Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profiles
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ABSTRACT:
PROVIDER: PRJNA248538 | ENA |
REPOSITORIES: ENA
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Project description:Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profiles
| PRJNA248539 | ENA
Project description:STAGING: Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profiles
| PRJNA248537 | ENA
Project description:STAGING: Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profiles
| PRJNA248536 | ENA
Project description:<p>The Multiple Myeloma Research Foundation (MMRF) CoMMpass (Relating <u>C</u>linical <u>O</u>utcomes in <u>MM</u> to <u>P</u>ersonal <u>Ass</u>essment of Genetic Profile) trial (NCT01454297) is a longitudinal observation study of 1000 newly diagnosed myeloma patients receiving various standard approved treatments that aim at collecting tissue samples, genetic information, Quality of Life (QoL) and various disease and clinical outcomes over 10 years.</p>
| phs000748 | dbGaP
Project description:Personal Neoantigen Cancer Vaccines
| PRJNA401959 | ENA
Project description:Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our study aimed to investigate the dynamics of personal methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration. 52 plasma samples from 9 patients with mPCa were collected, longitudinally, over 13-21 months. After cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip and analysed using the minfi software. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify and validate ctDNA differentially methylated genes (DMGs). Personal cfDNA global methylation patterns were temporally stable throughout disease course. A proportion of analysed CpG sites presented a dynamic temporal pattern that was consistent with clinical events, such as therapy administration, and were prominently associated with immune response pathways. Study of ctDNA identified >2,000 DMGs with dynamic methylation patterns. We concluded that longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with the occurrence of specific clinical events, thus highlighting the potential of using liquid biopsies to study PCa progression.
2021-09-01 | GSE157273 | GEO
Project description:Organisms can gain information about their environment from their ancestors, their parents, or their own personal experience. “Cue integration” models often start with the simplifying assumption that information from different sources is additive. Here, we test key assumptions and predictions of cue integration theory at both the phenotypic and molecular level in threespined sticklebacks (Gasterosteus aculeatus). We show that regardless of whether cues about predation risk were provided by their father or acquired through personal experience, sticklebacks produced the same set of predator-adapted phenotypes. Moreover, there were nonadditive effects of personal and paternal experience: animals that received cues from both sources resembled animals that received cues from a single source. A similar pattern was detected at the molecular level: there was a core set of genes that were differentially expressed in the brains of offspring regardless of whether risk was experienced by their father, themselves or both. These results provide strong support for cue integration theory because they show that cues provided by parents and personal experience are comparable at both the phenotypic and molecular level, and draw attention to the importance of nonadditive responses to multiple cues.
2018-06-13 | GSE113548 | GEO
Project description:An overall goal of functional genomics has been to measure the impact of variants on molecular endophenotypes (e.g. gene expression levels or the degree of TF binding) and relate this to organismal traits and disease phenotypes. However, all the experiments to date have been described relative to a generic reference genome, significantly hobbling their interpretation. Here, we describe a strategy for finding significant relationships between disease variation and genomic annotation via personal functional genomics, by performing personal genome sequencing and paired functional genomics experiments, on the same individual.
2024-05-22 | PXD022787 | Pride
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tag (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD043580 | Pride
Project description:Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, multiple myeloma remains incurable and better risk stratification as well as new therapies are therefore highly needed. The proteome of multiple myeloma has not been systematically assessed before and holds the potential to uncover additional insight into disease biology and improved prognostic models. Here, we provide a comprehensive multi-omics analysis including deep tandem mass tags (TMT)-based quantitative global (phospho)proteomics, RNA sequencing and nanopore DNA sequencing of 138 primary patient-derived plasma cell malignancies encompassing treatment-naive multiple myeloma patients treated in clinical trials, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance (MGUS), as well as healthy controls. We found that the (phospho)proteome of malignant plasma cells is highly deregulated as compared to healthy plasma cells and is both defined by chromosomal alterations and extensive post-transcriptional regulation. A protein signature was identified that is associated with aggressive disease and more predictive for outcome than cytogenetic-based risk assessment in newly diagnosed multiple myeloma. Integration with functional genetics and single-cell sequencing revealed generally and genetic subtype-specific deregulated proteins and pathways in plasma cell malignancies that include novel potential targets for (immuno)therapies. These findings provide new insights in the biology of multiple myeloma and will be a unique resource for investigating new therapeutic approaches.
2024-07-09 | PXD038437 | Pride