Detection of aberrant splicing products in HMeso01A harboring the <i>BAP1 c</i>.<i>2054 A>T</i> (p.E685V) mutation.

<p>PCR fragments generated from amplification of <i>BAP1</i> exons 14–17 on cDNAs from HMeso01A and 4 controls were separated by agarose gel electrophoresis. Marker: DNA marker PhiX 174-HaeIII digest ladder.</p

Comparative sequence analysis reveals the <i>BAP1 c</i>.<i>2054A</i> (p.E685) is highly conserved.

<p>A. Multi-species comparative genomic analysis of <i>BAP1 c</i>.<i>2054A</i> in ten distantly related species: human, chimpanzee, mouse, rat, dog, cat, rabbit, chicken, xenopus and zebrafish. B. Multiple sequence alignment indicates BAP1 p.E685 is well conserved across the same ten distantly related species.</p

Summary of splicing variants cloned from RT-PCR products of HMeso01A harboring the c.2054 A>T (p.Glu685Val) mutation.

<p>A. Retention of introns 14, 15, 16; B. Retention of intron 15, 16; C. Retention of intron 14 and 4 bp deletion (GAAG) at the end of exon 16; D. Retention of intron 16; E. Partial retention of 3’ 69 bp in intron 14 and 4 bp deletion (GAAG) at the end of exon 16; F. Partial retention of 3’ 18 bp in intron 15 and 4 bp deletion (GAAG) at the end of exon 16; G. 4 bp deletion (GAAG) at then end of exon 16 (Δ4). //: partial exon.</p

Kaplan-Meier plot.

<p>The three integrated subtypes of glioblastoma identified by iCluster show survival differences.</p

Comparing separate clustering and iCluster performance using simulation.

<p>Simulation scenario 1 consists of a pair of matched data sets of 200 features (20 of which are relevant to clustering and 180 are noisy features) in 100 samples belonging to two distinct clusters. Scenario 2 represents an extremely sparse data structure with only 2 cluster-associated features and 198 noisy features. RI is the resampling-based cluster reproducibility criterion and ranges between 0 and 1. A value close to 1 indicates perfect cluster reproducibility, and a value close to 0 indicates poor reproducibility. Separate K-means has two sets of numbers associated with each criterion because of separate model fits. The numbers are similar and therefore averaged in the table. The number in parentheses is the standard deviation over 50 simulations.</p

Integrated subtype reproducibility and number of subtype-discriminant features.

<p>Integrated subtype reproducibility and number of subtype-discriminant features.</p

Comparison of the iCluster method to PCA approaches in the GBM data set.

<p>Two-dimensional plots of the sample points in the latent subspace spanned by A) the first two joint latent factors obtained using iCluster, B) the first two principal components (PCs) from the concatenated data matrix, C) the first two sparse PCs from the concatenated data matrix, D) the first two PCs from the mRNA expression data alone, E) from the copy number data alone, and F) from the methylation data alone.</p

Comparing iCluster to a naive integration via PCA using simulated data.

<p>Two-dimensional plots of the sample points in the latent subspace by different methods. A set of 150 subjects are simulated belonging to three clusters (indicated by black, blue, and orange dots). Each subject has a pair of synthetic molecular profiles representing two data types each consisting of 1,000 features. A common set of 5 correlated features in both data type 1 and 2 defines the black subtype. Another set of 5 features specific to data type 2 defines the blue subtype. The remaining features are noise.</p

The iCluster framework.

<p>The iCluster framework.</p

Cluster separability plots in the GBM data set.

<p>Proportion of deviation (POD) is calculated as the proportion of deviation from a block diagonal structure. K = 3 has the best block-diagonal structure.</p