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. 2017 Dec 19;8:2187. doi: 10.1038/s41467-017-02181-0

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Increased correlations between genes from neighboring loci as a result of copy number variation. a Schematic diagram illustrating an example of copy number alteration confounding co-expression analysis. In this example, three subunits of a protein complex are encoded by three genes from different chromosomes. In normal tissues, coordinated transcriptional regulation ensures equal amounts of three subunits are produced to facilitate stoichiometric assembly of the complex. Transcript levels of these three genes will therefore be highly correlated. In tumor samples, the third gene is amplified together with a neighboring oncogene with unrelated functions. Consequently, correlation of the third gene with the other two related genes decreases, whereas its correlation with the unrelated oncogene neighbor increases. b Schematic diagram delineating correlation relationships between copy numbers of neighboring genes, between RNA levels of neighboring genes and between copy number and RNA levels of the same gene as a result of CNA events in cancer. c Relative copy number for genes on Chromosome 1 in 1075 tumor samples from TCGA breast cancer cohort. Genes are ordered by location on chromosome, and borders of cytobands from p and q arms are marked on top. P arm is frequently deleted and q arm is frequently amplified. d Copy number-RNA Pearson correlation matrix for genes from chromosome 1. Arm-level copy-number alteration events from chromosome 1 results in positive correlation between copy number and RNA for genes from the same arm. e RNA–RNA Pearson correlation matrix for genes from chromosome 1. Co-amplification or co-deletion of genes located in the same segment result in increased positive correlation between neighboring genes. f Copy number-RNA Pearson correlation matrix for all genes. Genes are ordered by location in chromosomes, and names of chromosomes are given on top. Increased positive correlation is observed only for genes from the same chromosome or chromosomal arm but not for genes from different chromosomes