostic factor significative in OS and PFS, in multivariate analysis with residual tumour and age as covariates. The consistency of circular RNA expression, in conjunction with the regulatory circuit, may offer new candidates for cancer treatment and prognosis, revealing that the integration of coding and non-coding RNAs data may shed light on chemotherapy resistance mechanisms in ovarian cancer.
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Danielson, Steven Richard. "Apoptosis and transcriptomal alterations in Leber's Hereditary Optic Neuropathy /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.
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Souza, Leonardo da Cunha Menezes. "Mecanismos de Cardiotoxicidade da Doxorrubicina em Ratos Wistar e Potencial Cardioprotetor da Alda-1." Botucatu, 2019. http://hdl.handle.net/11449/180952.
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Orientador: Daisy Maria Fávero SalvadoriResumo: A cardiotoxicidade induzida pela doxorrubicina (DOX), antraciclina isolada da actinobacteria Streptomyces peucetius e amplamente utilizada na terapia antineoplásica, corresponde a um dos mais importantes eventos patofisiológicos que limitam sua aplicação clínica. No entanto, não são completamente conhecidos todos os mecanismos envolvidos nessa toxicidade, o que diminui as possiblidades de intervenção e a redução dos efeitos colaterais para os pacientes sob tratamento. Uma das hipósteses é que os aldeídos gerados pela ação da DOX atuam sobre membranas mitocondriais, alterando o estado redox e formando adutos com proteínas, os quais prejudicam o correto funcionamento da organela. Atividades deletérias da DOX sobre outros componentes celulares, como, por exemplo, os ácidos ribonucleicos, são, também, possíveis mecanismos de toxicidade do antineoplásico. Várias estratégias têm sido utilizadas para minimizar os efeitos adversos da DOX. Uma delas, é a busca por compostos que possam proteger as células da ação citotóxica. Nesse sentido, a Alda-1, pertencente ao grupo das chaperonas e agonista da enzima aldeído desidrogenase mitocondrial (ALDH2), vem sendo testada com o objetivo de reduzir os efeitos adversos dos metabólitos e radicais gerados pelo antineoplásico. Para investigar outros possíveis mecanismos de ação da DOX e o efeito cardiprotetor da Alda-1, este estudo foi delineado utilizando duas abordagens distintas: experimentos in vivo, com ratos Wistar machos submetidos a trata... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The cardiotoxicity induced by doxorubicin (DOX), anthracycline isolated from the actinobacteria Streptomyces peucetius, and widely used as an antineoplastic drug, is one of the most important pathophysiological events that limit its clinical application. However, all the mechanisms involved in this toxicity are not fully understood. One hypothesis is that the aldehydes generated by DOX act on mitochondrial membranes, modifying the redox state and proting adducts with proteins. DOX activities on other cellular components, such as ribonucleic acids, are also possible mechanisms of toxicity. Several strategies have been used to reduce the DOX adverse effects. One of them is the identification of compounds that can protect cells against cytotoxic. Alda-1, which belongs to a group of chaperones and is an agonist of the mitochondrial aldehyde dehydrogenase (ALDH2), has been tested to reduce the adverse effects of metabolites and radicals generated by DOX. To investigate other possible DOX mechanisms of action, and the cardioprotective activity of Alda-1, this study was designed using two different approaches: in vivo, with male Wistar rats submitted to acute and chronic treatments; and, in vitro, in mice fibroblasts and cybrids with ND5 (gene that encodes the mitochondrial Complex I subunit) mitochondrial gene heteroplasmy. The expression profiling of genes related to beta oxidation pathways, Bax, Bcl-2, C1QBP, ALDH2 and miR34a microRNA (ALDH2 expression regulator), and the lipoper... (Complete abstract click electronic access below)
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Rahmani, Alexandra. "Identification des facteurs de pathogénicité de la bactérie Vibrio tapetis, responsable de la maladie de l'anneau brun chez la palourde japonaise Ruditapes philippinarum et de mortalités chez les poissons marins Transcriptomic analysis of clam extrapallial fluids reveals immunity and cytoskeleton alterations in the first week of Brown Ring Disease development, in Fish & Shellfish Immunology 93, October 2019." Thesis, Brest, 2019. http://www.theses.fr/2019BRES0059.
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L’objectif principal de cette thèse est d’étudier les mécanismes liés au pouvoir pathogène de V. tapetis.Pour cela, nous avons développé 2 axes de recherche. Le premier axe vise à étudier la virulence de V. tapetis en répondant aux 2 problématiques suivantes : Quels sont les gènes impliqués dans la virulence de V. tapetis ? et Existe-t-il des marqueurs hôtes-spécifiques de la virulence de V. tapetis ? Le second axe de recherche concerne l’interaction hôte pathogène et répond aux 2 problématiques suivantes : Quels sont les gènes exprimés lors de l’infection chez l’hôte ? et Quelles sont les modulations au sein de l’animal associées au pH et à la température lors de l’infection ?Les principales découvertes de cette thèse sont : (i) La bactérie V. tapetis, dans le cadre de la MAB, induit une sous expression des gènes impliqués dans la réponseimmunitaire et une dérégulation des gènes impliqués dans la stabilisation et la synthèse des filaments d’actine (ii) Ce pathogène induit également une diminution de l’activité lysosomale sur les hémocytes exposés (iii) L’effet de V. tapetis sur le cytosquelette d’actine et sur la diminution de l’activité lysosomale est indépendante du système de sécrétion de type IV (T4SS) (iv) Le système de sécrétion de type IV (T4SS) est impliqué dans le développement de la MAB mais n’est pas essentiel pour induire cette affection(v) Dans le cadre de la MAB et de la perte des adhérences des hémocytes in vitro, V. tapetis est capable de moduler le pH des fluides extra-palléaux, respectivement dans les premiers jours et premières heures de l’infection (vi) Enfin, l’approche de « strains typing » basée sur la technique MALDI-TOF permet de discriminer les souches de V. tapetis en fonction de leur pouvoir pathogène vis à vis de la palourde japonaiseThe main objective of this thesis is to study the mechanisms related to the pathogenicity of V. tapetis. For this purpose, we developed 2 research axes. The first one aimed at studying the virulence of V. tapetis by answering the following 2 issues: What are the genes involved in the virulence of V. tapetis? and Are there host-specific markers of the virulence of V. tapetis? The second research axis concerned pathogen-host interactions and addressed the following 2 issues: What are the genes expressed during infection in the host? and What are the modulations in the animal associated with pH and temperature during infection? The main findings of this thesis are: (i) V. tapetis, in the context of BRD, induces a down expression of genes involved in the immune response anda deregulation of genes involved in the stabilization and synthesis of actin filaments (ii) This pathogen also induces a decrease in lysosomal activity on exposed hemocytes (iii) The effect of V. tapetis on the actin cytoskeleton and on the decrease in lysosomal activity is independent of the type IV secretion system (T4SS) (iv) The type IV secretion system (T4SS) is involved in the development of BRD but is not essential to induce this disease (v) In the context of BRD and of the loss of hemocyte adhesions properties in vitro, V. tapetis is able to modulate the pH of extrapallial fluids, respectively in the first days and hours of infection (vi) Finally, the "strains typing" approach based on MALDITOF makes it possible to discriminate between V. tapetis strains according to their pathogenicity with regard to Manila clam
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Bezerra, Ana Rita Macedo. "Molecular genomics of a genetic code alteration." Doctoral thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12499.
