Colorectal Cancer Concurrent Gene Signature Based on Coherent Patterns between Genomic and Transcriptional Alterations
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PROVIDER: PRJNA812057 | ENA |
REPOSITORIES: ENA
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Project description:The aim of the study was to enhance colorectal cancer prognostication by integrating single nucleotide polymorphism (SNP) and gene expression (GE) microarrays for genomic and transcriptional alteration detection; genes with concurrent gains and losses were used to develop a prognostic signature.
2022-03-15 | GSE197802 | GEO
Project description:BackgroundThe aim of the study was to enhance colorectal cancer prognostication by integrating single nucleotide polymorphism (SNP) and gene expression (GE) microarrays for genomic and transcriptional alteration detection; genes with concurrent gains and losses were used to develop a prognostic signature.MethodsThe discovery dataset comprised 32 Taiwanese colorectal cancer patients, of which 31 were assayed for GE and copy number variations (CNVs) with Illumina Human HT-12 BeadChip v4.0 and Omni 25 BeadChip v1.1. Concurrent gains and losses were declared if coherent manners were observed between GE and SNP arrays. Concurrent genes were also identified in The Cancer Genome Atlas Project (TCGA) as the secondary discovery dataset (n = 345).ResultsThe "universal" concurrent genes, which were the combination of z-transformed correlation coefficients, contained 4022 genes. Candidate genes were evaluated within each of the 10 public domain microarray datasets, and 1655 (2000 probe sets) were prognostic in at least one study. Consensus across all datasets was used to build a risk predictive model, while distinct relapse-free/overall survival patterns between defined risk groups were observed among four out of five training datasets. The predictive accuracy of recurrence, metastasis, or death was between 61 and 86% (cross-validation area under the receiver operating characteristic (ROC) curve: 0.548-0.833) from five independent validation studies.ConclusionThe colorectal cancer concurrent gene signature is prognostic in terms of recurrence, metastasis, or mortality among 1746 patients. Genes with coherent patterns between genomic and transcriptional contexts are more likely to provide prognostication for colorectal cancer.
| S-EPMC9150289 | biostudies-literature
Project description:Genome-wide alterations of uracil distribution patterns
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Project description:Genomic DNA folds into complex configurations that produce particular local and globalstructures thought to profoundly impact genome function. To understand the dynamic nature ofthis relationship, we investigated the extent of host chromatin structural and functional changesin response to a viral agent. We performed comprehensive assessments of host architecture (Hi-C), accessibility (ATAC-seq), and gene expression (RNA-seq) in a paired manner in response toattenuated vaccinia (smallpox) virus. Over time, infection significantly increased long-rangeintra-chromosomal interactions and decreased chromatin accessibility. Fine-scale accessibilitychanges were independent of broad-scale chromatin compartment exchange, which increased (upto 12% of the genome) over time, underscoring potential independent mechanisms for global andlocal chromatin reorganization. The majority of differentially expressed genes, including thosedownregulated in immune responses, had concurrent alterations in local accessibility and loopdomain restructuring. Increased B compartmentalization, intra-chromosomal interactions, anddecreased inter-chromosomal interactions and chromatin accessibility together indicate thatinfection converts the host genome into a more condensed state with nearly equal bidirectionaldifferential gene expression. These changes in host chromatin features may have implications fordeveloping efficacious anti-viral countermeasures. Overall, our empirical data provides evidenceof orchestrated concurrent alterations in chromatin architecture, accessibility, and geneexpression in response to infection, further reinforcing the notion of coordinated structurefunctiondynamics of the genome.
2024-05-07 | GSE248048 | GEO
Project description:Genomic DNA folds into complex configurations that produce particular local and globalstructures thought to profoundly impact genome function. To understand the dynamic nature ofthis relationship, we investigated the extent of host chromatin structural and functional changesin response to a viral agent. We performed comprehensive assessments of host architecture (Hi-C), accessibility (ATAC-seq), and gene expression (RNA-seq) in a paired manner in response toattenuated vaccinia (smallpox) virus. Over time, infection significantly increased long-rangeintra-chromosomal interactions and decreased chromatin accessibility. Fine-scale accessibilitychanges were independent of broad-scale chromatin compartment exchange, which increased (upto 12% of the genome) over time, underscoring potential independent mechanisms for global andlocal chromatin reorganization. The majority of differentially expressed genes, including thosedownregulated in immune responses, had concurrent alterations in local accessibility and loopdomain restructuring. Increased B compartmentalization, intra-chromosomal interactions, anddecreased inter-chromosomal interactions and chromatin accessibility together indicate thatinfection converts the host genome into a more condensed state with nearly equal bidirectionaldifferential gene expression. These changes in host chromatin features may have implications fordeveloping efficacious anti-viral countermeasures. Overall, our empirical data provides evidenceof orchestrated concurrent alterations in chromatin architecture, accessibility, and geneexpression in response to infection, further reinforcing the notion of coordinated structurefunctiondynamics of the genome.
