Comparison of heuristic and exact algorithms.

<p>Distributions of enrichment <i>p</i>-values of the PMs identified by the Dendrix-top200, ME-uw, and ME algorithms.</p

p18 stimulates ES growth associated with upregulation of stemness genes.

<p>(A) The percentage of G1-phase cells in D3, B6 and <i>p18^−/−</i> cell lines with or without p18 overexpressing. (B) Growth curves plotted for WT, vector control, p18-overexpressing, and p18-GFP-overexpressing ES cells at different time points. (C) Real-time PCR assays of <i>Oct4</i>, <i>Nanog</i>, <i>Sox2</i>, <i>Rex1</i>, and <i>Sall4</i> were also performed for all three ES cell lines (e.g., D3, B6 and <i>p18^−/−</i>). Data were analyzed according to the ΔC_T method and values were normalized to β-actin. Values are expressed as the mean ± SD. In A-C, data represent three independent experiments with similar results.</p

Supplementary Figure 1 from YM-155 Potentiates the Effect of ABT-737 in Malignant Human Glioma Cells via Survivin and Mcl-1 Downregulation in an EGFR-Dependent Context

PDF file - 69K, Effect of YM-155 and ABT-737 on human astrocytes</p

Sequences of the Primers used for Real-time RT-PCR assays.

<p>Sequences of the Primers used for Real-time RT-PCR assays.</p

The PM corresponding to RM U_GO0051128.

<p><b>A</b>) Overlap between the PM U_GO0051128 and a known pathway. <b>B</b>) Overlap of the PM U_GO0051128 with the RB pathway. <b>C</b>) SGA pattern of the PM U_GO0051128. <b>D</b>) Genes in the PM U_GO0051128 closely interacting with other oncogenes. <b>E</b>) SGA pattern of the PM D_GO0006915.</p

Overlapping of genes in RM U_GO0051128 with an IPA network.

<p>A total of 10 out of 11 genes in the RM overlap with an IPA network (highlighted).</p

A diagram reflecting the signaling systems of a cancer cell.

<p>A signal pathway usually consists of a cascade of proteins, represented as rectangle (receptors) and circle (intracellular) nodes. Different pathways transmit signals regulating expression of distinct sets of target genes. In cancers, a pathway can be perturbed by an SGA event affecting a member protein (indicated by a red node); a cancer cell usually has multiple pathways perturbed.</p

Ectopic expression of p18 inhibits teratoma formation of mouse ES cells.

<p>(A) Growth curve of teratoma obtained. Tumor size was monitored daily, then documented once tumor growth became visible (e.g., days 7–28). The graph represents the tumor growth volume observed for the different groups (as labeled) at different time points until the tumors were excised. (B) Approximately one month after implantation, tumors were excised and weighed. Representative images of one set of tumors derived from p18 mouse ES and control vector mouse ES are shown. (C) H&E staining of teratoma sections. All three germ layers were detected (e.g., ectoderm, endoderm and mesoderm). In A-C, data represent three independent experiments with similar results.</p

Establishment of “loss-of-function” and “Gain-of-function” models.

<p>(A) Generation of <i>p18^−/−</i> ES cells by nuclear transfer. Briefly, the nuclei of <i>p18^−/−</i> BM cells were microinjected into enucleated oocytes, and nuclear transfer (NT) embryos developed into blastocysts. These blastocyts were selected for derivation of <i>p18^−/−</i> ES cells. (B) The genotype analysis of <i>p18^−/−</i> ES cell line. (C) RT-PCR assays to detect mRNA levels of p18 in wild type (WT) and <i>p18^−/−</i> ES cells. (D) Protein expression of p18 in WT and <i>p18^−/−</i> ES cells detected by western blotting. β-actin was used as a loading control. (E) Growth curves for WT and <i>p18^−/−</i> ES cells determined by counting the number of cells present at each time point using trypan blue staining. (F) Chimeric mice were generated by injecting <i>p18^−/−</i> ES cells into diploid blastocysts. Reconstituted embryos were then developed in the uteri of foster mothers and chimera pups were obtained 19 days after injection. (G) Schematic representation of the lentiviral vectors used in this study. The vector, iDuet101, contains an EF1 promoter that drives the expression of GFP, p18, or a p18-GFP fusion protein. CMV, cytomegalovirus; R, repeat region in the viral long terminal repeat; U5 regions in the viral long terminal repeat; EF, elongation factor 1α; GFP, green fluorescent protein gene; PGK, mouse phosphoglycerate kinase promoter; <i>Hyg+</i>, hygromycin resistance gene; LTR, long terminal repeat of lentiviral DNA. (H) RT-PCR detection of mRNA levels in mouse ES cells transduced with p18-GFP or p18. Briefly, transduced cells for both groups were selected with hygromycin-B (I), and then infected with the iDuet101-GFP, as well as iDuet101-p18, or p18-GFP, lentiviruses. Top panel (D3 ES), middle panel (B6 ES), and lower panels (<i>p18^−/−</i> ES) represent bright field images obtained, as well as fluorescence microscopy images added as inserts. WT: parental ES cells; +vector: iDuet 101-GFP; +p18: iDuet 101-p18; and +p18 - GFP: iDuet 101-p18 - GFP transduced ES cells. (J) Real-time RT-PCR detection of p18 mRNA in mouse ES cells transduced with or without p18 or p18-GFP. Data were analyzed according to the ΔC_T method. Values are expressed as the mean ± SD from two independent experiments, and all values were normalized to levels of β-actin. (K) Western blot analysis for p18 expression in three different ES cell lines with or without p18 or p18-GFP overexpression. *, p18-GFP. In B-E, H-K, data represent three independent experiments with similar results.</p

The impact of the signal-oriented approach on the qualities of PMs.

<p><b>A</b>) Distributions of D-weight. <b>B</b>) Distributions of enrichment <i>p</i>-values. (Note: D-weight – the solution weight defined by Dendrix, where a solution with high coverage (of tumors) and low overlap will have a high score. The Enrichment <i>p</i>-value – the solution weight defined by our method, where a solution whose somatic mutation and copy number alteration are enriched in tumors that perturb a common signal will have a good <i>p</i>-value.)</p