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Doutoramento em BiologiaThe genetic code is not universal. Alterations to its standard form have been discovered in both prokaryotes and eukaryotes and demolished the dogma of an immutable code. For instance, several Candida species translate the standard leucine CUG codon as serine. In the case of the human pathogen Candida albicans, a serine tRNA (tRNACAGSer) incorporates in vivo 97% of serine and 3% of leucine in proteins at CUG sites. Such ambiguity is flexible and the level of leucine incorporation increases significantly in response to environmental stress. To elucidate the function of such ambiguity and clarify whether the identity of the CUG codon could be reverted from serine back to leucine, we have developed a forced evolution strategy to increase leucine incorporation at CUGs and a fluorescent reporter system to monitor such incorporation in vivo. Leucine misincorporation increased from 3% up to nearly 100%, reverting CUG identity from serine back to leucine. Growth assays showed that increasing leucine incorporation produced impressive arrays of phenotypes of high adaptive potential. In particular, strains with high levels of leucine misincorporation exhibited novel phenotypes and high level of tolerance to antifungals. Whole genome re-sequencing revealed that increasing levels of leucine incorporation were associated with accumulation of single nucleotide polymorphisms (SNPs) and loss of heterozygozity (LOH) in the higher misincorporating strains. SNPs accumulated preferentially in genes involved in cell adhesion, filamentous growth and biofilm formation, indicating that C. albicans uses its natural CUG ambiguity to increase genetic diversity in pathogenesis and drug resistance related processes. The overall data provided evidence for unantecipated flexibility of the C. albicans genetic code and highlighted new roles of codon ambiguity on the evolution of genetic and phenotypic diversity.
O código genético não é universal. Alterações à identidade de vários codões descobertas em procariotas e eucariotas invalidam a hipótese dum código genético universal e imutável. Por exemplo, várias espécies do género Candida traduzem o codão CUG de leucina como serina. Em Candida albicans, um único tRNA de serina (tRNACAGSer) incorpora in vivo 97% de serina e 3% de leucina nas proteínas em resposta a codões CUG presentes nos mRNAs deste fungo patogénico. Esta ambiguidade é flexível e a incorporação de leucina aumenta em condições de stress. De forma a elucidar a função desta ambiguidade e determinar se a identidade dos codões CUG podia ser revertida de serina para leucina, desenvolvemos uma estratégia de evolução forçada e uma proteína recombinante fluorescente cuja actividade depende da incorporação de leucina num codão CUG. Construímos estirpes que incorporam leucina nas proteínas em resposta a codões CUGs em níveis que variam entre 0,64% e 98,46%. Esta reversão de uma alteração ao código genético demostrou de modo inequívoco que o código é flexível e pode evoluir. Testes de crescimento em diferentes meios de cultivo revelaram uma série impressionante de fenótipos com elevado potencial adaptativo nas estirpes mais ambíguas, nomeadamente tolerância a antifúngicos. A sequenciação dos genomas das estirpes que construímos revelou que a ambiguidade do codão CUG resulta na acumulação de polimorfismos de nucleótido únicos (SNP) no genoma. Verificámos também perda de heterozigozidade (LOH) nos cromossomas 5 e R das estirpes que incorporam 80,84% e 98,46% de leucina em locais proteicos codificados por codões CUG. Os SNPs acumularam-se preferencialmente em genes envolvidos na adesão celular, no crescimento filamentoso e na formação de biofilmes, sugerindo que C. albicans utiliza a sua ambiguidade natural para aumentar a diversidade genética dos processos relacionados com a patogénese e resistência a drogas. Estes resultados evidenciam uma notável flexibilidade do código genético de C. albicans e revelam funções inesperadas da ambiguidade do código genético na evolução da diversidade genética e fenotípica.
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Birnbaum, David. "Altérations moléculaires dans l'adénocarcinome du pancréas." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5088.
