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Platform-Independent Genome-Wide Pattern of DNA Copy-Number Alterations Predicting Astrocytoma Survival and Response to Treatment Revealed by the GSVD Formulated as a Comparative Spectral Decomposition

Fig 2

Significant probelets and corresponding tumor and normal arraylets revealed by the GSVD of the LGA discovery datasets.

(a) Plot of the second most LGA tumor-exclusive tumor arraylet describes a genome-wide pattern of co-occurring CNAs across 933,827 Affymetrix probes. The probes are ordered, and their copy numbers are colored, according to each probe’s chromosomal location. This LGA pattern is encompassed in a GBM pattern, which was previously uncovered by the GSVD [8]. Segments (black lines) that were identified in the GBM pattern, and are amplified or deleted in the LGA pattern, are also amplified or deleted in the GBM pattern, respectively, and at a greater magnitude (Fig 3). The GBM-associated LGA-shared focal CNAs (black) include, e.g., a gain of a segment on chromosome 1 containing MDM4. (b) Plot of the second LGA probelet describes the variation of the weight, or superposition coefficient of the LGA pattern in the tumor profiles of the 59 patients. The second probelet classifies the patients into two groups of low (red) and high (blue) weights, which are of statistically significantly different prognoses (Fig 4). (c) Raster display of the tumor dataset shows the correspondence between the tumor profiles and the second LGA probelet and tumor arraylet. (d) Plot of the 53rd LGA normal arraylet, which is the most significant in the normal dataset, describes a deletion of the X chromosome. (e) Plot of the 53rd LGA probelet, which is approximately common to the tumor and normal datasets, describes a classification of the patients by gender into females (red) and males (blue). The corresponding hypergeometric P-value is <10−13. (f) Raster display of the normal dataset shows the male-specific X chromosome deletion across the normal genomes. This biological variation is conserved in the patient-matched LGA tumor genomes. The GSVD separates this variation from the second LGA tumor arraylet.

Fig 2