Stochastic Modeling of the Relationship between Copy Number and Gene Expression Based on Transcriptional Logic

2012 ◽  
Vol 59 (1) ◽  
pp. 272-280 ◽  
Author(s):  
Fang-Han Hsu ◽  
Erchin Serpedin ◽  
Yidong Chen ◽  
Edward R. Dougherty
Keyword(s):  
Gene Expression ◽  
Stochastic Modeling ◽  
Copy Number ◽  
The Relationship

scholarly journals Copy number variation is highly correlated with differential gene expression: a pan-cancer study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xin Shao ◽  
Ning Lv ◽  
Jie Liao ◽  
Jinbo Long ◽  
Rui Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Copy Number Variation ◽  
Differential Gene Expression ◽  
Copy Number ◽  
Close Correlation ◽  
Number Variation ◽  
Cancer Types ◽  
Differential Gene ◽  
The Relationship

Abstract Background Cancer is a heterogeneous disease with many genetic variations. Lines of evidence have shown copy number variations (CNVs) of certain genes are involved in development and progression of many cancers through the alterations of their gene expression levels on individual or several cancer types. However, it is not quite clear whether the correlation will be a general phenomenon across multiple cancer types. Methods In this study we applied a bioinformatics approach integrating CNV and differential gene expression mathematically across 1025 cell lines and 9159 patient samples to detect their potential relationship. Results Our results showed there is a close correlation between CNV and differential gene expression and the copy number displayed a positive linear influence on gene expression for the majority of genes, indicating that genetic variation generated a direct effect on gene transcriptional level. Another independent dataset is utilized to revalidate the relationship between copy number and expression level. Further analysis show genes with general positive linear influence on gene expression are clustered in certain disease-related pathways, which suggests the involvement of CNV in pathophysiology of diseases. Conclusions This study shows the close correlation between CNV and differential gene expression revealing the qualitative relationship between genetic variation and its downstream effect, especially for oncogenes and tumor suppressor genes. It is of a critical importance to elucidate the relationship between copy number variation and gene expression for prevention, diagnosis and treatment of cancer.

scholarly journals Codon choice directs constitutive mRNA levels in trypanosomes

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Janaina de Freitas Nascimento ◽  
Steven Kelly ◽  
Jack Sunter ◽  
Mark Carrington
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Open Reading Frame ◽  
Mrna Turnover ◽  
Mrna Levels ◽  
Protein Coding ◽  
Reading Frame ◽  
Protein Coding Genes ◽  
The Relationship ◽  
Adaptation Index

Selective transcription of individual protein coding genes does not occur in trypanosomes and the cellular copy number of each mRNA must be determined post-transcriptionally. Here, we provide evidence that codon choice directs the levels of constitutively expressed mRNAs. First, a novel codon usage metric, the gene expression codon adaptation index (geCAI), was developed that maximised the relationship between codon choice and the measured abundance for a transcriptome. Second, geCAI predictions of mRNA levels were tested using differently coded GFP transgenes and were successful over a 25-fold range, similar to the variation in endogenous mRNAs. Third, translation was necessary for the accelerated mRNA turnover resulting from codon choice. Thus, in trypanosomes, the information determining the levels of most mRNAs resides in the open reading frame and translation is required to access this information.

scholarly journals New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

2010 ◽  
Vol 23 (6) ◽  
pp. 856-865 ◽  
Author(s):  
Concha Lopez-Gines ◽  
Rosario Gil-Benso ◽  
Ruben Ferrer-Luna ◽  
Rafael Benito ◽  
Eva Serna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Egfr Amplification ◽  
Relationship Of ◽  
The Relationship

scholarly journals Multiomic characterisation of high grade serous ovarian carcinoma enables high resolution patient stratification

2022 ◽  
Author(s):  
Robert L Hollis ◽  
Alison M Meynert ◽  
Caroline O Michie ◽  
Tzyvia Rye ◽  
Michael Churchman ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Ovarian Carcinoma ◽  
Copy Number ◽  
Immune Cell ◽  
Hazard Ratio ◽  
High Grade ◽  
Serous Ovarian Carcinoma ◽  
Molecular Landscape ◽  
The Relationship

Background: High grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer; most patients experience disease recurrence which accumulates chemoresistance, leading to treatment failure. Previous investigations have characterised HGSOC at the genomic and transcriptomic level, identifying subtypes of patients with differential outcome and treatment response. However, the relationship between molecular events identified at the gene sequence, gene copy number and gene expression levels remains poorly defined. Methods: We perform multi-layer molecular characterisation of a large retrospective HGSOC cohort (n=362) with detailed clinical annotation to interrogate the relationship between patient groups defined by gene mutation, copy number events, gene expression patterns and infiltrating immune cell burden. We construct a high resolution picture of the molecular landscape in HGSOC and identify features of tumours associated with distinct clinical behaviour in patients. Results: BRCA2-mutant (BRCA2m) and EMSY-overexpressing cases demonstrated prolonged survival (multivariable hazard ratio 0.40 and 0.53) and higher chemotherapy response rates at first- and second-line treatment. CCNE1-gained (CCNE1g) cases demonstrated shorter survival (multivariable hazard ratio 1.52, 95% CI 1.10-2.10), under-representation of FIGO stage IV cases (P=0.017) and no significant difference in treatment response. We demonstrate marked overlap between the TCGA- and derived subtypes: the TCGA DIF, IMR, PRO and MES subtypes correlated with the Tothill C4, C2, C5 and C1 subtypes (P<0.001). IMR/C2 cases displayed higher BRCA1/2m frequency (25.5% and 32.5%) and significantly greater infiltration of immune cells (P<0.001), while PRO/C5 cases had the highest CCNE1g rate (23.9% and 22.2%) and were uniformly low in immune cell infiltration. The survival benefit for cases with aberrations in homologous recombination repair (HRR) genes was apparent across all transcriptomic subtypes (hazard ratio range 0.48-0.68). There was significant co-occurrence of RB loss and HRR gene aberrations (P=0.005); RB loss was further associated with favourable survival within cases harbouring HRR aberrations (multivariable hazard ratio 0.50, 95% CI 0.30-0.84). Conclusions: These data paint a high resolution picture of the molecular landscape in HGSOC, better defining patients who may benefit most from specific molecular therapeutics and highlighting those for whom novel treatment strategies are needed to improve outcomes.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

scholarly journals Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1021
Author(s):  
Carla Abrahamian ◽  
Christian Grimm
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Convincing Evidence ◽  
Signaling Cascades ◽  
Cation Channels ◽  
Pore Channel ◽  
Different Types ◽  
Canonical Wnt ◽  
The Relationship

Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.

scholarly journals Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kylee H. Maclachlan ◽  
Even H. Rustad ◽  
Andriy Derkach ◽  
Binbin Zheng-Lin ◽  
Venkata Yellapantula ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Copy Number ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Flexible Tool ◽  
Whole Exome ◽  
Hematological Cancers ◽  
Relationship Of ◽  
The Relationship ◽  
Validation Series

AbstractChromothripsis is detectable in 20–30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.

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