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Le cancer du pancréas est un problème majeur de santé publique. Le mauvais pronostic de l'adénocarcinome du pancréas est lié à un diagnostic tardif, une progression rapide, et à une mauvaise réponse aux traitements médicaux disponibles. Une caractérisation complète des altérations génétiques moléculaires sont aujourd'hui nécessaires pour permettre une détection plus précoce et identifier/élaborer de nouvelles thérapies ciblées dans le traitement de l'ADK du pancréas. En utilisant la technique d'hybridation génomique comparative, nous avons étudié les altérations du génome de 39 ADK. Plusieurs pertes récurrentes ont été observées, ainsi que des gains de matériel génétique. A partir de ces résultats, nous avons voulu aller plus loin en identifiant les gènes qui pourraient avoir des conséquences au niveau transcriptomique. A partir de données publiques, nous avons comparé les profils d'expression d'ADK (n=419) et de pancréas normal (n=105). Parmi les gènes trouvés amplifiés et/ou gagnés par aCGH, 170 (48%) étaient surexprimés dans les ADK par rapport au tissus normal. Les principales voies de signalisation impliquées touchaient la régulation du cycle cellulaire, les voies TP53 et TGFß. Parmi les gènes délétés en aCGH, 141 (41%) étaient sous exprimés dans les ADK du pancréas par rapport au tissus normal et étaient essentiellement liés au « métabolome » de la cellule pancréatique. Enfin, nous avons identifié une dizaine de gènes dont l'expression pourrait être liée à la survie des patients. Certains de ces gènes pourraient être des candidats à tester en tant que biomarqueurs pronostic ou cibles pour le développement de nouvelles thérapeutiquesPancreatic adenocarcinoma (PDCA) is a major public health problem in France and worldwide. The inoperability and the poor prognosis of the PDCA are due to late diagnosis, rapid tumor progression (>80% of patients displayed metastases at diagnosis), early recurrences after resection, and poor response to available therapies. Innovative approaches and a comprehensive characterization of molecular genetic alterations are dearly needed to help develop techniques of early detection, identify new molecular targets and devise novel targeted-therapies (Hidalgo, 2010). Using high-resolution array-comparative genomic hybridization (aCGH), we studied the genome alterations of 39 fine-needle aspirations from PDCA. Recurrent losses were observed and comprised several known tumor suppressor genes. We identified frequent genetic gains. With this study, we decided to go one step further by identifying genes that might also be deregulated at the transcriptomic level. We started our analysis with a population of PDCA (n=419) versus normal pancreas (n = 105). Among the 352 genes found amplified and/or gained by aCGH, 170 (48%) were up regulated at the transcriptional level in PDCA compared to normal pancreatic tissues. Major pathways involved were cell cycle, TP53 and TGFß. Among the genes located in regions of losses, 141 (41%) were down regulated in PDCA compared to normal tissues. Furthermore, some genes were found related to a patients' survival With this study, we highlighted novels genes associated to PDCA oncogenesis. Some of those candidates should be further investigated as prognosis markers or as potential targets for new therapeutic approaches
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Statello, Luisa. "Specific Alterations of miRNA Transcriptome and Global Network Structure in Colorectal Cancer After Inhibition of MAPK/ERK Signaling Pathway." Doctoral thesis, Università di Catania, 2013. http://hdl.handle.net/10761/1343.
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Colorectal cancer (CRC) is one of the most frequent malignancies affecting western societies. Currently, the gold standard of CRC treatment is cetuximab, a monoclonal antibody, alone or in combination with chemotherapy. Not all patients positively respond to cetuximab: the analysis of KRAS mutational status at tumor site, a highly invasive analysis, is the only universally accepted genetic predictor for patient s response. However, some KRAS wild type patients, potential good responders, don t benefit from this therapy. To overcome these obstacles, research is focusing on the identification of new biomarkers detectable in circulating blood or other body fluids that can be used for diagnosis as well as for predicting the response to certain therapies. miRNAs, small RNA molecules involved in all aspects of cellular metabolism through regulation of gene expression, have been identified as new biomarkers for many diseases and cancers, including CRC. On the other hand, the scientific research is investigating on new molecules providing high specificity for the key players of the main cellular pathway affected in cancer. The main pathway involved in CRC is MAPK/ERK signaling pathway, which members are good targets for designing new specific inhibitors that could help to overcome the problems related to non-responsive patients to EGFR-targeted therapy. This thesis is focused on the relationship between the response to certain drugs and miRNA transcriptome changes in CRC human cellular models, based on KRAS mutational status. We profiled the expression of 667 miRNAs in 2 human CRC cell lines (Caco-2, KRAS wild type, and HCT-116, KRAS mutated), and 745 miRNAs in 3 CRC cell lines (Caco-2, HCT-116 and SW-620, another KRAS mutated cell line) after treatment with cetuximab and three specific inhibitors of MAPK pathway, respectively. Our aim was the identification of typical miRNA transcription profiles associated to cetuximab response, as well as the investigation on the global involvement of miRNAs within MAPK/ERK pathway. In the first analysis we identified substantially unique subsets of differentially expressed miRNAs in the sensitive cell line compared to the resistant one. Global network functional analysis on their targets suggested a role of these miRNAs in cancer related processes and identified hubs involved in EGFR internalization. In the second analysis we identified six differentially expressed miRNAs, that we have demonstrated to be involved in cell proliferation, migration, apoptosis, and to globally affect the regulation circuits centered on MAPK/ERK signaling. We evaluated the expression of the main candidate miRNAs identified in both studies in biopsies from CRC patients, previously categorized for their KRAS status: two miRNAs from the first study (miR-146b-3p and miR-486-5p) and four from the second (miR-92a-1*, miR-135b*, miR-372, miR-720) resulted highly expressed in biopsies from CRC patients than in normal controls. Moreover, the last four miRNAs are also overexpressed in CRC patients with mutated KRAS than in wild-type genotypes. The identification of miRNAs, which expression is linked to the efficacy of therapy, should help to predict the patients response to treatment and possibly lead to a better understanding of the molecular mechanisms of drug response. Our results contribute to deepen current knowledge on some features MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy. Data shown in this thesis were published in 2010 and 2012 (Ragusa M, Majorana A, Statello L, et al. Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment. Mol Cancer Ther. 2010 Dec; 9:3396-409; Ragusa M, Statello L, Maugeri M, et al. Specific alterations of the microRNA transcriptome and global network structure in colorectal cancer after treatment with MAPK/ERK inhibitors. J Mol Med (Berl). 2012 Jun 4).
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Liu, Xinhao. "Effects of Paternal Obesity on the Metabolic Profile of Offspring: Alterations in Gastrocnemius Muscle GLUT4 Trafficking and Mesenteric Adipose Tissue Transcriptome." Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou153453494204764.
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Barbier, Emeline. "Étude des mécanismes physiopathologiques impliqués dans la toxicité des particules ultrafines chez un modèle murin : une approche multi-organes." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS063.