2024-05-11 | GSE248050 | GEO
Project description:Genomic DNA folds into complex configurations that produce particular local and globalstructures thought to profoundly impact genome function. To understand the dynamic nature ofthis relationship, we investigated the extent of host chromatin structural and functional changesin response to a viral agent. We performed comprehensive assessments of host architecture (Hi-C), accessibility (ATAC-seq), and gene expression (RNA-seq) in a paired manner in response toattenuated vaccinia (smallpox) virus. Over time, infection significantly increased long-rangeintra-chromosomal interactions and decreased chromatin accessibility. Fine-scale accessibilitychanges were independent of broad-scale chromatin compartment exchange, which increased (upto 12% of the genome) over time, underscoring potential independent mechanisms for global andlocal chromatin reorganization. The majority of differentially expressed genes, including thosedownregulated in immune responses, had concurrent alterations in local accessibility and loopdomain restructuring. Increased B compartmentalization, intra-chromosomal interactions, anddecreased inter-chromosomal interactions and chromatin accessibility together indicate thatinfection converts the host genome into a more condensed state with nearly equal bidirectionaldifferential gene expression. These changes in host chromatin features may have implications fordeveloping efficacious anti-viral countermeasures. Overall, our empirical data provides evidenceof orchestrated concurrent alterations in chromatin architecture, accessibility, and geneexpression in response to infection, further reinforcing the notion of coordinated structurefunctiondynamics of the genome.
2024-05-11 | GSE248049 | GEO
Project description:High-throughput genomic studies have identified thousands of genetic alterations in colorectal cancer (CRC). Distinguishing driver from passenger mutations is critical for developing rational therapeutic strategies. Because only a few transcriptional subtypes exist in previously studied tumor types, we hypothesize that highly heterogeneous genomic alterations may converge to a limited number of distinct mechanisms that drive unique gene expression patterns in different transcriptional subtypes. In this study, we defined transcriptional subtypes for CRC and identified driver networks/pathways for each subtype, respectively. Applying consensus clustering to a patient cohort with 1173 samples identified three transcriptional subtypes, which were validated in an independent cohort with 485 samples. The three subtypes were characterized by different transcriptional programs related to normal adult colon, early colon embryonic development, and epithelial mesenchymal transition, respectively. They also showed statistically different clinical outcomes. For each subtype, we mapped somatic mutation and copy number variation data onto an integrated signaling network and identified subtype-specific driver networks using a random walk-based strategy. We found that genomic alterations in the Wnt signaling pathway were common among all three subtypes; however, unique combinations of pathway alterations including Wnt, VEGF, Notch and TGF-beta drove distinct molecular and clinical phenotypes in different CRC subtypes. Our results provide a coherent and integrated picture of human CRC that links genomic alterations to molecular and clinical consequences, and which provides insights for the development of personalized therapeutic strategies for different CRC subtypes. To characterize the embryonic development of colon, we conducted a time course microarray study using the inbred C57BL/6 (Jackson Laboratories, Bar Harbor, ME) mice. Seven samples corresponding to the mouse colonic development from E13.5 to E18.5 and adult (eight week post-natal) were collected. RNA samples were submitted to the Vanderbilt Functional Genomics Shared Resource (FSGR, http://array.mc.vanderbilt.edu), where RNA was hybridized to the Affymetrix Mouse Genome 430 2.0 GeneChip Expression Arrays (Santa Clara, CA) according to manufacturer’s instructions. The RMA algorithm was used for data normalization. Mouse gene symbols were mapped to human gene symbols by the Human and Mouse Orthology list available from the Mouse Genome Informatics (http://www.informatics.jax.org/).
2013-12-22 | E-GEOD-38831 | biostudies-arrayexpress
Project description:High-throughput genomic studies have identified thousands of genetic alterations in colorectal cancer (CRC). Distinguishing driver from passenger mutations is critical for developing rational therapeutic strategies. Because only a few transcriptional subtypes exist in previously studied tumor types, we hypothesize that highly heterogeneous genomic alterations may converge to a limited number of distinct mechanisms that drive unique gene expression patterns in different transcriptional subtypes. In this study, we defined transcriptional subtypes for CRC and identified driver networks/pathways for each subtype, respectively. Applying consensus clustering to a patient cohort with 1173 samples identified three transcriptional subtypes, which were validated in an independent cohort with 485 samples. The three subtypes were characterized by different transcriptional programs related to normal adult colon, early colon embryonic development, and epithelial mesenchymal transition, respectively. They also showed statistically different clinical outcomes. For each subtype, we mapped somatic mutation and copy number variation data onto an integrated signaling network and identified subtype-specific driver networks using a random walk-based strategy. We found that genomic alterations in the Wnt signaling pathway were common among all three subtypes; however, unique combinations of pathway alterations including Wnt, VEGF, Notch and TGF-beta drove distinct molecular and clinical phenotypes in different CRC subtypes. Our results provide a coherent and integrated picture of human CRC that links genomic alterations to molecular and clinical consequences, and which provides insights for the development of personalized therapeutic strategies for different CRC subtypes.
2013-12-22 | GSE38831 | GEO
Project description:Gene expression profiles of 70 patients presenting with concurrent colorectal adenomas and colorectal tumors were obtained using Affymetrix U133+ arrays.
2018-12-01 | GSE117606 | GEO
Project description:Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.
2023-04-01 | GSE137832 | GEO