This kind of analysis pinpoints continuous clusters of co-expressed genes and permits to visualize their chromosomal organization. For all following tests, TCA was performed to verify the robustness of clusters.
An in silico study conducted by Buness et al. (14 (link)) identified 32 series of 20 characteristic overexpressed genes for amplified chromosomal regions. Six hundred and forty genes were tested for all patients and molecular subtypes. We considered as positive results continuous clusters of correlated co-expressed genes composed of at least three genes with r ≥ 0.30 and P ≤ 0.05. To quantify the global relationship among a cluster of co-expressed genes, eigenvalues of the correlation matrix were computed, and the ratio of the largest one to the sum of all eigenvalues multiply by 100 was taken (i.e. it comes to perform a principal component analysis based on the correlation matrix and take the percentage of variance explained by the first principal component) (Supplementary Method ). This value is called multicorrelation score (MCS).
ESR1 : A recent study showed that ESR1 was co-expressed with closely adjacent genes at 6q25.1 (15 (link)).
8p11-12 amplicon : At 8p11-12, one of the most frequently amplified regions in breast cancer (10–15% of cases), Bernard-Pierrot et al. identified five genes (LSM1, BAG4, DDHD2, PPAPDC1B and WHSC1L1) as consistently overexpressed due to an increased gene copy number (16 (link), 17 (link)).
Chromosome 17 : Chromosome 17 is highly amplified in breast cancer, especially in HER2+ molecular subtype. Its amplified regions permit to distinguish HER2+ and luminal A (5 (link), 18 (link)). We chose three genes in different regions of chromosome 17 to test bc-GenExMiner analyses: TRAF4 at 17q11-q12, MED24 at 17q21.1 and GGA3 at 17q25.1 (14 (link)).
ER status : Numerous studies showed that CNA varied among breast tumours with different ER status (4 (link), 5 (link), 19–21 (link)). A list of 59 genes, which demonstrated different expression profile according to ER status in gained regions, was tested to screen for DNA continuous clusters of correlated co-expressed genes (20 (link)). We chose the following criterion: at least two DNA continuous genes with correlated gene-expressions, to define clusters of correlated co-expressed genes. MCS was used to compare clusters of co-expressed genes.
An in silico study conducted by Buness et al. (14 (link)) identified 32 series of 20 characteristic overexpressed genes for amplified chromosomal regions. Six hundred and forty genes were tested for all patients and molecular subtypes. We considered as positive results continuous clusters of correlated co-expressed genes composed of at least three genes with r ≥ 0.30 and P ≤ 0.05. To quantify the global relationship among a cluster of co-expressed genes, eigenvalues of the correlation matrix were computed, and the ratio of the largest one to the sum of all eigenvalues multiply by 100 was taken (i.e. it comes to perform a principal component analysis based on the correlation matrix and take the percentage of variance explained by the first principal component) (