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Bien qu'une diminution conséquente de la pollution atmosphérique soit constatée depuis les années 1990, cette dernière demeure un problème de santé publique majeur, à l'origine de plus de 4,2 millions de décès prématurés par an dans le monde. À l'heure actuelle, l'attention des experts se concentre sur les particules ultrafines (PM0,1 ou PUF) en raison de leur capacité à transloquer dans la circulation systémique pour atteindre les organes périphériques où elles seront alors susceptibles d'avoir un impact néfaste. Néanmoins, les connaissances en termes de mécanismes cellulaires et moléculaires impliqués dans la toxicité de ces particules restent encore très parcellaires et demeurent, le plus souvent, centrées sur leur cible principale qu'est le poumon. Ainsi, ce projet de thèse avait pour objectifs principaux d'apporter des éléments novateurs sur la toxicocinétique (i.e., distribution/persistance) et la toxicodynamique (i.e., mécanismes physiopathologiques, voies de signalisation associées) de PUF prélevées en milieu urbain, d'une part, et les effets organo-spécifiques des PUF et l'utilisation des miARN circulants comme indicateurs d'exposition chronique et/ou cumulées aux PUF dans un modèle murin, d'autre part. Afin de répondre à ces interrogations, des souris Balb/cJRj ont été exposées durant 3 mois à différentes doses de PUF prélevées dans la zone urbaine de Lille, puis des analyses ont été réalisés au sein de différents organes-cibles richement vascularisés, et par conséquent directement exposés aux PUF lors de leur phase de translocation et de distribution systémique. Les résultats obtenus ont démontré que, dans l'ensemble des organes cibles, le potentiel oxydant intrinsèque des PUF induisait indéniablement la production d'espèces pro-oxydantes et l'activation de défenses antioxydantes en quantité suffisante pour rétablir un état d'homéostasie redox mais ne parvenant pas, cependant, à éviter l'apparition d'une réponse inflammatoire au niveau pulmonaire, cardiaque et cérébral. Des approches transcriptomiques réalisés au sein des poumons, organes cibles présentant les effets délétères les plus marqués, ont suggéré la dérégulation de nombreuses voies de signalisation en relation avec les réponses oxydante et inflammatoire, qui constituent les mécanismes centraux de toxicité des PUF mais aussi avec des mécanismes de toxicité plus originaux tels que la dysfonction mitochondriale, la transition épithélio-mésenchymateuse et le remodelage tissulaire, dont la modulation a également été validée d'un point de vue fonctionnel. Ces données prometteuses pourraient à terme contribuer à une meilleure prise de décision quant à la réduction des émissions des PUF de même qu'à la réactualisation des normes réglementaires actuellement en vigueurAlthough there has been a significant reduction in air pollution since the 1990s, it remains a major public health problem, responsible for over 4.2 million premature deaths worldwide every year. At present, experts' attention is focused on ultrafine particles (PM0.1 or UFP) because of their ability to translocate into the systemic circulation and reach peripheral organs, where they are likely to have a harmful impact. Nevertheless, the knowledge of the cellular and molecular mechanisms involved in the toxicity of these particles is still very patchy, and most often remains focused on their main target, the lung. Thus, the main objectives of this thesis project were to provide innovative insights into the toxicokinetics (i.e., distribution/persistence) and toxicodynamics (i.e., pathophysiological mechanisms, associated cell signaling pathways) of UFP collected in urban environments, on the one hand, and the organospecific effects of UFP and the use of circulating miRNA as indicators of chronic and/or cumulative exposure to UFP in a mouse model, on the other hand. To answer these questions, Balb/cJRj mice were exposed for 3 months to various doses of UFP collected in the urban area of Lille, then analyzed in various target organs richly vascularized, and therefore directly exposed to UFP during their translocation and systemic distribution phase. The results showed that, in all target organs, the intrinsic oxidative potential of UFP undeniably induced the production of oxidative oxygen species and the activation of antioxidant defenses in sufficient quantities to restore a state of redox homeostasis, but were unable to prevent the onset of an inflammatory response in the lungs, heart and brain. Transcriptomic approaches carried out in the lungs, the target organ with the most marked deleterious effects, have suggested the deregulation of numerous signaling pathways in relation to oxidative and inflammatory responses, which constitute the central mechanisms of UFP toxicity, but also with more original toxicity mechanisms such as mitochondrial dysfunction, epithelial-mesenchymal transition and tissue remodeling, whose modulation has also been validated from a functional point of view. These promising data could ultimately contribute to better decision-making on the reduction of UFP emissions, as well as to the updating of current regulatory standards
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Crispatzu, Giuliano [Verfasser], Michael [Gutachter] Nothnagel, Bernd [Gutachter] Wollnik, Joachim [Gutachter] Krug, and Holger [Gutachter] Thiele. "Integrative approaches to high-throughput data in lymphoid leukemias (on transcriptomes, the whole-genome mutational landscape, flow cytometry and gene copy-number alterations) / Giuliano Crispatzu ; Gutachter: Michael Nothnagel, Bernd Wollnik, Joachim Krug, Holger Thiele." Köln : Universitäts- und Stadtbibliothek Köln, 2017. http://d-nb.info/1141904438/34.
Full textBooks on the topic "Transcriptomic alterations"
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Talib, S. H., and Talib Yusuf Abbas Hussain. Transcriptomics: New Approach to Study Genetic Alteration in T2DM. Generis Publishing, 2021.
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Bittner, Edward A., and Shawn P. Fagan. The host response to trauma and burns in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0304.
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Following severe traumatic injury, patients enter a state of immune dysregulation consisting of both exaggerated inflammation and immune suppression. Traditionally, the host response has been viewed as an early systemic inflammatory response syndrome (SIRS) followed temporally by a compensatory anti-inflammatory or immune-suppressive response syndrome (CARS). While this paradigm has been widely accepted across both medical and scientific fields, recent advances have challenged this concept. The Glue grant investigators recently characterized both the initial inflammatory response to injury and the dynamic evolving recovery process. They found: (1) severe injury produces a rapid (< 12 hours) genomic reprioritization in which 80% of the leukocyte transcriptome is altered; (2) similarities in gene expression patterns between different injuries reveal an apparently fundamental response to severe inflammatory stress, which is far more common than different; (3) alterations in the expression of classical inflammatory and anti-inflammatory as well as adaptive immunity genes occur simultaneously, not sequentially after severe injury; (4) the temporal nature of the current SIRS/CARS paradigm is not supported at the level of the leukocyte transcriptome. Complications are not associated with genomic evidence of a ‘second hit’ and differ only in the magnitude and duration of this genomic reprioritization. Furthermore, the delayed clinical recovery with organ injury is not associated with dramatic qualitative differences in the leukocyte transcriptome. Finally, poor correlation between human and rodent inflammatory genomic responses will alter how the host response is studied in the future.
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Vermeulen, Roel, Douglas A. Bell, Dean P. Jones, Montserrat Garcia-Closas, Avrum Spira, Teresa W. Wang, Martyn T. Smith, Qing Lan, and Nathaniel Rothman. Application of Biomarkers in Cancer Epidemiology. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190238667.003.0006.
