ArticleBioinformatics (Oxford, England)2008
Integrative analysis reveals the direct and indirect interactions between DNA copy number aberrations and gene expression changes.
Article in Bioinformatics (Oxford, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- A meta-analysis of multiple matched copy number and transcriptomics data sets for inferring gene regulatory relationships.PloS one · 2014Pooled it
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- Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer.Cancers · 2018Article
- Cancer Subtype Discovery Using Prognosis-Enhanced Neural Network Classifier in Multigenomic Data.Technology in cancer research & treatment · 2018Article
- Multidimensional Integrative Genomics Approaches to Dissecting Cardiovascular Disease.Frontiers in cardiovascular medicine · 2017Review
- Translational compensation of genomic instability in neuroblastoma.Scientific reports · 2015Article
- Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential.BMC systems biology · 2015Review
- Contrasting cellular stress responses of Baikalian and Palearctic amphipods upon exposure to humic substances: environmental implications.Environmental science and pollution research international · 2014Article
- A test for comparing two groups of samples when analyzing multiple omics profiles.BMC bioinformatics · 2014Article
- Copy number variants and selective sweeps in natural populations of the house mouse (Mus musculus domesticus).Frontiers in genetics · 2014Review
- Gene expression is highly correlated on the chromosome level in urinary bladder cancer.Cell cycle (Georgetown, Tex.) · 2013Article
- Voting-based cancer module identification by combining topological and data-driven properties.PloS one · 2013Article
- Cancer gene prioritization by integrative analysis of mRNA expression and DNA copy number data: a comparative review.Briefings in bioinformatics · 2013Review
- Testing the utility of an integrated analysis of copy number and transcriptomics datasets for inferring gene regulatory relationships.PloS one · 2013Article
- Integrative genomics with mediation analysis in a survival context.Computational and mathematical methods in medicine · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
motivationDNA copy number aberrations (CNAs) and gene expression (GE) changes provide valuable information for studying chromosomal instability and its consequences in cancer. While it is clear that the structural aberrations and the transcript levels are intertwined, their relationship is more complex and subtle than initially suspected. Most studies so far have focused on how a CNA affects the expression levels of those genes contained within that CNA.
resultsTo better understand the impact of CNAs on expression, we investigated the correlation of each CNA to all other genes in the genome. The correlations are computed over multiple patients that have both expression and copy number measurements in brain, bladder and breast cancer data sets. We find that a CNA has a direct impact on the gene amplified or deleted, but it also has a broad, indirect impact elsewhere. To identify a set of CNAs that is coordinately associated with the expression changes of a set of genes, we used a biclustering algorithm on the correlation matrix. For each of the three cancer types examined, the aberrations in several loci are associated with cancer-type specific biological pathways that have been described in the literature: CNAs of chromosome (chr) 7p13 were significantly correlated with epidermal growth factor receptor signaling pathway in glioblastoma multiforme, chr 13q with NF-kappaB cascades in bladder cancer, and chr 11p with Reck pathway in breast cancer. In all three data sets, gene sets related to cell cycle/division such as M phase, DNA replication and cell division were also associated with CNAs. Our results suggest that CNAs are both directly and indirectly correlated with changes in expression and that it is beneficial to examine the indirect effects of CNAs. AVAILABILITY: The code is available upon request.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.