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Advancements in OMICs are now enabling investigators to explore comprehensively the biological consequences of exogenous and endogenous exposures by detecting molecular signatures of exposure, early signs of adverse biological effects, preclinical disease, and molecularly defined cancer subtypes. These new technologies have proven invaluable for assembling a comprehensive portrait of human exposure, health, and disease. This includes hypothesis-driven biomarkers, as well as platforms that can agnostically analyze entire biologic processes and “compartments,” including the measurement of small molecules (metabolomics), DNA polymorphisms and rarer inherited variants (genomics), methylation and microRNA (epigenomics), chromosome-wide alterations, mRNA (transcriptomics), proteins (proteomics), and the microbiome (microbiomics). Although the implementation of these technologies in epidemiologic studies has already shown great promise, some challenges of particular importance must be addressed. Non-genetic OMIC markers vary over time due to both random variation and physiologic changes. Therefore, there is an urgent need for cohorts to collect repeat biological samples over time.
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Renner, Tanya, Tianying Lan, Kimberly M. Farr, Enrique Ibarra-Laclette, Luis Herrera-Estrella, Stephan C. Schuster, Mitsuyasu Hasebe, Kenji Fukushima, and Victor A. Albert. Carnivorous plant genomes. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198779841.003.0011.
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Carnivorous plant genome research has focused on members of the Lamiales and Oxalidales; the most complete sequences are for Utricularia gibba and Cephalotus follicularis. The size-limited U. gibba genome highlights the importance of small-scale tandem duplications, which likely play roles in this species’ carnivorous adaptation. Sequencing of the C. follicularis genome detected adaptive changes that may explain the evolution of traits associated with attraction, trapping, digestion, and absorption. Functional consequences of genes putatively missing in the U. gibba genome, yet present in other angiosperms, may have influenced the evolution of polyploidy, physiology, and a rootless Bauplan. Additional draft nuclear genomes and transcriptomes are available for carnivorous Caryophyllales, Ericales, Lamiales, and Poales, but are limited in quantity and quality. Chloroplast genomes of carnivorous Lentibulariaceae have revealed interesting patterns of gene loss, alterations in the proportion of repeat DNA, and plastome-wide increases in substitution rates.
Book chapters on the topic "Transcriptomic alterations"
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Saquib, Quaiser, Maqsood A. Siddiqui, Javed Ahmad, Sabiha M. Ansari, Mohammad Faisal, Rizwan Wahab, Abdulrahman A. Alatar, Abdulaziz A. Al-Khedhairy, and Javed Musarrat. "Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells." In Advances in Experimental Medicine and Biology, 163–74. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-72041-8_10.
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Watson, Geoffrey Alan, Kirsty Taylor, and Lillian L. Siu. "Innovation and Advances in Precision Medicine in Head and Neck Cancer." In Critical Issues in Head and Neck Oncology, 355–73. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-63234-2_24.
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AbstractThe clinical utility of precision medicine through molecular characterization of tumors has been demonstrated in some malignancies, especially in cases where oncogenic driver alterations are identified. Next generation sequencing data from thousands of patients with head and neck cancers have provided vast amounts of information about the genomic landscape of this disease. Thus far, only a limited number of genomic alterations have been druggable, such as NTRK gene rearrangements in salivary gland cancers (mainly mammary analogue secretory carcinoma), NOTCH mutations in adenoid cystic cancers, HRAS mutations in head and neck squamous cell cancers, and even a smaller number of these have reached regulatory approval status. In order to expand the scope of precision medicine in head and neck cancer, additional evaluation beyond genomics is necessary. For instance, there is increasing interest to perform transcriptomic profiling for target identification. Another advance is in the area of functional testing such as small interfering RNA and drug libraries on patient derived cell cultures. Liquid biopsies to detect specific tumor clones or subclones, or viral sequences such as HPV, are of great interest to enable non-invasive tracking of response or resistance to treatment. In addition, precision immuno-oncology is a tangible goal, with a growing body of knowledge on the interactions between the host immunity, the tumor and its microenvironment. Immuno-oncology combinations that are tailored to immunophenotypes of the host-tumor-microenvironment triad, personalized cancer vaccines, and adoptive cell therapies, among others, are in active development. Many therapeutic possibilities and opportunities lie ahead that ultimately will increase the reality of precision medicine in head and neck cancer.
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Juarez, Paul D., Darryl B. Hood, Min-ae Song, and Aramandla Ramesh. "Applying an Exposome-wide Association Study (ExWAS) Approach to Latino Cancer Disparities." In Advancing the Science of Cancer in Latinos, 17–32. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-14436-3_2.
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AbstractLatinos have higher incidence rates of cervical, gall bladder, liver, and gastric cancer, and higher mortality rates for six cancer sites than US Whites. This review chapter focuses on Latino cancer disparities, how the exposome can be applied to understanding Latino cancer disparities, and how environmental exposures lead to alterations in key biological pathways at the cellular, molecular, and system level, helping to explain the increased risk for population level cancer disparities among Latinos. An exposome-wide association study (ExWAS) approach is proposed as a novel conceptual framework to assess the role of multiple chemical and non-chemical exposures in the cause and progression of cancer among Latinos across the life course. Also discussed is how this strategy could be exploited by using biomarkers of susceptibility, exposure, and effect; and how a trans-omics approach, using recent advances in genomics, epigenomics, transcriptomics, metabolomics, proteomics, and lipidomics, could be used to deploy new biomarkers that serve both prognostic and diagnostic purposes. Also outlined are the knowledge gaps and scope for future studies in this area with implications for public health and policy interventions.
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Beckwith, Heather, and Douglas Yee. "Utilizing RNA-Seq to Define Phytochemical-Induced Alterations in Insulin and IGF-Regulated Transcriptomes." In Methods in Pharmacology and Toxicology, 189–204. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-9227-6_9.
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Cecilia Denninghoff, Valeria. "Molecular Pathology in the New Age of Personalized Medicine." In Histopathology and Liquid Biopsy [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94927.
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Personalized medicine is a new approach that allows the identification of patients that can benefit from targeted therapies because of the molecular characteristics of the tumors they present. The molecular profile of the tumor can be studied at the genomic (DNA), transcriptomic (RNA) or protein (protein) level. The next generation sequencing is a useful tool for the study of molecular profile from DNA/RNA. This tool requires molecular pathologists highly trained in pre-analytic processes, tumor area microdissection for tumor cell enrichment, methodology analysis and results. The in-depth study of molecular alterations in patients allows optimizing molecular diagnosis and selecting candidates for receive novel treatments against specific molecular targets. These patients are expected to benefit from multidisciplinary approach and learning. The aim of this chapter is to show the implications of molecular pathology in personalized medicine with an actual approach from the methodological limitations of formalin-fixed paraffin embedded (FFPE) tissues and their pre-analytical conditions.
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Vreugdenhil, Erno, and Nicole Datson. "Studying gene expression profiles in specialized brain regions by microSAGE." In Differential Display, 159–80. Oxford University PressOxford, 2000. http://dx.doi.org/10.1093/oso/9780199637584.003.0009.
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Abstract The human genome is thought to contain 100 000 genes of which a subset of approximately 15 000 to 20 000 genes is expressed in an individual cell. The set of genes expressed and the stoichiometry of the resulting messenger RNAs, together called a transcriptome, determine the phenotype of a cell, tissue, and whole organism. It is generally accepted that a transcriptome is largely determined by an interplay of hereditary and environmental factors. For example, in the CNS, a challenge from the environment, e.g. a learning or a traumatic experience may lead to an alteration of the transcriptome of target neurons. Thus, transcriptome analysis and subsequent transcriptome comparisons may reveal novel insights in the molecular mechanisms underlying complex processes such learning and memory formation.
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Filatova, Elena, Maria Shadrina, Petr Slominsky, and Svetlana Limborsk. "Analysis of Transcriptome Alterations in Parkinson’s Disease." In Etiology and Pathophysiology of Parkinson's Disease. InTech, 2011. http://dx.doi.org/10.5772/21070.
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Hassan, Muhammad Jawad, Muhammad Faheem, and Sabba Mehmood. "Emerging OMICS and Genetic Disease." In Omics Technologies for Clinical Diagnosis and Gene Therapy: Medical Applications in Human Genetics, 93–113. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815079517122010010.
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Multiomics also described as integrative omics is an analytical approach that combines data from multiple ‘omics’ approaches including genomics, transcriptomics, proteomics, metabolomics, epigenomics, metagenomics and Meta transcriptomics to answer the complex biological processes involved in rare genetic disorders. This omics approach is particularly helpful since it identifies biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the various types of cells to better understand and categorize the Mendelian and non- Mendelian forms of rare diseases. As compared to studies of a single omics type, multi-omics offers the opportunity to understand the flow of information that underlies the disease. A range of omics software and databases, for example WikiPathways, MixOmics, MONGKIE, GalaxyP, GalaxyM, CrossPlatform Commander, and iCluster are used for multi-omics data exploration and integration in rare disease analysis. Recent advances in the field of genetics and translational research have opened new treatment avenues for patients. The innovation in the next generation sequencing and RNA sequencing has improved the ability from diagnostics to detection of molecular alterations like gene mutations in specific disease types. In this chapter, we provide an overview of such omics technologies and focus on methods for their integration across multiple omics layers. The scrupulous understanding of rare genetic disorders and their treatment at the molecular level led to the concept of a personalized approach, which is one of the most significant advancements in modern research which enable researchers to better comprehend the flow of knowledge which underpins genetic diseases.
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Eltanahy, Eladl, and Aya Torky. "Integrated Omics and Mutation in Algae." In Handbook of Research on Algae as a Sustainable Solution for Food, Energy, and the Environment, 109–39. IGI Global, 2022. http://dx.doi.org/10.4018/978-1-6684-2438-4.ch005.
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Algae importance is spectacularly increasing in many biotechnological applications, such as human food, animal feed, biofuels, bioplastics, bioremediation, pharmaceuticals, and cosmetics. With the widespread use of “omics” technologies over the past two decades, recent advanced research attempts to understand the pathways of the promising algae species by whole genomes sequencing (genomics) and revealing lipid pathways (lipidomics), microarray to study all RNA transcripts (transcriptomics), all protein sets produced by the algal cell (proteomics). DNA alteration as classical mutagenesis caused a random mutation such as ethyl methane-sulfonate as chemical mutagenic and ultraviolet radiation as a physical mutagenic. On the other hand, the CRISPR-Cas9 modern technique is used to genetically engineer a protein with maximum editing efficiency. Incorporating omics and mutations techniques helps to thoroughly understand the systems biology of algae in the new era called integrated omics.
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Machlowska, Julita, and Ryszard Maciejewski. "Gastric Cancer in the Next-Generation Sequencing Era: Diagnostic and Therapeutic Strategies." In Molecular Diagnostics of Cancer [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.1002517.
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Gastric cancer (GC) is one of the most common malignancies and the fourth major cause of cancer-related deaths worldwide. There is growing interest in the role of genetic and epigenetic changes in the development of the disease. Next-generation sequencing (NGS) studies have identified candidate cancer-driving genes in the GC. Whole transcriptome sequencing and whole-genome sequencing analysis is also important methodology in discovering novel changes in GC. Importantly, cancer epigenetics has opened the way to reveal cancer-related genes in epigenetic machinery, including DNA methylation, nucleosome positioning, noncoding RNAs, and microRNAs, as well as histone modifications. The latest molecular research on GC may be a new diagnostic and therapeutic strategy in clinical practice. In this review, we will focus on recent advances in the description of the molecular pathogenesis of gastric cancer, underlying the use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
Conference papers on the topic "Transcriptomic alterations"
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Collar, Giovanna Carello, Marco Antônio De Bastiani, and Eduardo R. Zimmer. "HUNTINGTON’S DISEASE AND EARLYONSET ALZHEIMER’S DISEASE SHARE A TRANSCRIPTOMIC SIGNATURE." In XIII Meeting of Researchers on Alzheimer's Disease and Related Disorders. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1980-5764.rpda082.
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Background: Neurodegenerative diseases share progressive loss of neurons and protein misfolding, which ultimately culminates in dementia; many diseases have been identified as causes of early-onset dementia (< 65 years of age) such as Huntington’s disease (HD) and early-onset Alzheimer’s disease (EOAD). Importantly, disease-specific genetic mutations have already been identified for HD and EOAD. Thus, one could suggest that the molecular link between these diseases may arise from alterations at the transcriptomic level, which is yet to be determined. Objective: We aimed at identifying transcriptome similarities between HD and EOAD. Methods: We collected data of the postmortem cerebral cortex from 1 HD and 6 AD microarray studies in the Gene Expression Omnibus. Of note, only subjects with age at death under 65 were selected (HD: n = 158, controls: n = 158; EOAD: n = 65, controls: n = 266). Differential expression and functional enrichment analyses were performed. Results: We identified 1,260 differentially expressed genes and 675 enriched gene ontology terms between HD and EOAD. Conclusion: Our results demonstrate a transcriptomic signature shared by HD and EOAD. Unveiling the similarities between these diseases at the transcriptomic level could advance our knowledge about pathogenesis and may help to develop therapeutic strategies targeting early-onset dementias.
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Davidson, Natalie R., Alvis Brazma, Angela N. Brooks, Claudia Calabrese, Nuno A. Fonseca, Jonathan Goke, Yao He, et al. "Abstract 389: Integrating diverse transcriptomic alterations to identify cancer-relevant genes." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-389.
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Wei, Jun S., Andrew S. Brohl, Sivasish Sindiri, David Milewski, Young K. Song, Sushma Nagaraj, Vineela Gangalapudi, Xinyu Wen, Marc Ladanyi, and Javed Khan. "Abstract 3445: Immuno-transcriptomic profiling identifies actionable genomic alterations in pediatric solid malignancies." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-3445.
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Griffith, Obi L., Yiing Lin, Malachi Griffith, Jasreet Hundal, Allison Regier, Robert Fulton, Elizabeth M. Brunt, Richard K. Wilson, William Chapman, and Elaine R. Mardis. "Abstract 5181: Genomic and transcriptomic somatic alterations of hepatocellular carcinoma in non-cirrhotic livers." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-5181.
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Pinatti, Lisa M., Hana Sinha, Chad Brenner, Heather M. Walline, and Thomas E. Carey. "Abstract 4896: Transcriptomic alterations by HPV-human fusion transcripts in HPV+ HNSCC cell lines." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-4896.
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Papadodima, Olga, Aristotelis Chatziioanou, Allan Sirsjo, and Fragiskos N. Kolisis. "Bioinformatic transcriptomic analysis of ApoE deficient mice suggests Alterations in atherosclerosis related molecular mechanisms." In 2010 10th IEEE International Conference on Information Technology and Applications in Biomedicine (ITAB 2010). IEEE, 2010. http://dx.doi.org/10.1109/itab.2010.5687785.
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Cheng, Hui, Riyue Bao, Carter Van Waes, and Vassiliki Saloura. "Abstract 5178: Genomic and transcriptomic alterations of chromatin factors in head and neck cancer." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-5178.
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Cheng, Hui, Riyue Bao, Carter Van Waes, and Vassiliki Saloura. "Abstract 5178: Genomic and transcriptomic alterations of chromatin factors in head and neck cancer." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-5178.
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Liu, Zhigang, Kaixing Le, and Nick Powell. "P78 Deciphering the transcriptomic and metabolic alterations in a microbiota-dependent model of ulcerative colitis." In BSG LIVE’23, 19–22 June, ACC Liverpool. BMJ Publishing Group Ltd and British Society of Gastroenterology, 2023. http://dx.doi.org/10.1136/gutjnl-2023-bsg.150.
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Korkut, Anil, Sobia Zaidi, Rupa Kanchi, Ashton C. Berger, Gordon Robertson, Lawrence N. Kwong, Mike Datto, et al. "Abstract 3413: A pan-cancer atlas of genomic, epigenomic and transcriptomic alterations in the TGF-β pathway." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-3413.
Full textReports on the topic "Transcriptomic alterations"
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Li, Li, Joseph Burger, Nurit Katzir, Yaakov Tadmor, Ari Schaffer, and Zhangjun Fei. Characterization of the Or regulatory network in melon for carotenoid biofortification in food crops. United States Department of Agriculture, April 2015. http://dx.doi.org/10.32747/2015.7594408.bard.
Full textAbstract:
The general goals of the BARD research grant US-4423-11 are to understand how Or regulates carotenoid accumulation and to reveal novel strategies for breeding agricultural crops with enhanced β-carotene level. The original objectives are: 1) to identify the genes and proteins in the Or regulatory network in melon; 2) to genetically and molecularly characterize the candidate genes; and 3) to define genetic and functional allelic variation of these genes in a representative germplasm collection of the C. melo species. Or was found by the US group to causes provitamin A accumulation in chromoplasts in cauliflower. Preliminary genetic study from the Israeli group revealed that the melon Or gene (CmOr) completely co-segregated with fruit flesh color in a segregating mapping population and in a wide melon germplasm collection, which set the stage for the funded research. Major conclusions and achievements include: 1). CmOris proved to be the gene that controls melon fruit flesh color and represents the previously described gflocus in melon. 2). Genetic and molecular analyses of CmOridentify and confirm a single SNP that is responsible for the orange and non-orange phenotypes in melon fruit. 3). Alteration of the evolutionarily conserved arginine in an OR protein to both histidine or alanine greatly enhances its ability to promote carotenoid accumulation. 4). OR promotes massive carotenoid accumulation due to its dual functions in regulating both chromoplast biogenesis and carotenoid biosynthesis. 5). A bulk segregant transcriptome (BSRseq) analysis identifies a list of genes associated with the CmOrregulatory network. 6). BSRseq is proved to be an effective approach for gene discovery. 7). Screening of an EMS mutation library identifies a low β mutant, which contains low level of carotenoids due to a mutation in CmOrto produce a truncated form of OR protein. 8). low β exhibits lower germination rate and slow growth under salt stress condition. 9). Postharvest storage of fruit enhances carotenoid accumulation, which is associated with chromoplast development. Our research uncovers the molecular mechanisms underlying the Or-regulated high level of carotenoid accumulation via regulating carotenoidbiosynthetic capacity and storage sink strength. The findings provide mechanistic insights into how carotenoid accumulation is controlled in plants. Our research also provides general and reliable molecular markers for melon-breeding programs to select orange varieties, and offers effective genetic tools for pro-vitamin A enrichment in other important crops via the rapidly developed genome editing technology. The newly discovered low β mutant could lead to a better understanding of the Or gene function and its association with stress response, which may explain the high conservation of the Or gene among various plant species.
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Jander, Georg, and Daniel Chamovitz. Investigation of growth regulation by maize benzoxazinoid breakdown products. United States Department of Agriculture, January 2015. http://dx.doi.org/10.32747/2015.7600031.bard.
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Introduction Previous research had suggested that benzoxazinoids, a class of defensive metabolites found in maize, wheat, rye, and wild barley, are not only direct insect deterrents, but also influence other areas of plant metabolism. In particular, the benzoxazinoid 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxa- zin-3(4H)- one (DIMBOA) was implicated in: (i) altering plant growth by interfering with auxin signaling, and (ii) leading to the induction of gene expression changes and secondary plant defense responses. The overall goal of this proposal was to identify mechanisms by which benzoxazinoids influence other aspects of plant growth and defense. Specifically, the following hypotheses were proposed to be tested as part of an approved BARD proposal: Benzoxazinoid breakdown products directly interfere with auxin perception Global changes in maize and barley gene expression are induced by benzoxazinoid activation. There is natural variation in the maize photomorphogenic response to benzoxazinoids. Although the initial proposal included experiments with both maize and barley, there were some technical difficulties with the proposed transgenic barley experiments and most of the experimental results were generated with maize. Summary of major findings Previous research by other labs, involving both maize and other plant species, had suggested that DIMBOA alters plant growth by interfering with auxin signaling. However, experiments conducted in both the Chamovitz and the Jander labs using Arabidopsis and maize, respectively, were unable to confirm previously published reports of exogenously added DIMBOA effects on auxin signaling. Nevertheless, analysis of bx1 and bx2 maize mutant lines, which have almost no detectable benzoxazinoids, showed altered responses to blue light signaling. Transcriptomic analysis of maize mutant lines, variation in inbred lines, and responses to exogenously added DIMBOA showed alteration in the transcription of a blue light receptor, which is required for plant growth responses. This finding provides a novel mechanistic explanation of the trade-off between growth and defense that is often observed in plants. Experiments by the Jander lab and others had demonstrated that DIMBOA not only has direct toxicity against insect pests and microbial pathogens, but also induces the formation of callose in both maize and wheat. In the current project, non-targeted metabolomic assays of wildtype maize and mutants with defects in benzoxazinoid biosynthesis were used to identify unrelated metabolites that are regulated in a benzoxazinoid-dependent manner. Further investigation identified a subset of these DIMBOA-responsive compounds as catechol, as well as its glycosylated and acetylated derivatives. Analysis of co-expression data identified indole-3-glycerol phosphate synthase (IGPS) as a possible regulator of benzoxazinoid biosynthesis in maize. In the current project, enzymatic activity of three predicted maize IGPS genes was confirmed by heterologous expression. Transposon knockout mutations confirmed the function of the maize genes in benzoxazinoid biosynthesis. Sub-cellular localization studies showed that the three maize IGPS proteins are co-localized in the plastids, together with BX1 and BX2, two previously known enzymes of the benzoxazinoid biosynthesis pathway. Implications Benzoxazinoids are among the most abundant and effective defensive metabolites in maize, wheat, and rye. Although there is considerable with-in species variation in benzoxazinoid content, very little is known about the regulation of this variation and the specific effects on plant growth and defense. The results of this research provide further insight into the complex functions of maize benzoxazinoids, which are not only toxic to pests and pathogens, but also regulate plant growth and other defense responses. Knowledge gained through the current project will make it possible to engineer benzoxazinoid biosynthesis in a more targeted manner to produce pest-tolerant crops without negative effects on growth and yield.
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Cohen, Yuval, Christopher A. Cullis, and Uri Lavi. Molecular Analyses of Soma-clonal Variation in Date Palm and Banana for Early Identification and Control of Off-types Generation. United States Department of Agriculture, October 2010. http://dx.doi.org/10.32747/2010.7592124.bard.
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Date palm (Phoenix dactylifera L.) is the major fruit tree grown in arid areas in the Middle East and North Africa. In the last century, dates were introduced to new regions including the USA. Date palms are traditionally propagated through offshoots. Expansion of modern date palm groves led to the development of Tissue Culture propagation methods that generate a large number of homogenous plants, have no seasonal effect on plant source and provide tools to fight the expansion of date pests and diseases. The disadvantage of this procedure is the occurrence of off-type trees which differ from the original cultivar. In the present project we focused on two of the most common date palm off-types: (1) trees with reduced fruit setting, in which most of the flowers turn into three-carpel parthenocarpic fruits. In a severe form, multi-carpel flowers and fruitlets (with up to six or eight carpels instead of the normal three-carpel flowers) are also formed. (2) dwarf trees, having fewer and shorter leaves, very short trunk and are not bearing fruits at their expected age, compared to the normal trees. Similar off-types occur in other crop species propagated by tissue culture, like banana (mainly dwarf plants) or oil palm (with a common 'Mantled' phenotype with reduced fruit setting and occurrence of supernumerary carpels). Some off-types can only be detected several years after planting in the fields. Therefore, efficient methods for prevention of the generation of off-types, as well as methods for their detection and early removal, are required for date palms, as well as for other tissue culture propagated crops. This research is aimed at the understanding of the mechanisms by which off-types are generated, and developing markers for their early identification. Several molecular and genomic approaches were applied. Using Methylation Sensitive AFLP and bisulfite sequencing, we detected changes in DNA methylation patterns occurring in off-types. We isolated and compared the sequence and expression of candidate genes, genes related to vegetative growth and dwarfism and genes related to flower development. While no sequence variation were detected, changes in gene expression, associated with the severity of the "fruit set" phenotype were detected in two genes - PdDEF (Ortholog of rice SPW1, and AP3 B type MADS box gene), and PdDIF (a defensin gene, highly homologous to the oil palm gene EGAD). We applied transcriptomic analyses, using high throughput sequencing, to identify genes differentially expressed in the "palm heart" (the apical meristem and the region of embryonic leaves) of dwarf vs. normal trees. Among the differentially expressed genes we identified genes related to hormonal biosynthesis, perception and regulation, genes related to cell expansion, and genes related to DNA methylation. Using Representation Difference Analyses, we detected changes in the genomes of off-type trees, mainly chloroplast-derived sequences that were incorporated in the nuclear genome and sequences of transposable elements. Sequences previously identified as differing between normal and off-type trees of oil palms or banana, successfully identified variation among date palm off-types, suggesting that these represent highly labile regions of monocot genomes. The data indicate that the date palm genome, similarly to genomes of other monocot crops as oil palm and banana, is quite unstable when cells pass through a cycle of tissue culture and regeneration. Changes in DNA sequences, translocation of DNA fragments and alteration of methylation patterns occur. Consequently, patterns of gene expression are changed, resulting in abnormal phenotypes. The data can be useful for future development of tools for early identification of off-type as well as for better understanding the phenomenon of somaclonal variation during propagation in vitro.