The 187 possible edges present in at least one of 500 networks are plotted

The 107 out of 187 edges are presented less than 25 times in 500 networks. The x-axis is the number of occurrences of the edges and the y-axis is the frequency.<p><b>Copyright information:</b></p><p>Taken from "Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants"</p><p>http://www.biomedcentral.com/1471-2164/9/288</p><p>BMC Genomics 2008;9():288-288.</p><p>Published online 16 Jun 2008</p><p>PMCID:PMC2478688.</p><p></p

There are 4 groups of significantly differentially expressed gene lists, one for comparison of necrosis level 0 vs

1 with 2683 significant genes, one for comparison of necrosis level 1 vs. 2 with 171 significant genes, one for comparison of necrosis level 2 vs. 3 with 910 significant genes, and one for comparison of necrosis level 3 vs. 4 with 131 significant genes. The four gene lists are labeled on the bottom of the figure and over-represented biological processes are labeled at the left of the figure. The red color indicates that the p-value is smaller than the FDR rate of 0.05 whereas blue represents p-values larger than an FDR rate of 0.05. The smaller the p-value, the more intense the color.<p><b>Copyright information:</b></p><p>Taken from "Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants"</p><p>http://www.biomedcentral.com/1471-2164/9/288</p><p>BMC Genomics 2008;9():288-288.</p><p>Published online 16 Jun 2008</p><p>PMCID:PMC2478688.</p><p></p

The reconstructed Bayesian network was generated from the gene expression data from a total of 32 gene profiles

It depicts the statistical dependence between the transcript levels of the genes. The red nodes represent the up-regulated genes and green nodes represent the down-regulated genes both when the necrosis severity increases. Blue edges have a probability greater than 0.9, brown edges between 0.8 to 0.9, and black edges between 0.6 to 0.8. The dashed lines represent the edges consistent with the Ingenuity Pathway Analysis in Figure 4.<p><b>Copyright information:</b></p><p>Taken from "Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants"</p><p>http://www.biomedcentral.com/1471-2164/9/288</p><p>BMC Genomics 2008;9():288-288.</p><p>Published online 16 Jun 2008</p><p>PMCID:PMC2478688.</p><p></p

PD-L1 staining patterns on NSCLC specimens using the 22C3 antibody concentrate on the Dako ASL48 platform (LDT) compared with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).

<p>(<i>A</i>) The PD-L1 22C3 pharmDx kit on the Dako ASL48 platform; (<i>B</i>) optimised LDT (primary antibody dilution 1:50, 30-minute incubation); (<i>C</i>) LDT using primary antibody dilution 1:100, 30-minute incubation; (<i>D</i>) primary antibody dilution 1:200, 30-minute incubation; (<i>E</i>) primary antibody dilution 1:100, 60-minute incubation; (<i>F</i>) primary antibody dilution 1:100, 120-minute incubation. Original magnification 5×. Inserts, original magnification 40×. PD-L1, programmed death ligand 1; NSCLC, non–small cell lung cancer; ASL48, Autostainer Link 48; LDT, laboratory-developed test; IHC, immunohistochemistry.</p

Use of the 22C3 anti–PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms

<div><p>Background</p><p>For non–small cell lung cancer (NSCLC), treatment with pembrolizumab is limited to patients with tumours expressing PD-L1 assessed by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx (Dako, Inc.) companion diagnostic test, on the Dako Autostainer Link 48 (ASL48) platform. Optimised protocols are urgently needed for use of the 22C3 antibody concentrate to test PD-L1 expression on more widely available IHC autostainers.</p><p>Methods</p><p>We evaluated PD-L1 expression using the 22C3 antibody concentrate in the three main commercially available autostainers Dako ASL48, BenchMark ULTRA (Ventana Medical Systems, Inc.), and Bond-III (Leica Biosystems) and compared the staining results with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Several technical conditions for laboratory-developed tests (LDTs) were evaluated in tonsil specimens and a training set of three NSCLC samples. Optimised protocols were then validated in 120 NSCLC specimens.</p><p>Results</p><p>Optimised protocols were obtained on both the VENTANA BenchMark ULTRA and Dako ASL48 platforms. Significant expression of PD-L1 was obtained on tissue controls with the Leica Bond-III autostainer when high concentrations of the 22C3 antibody were used. It therefore was not tested on the 120 NSCLC specimens. An almost 100% concordance rate for dichotomized tumour proportion score (TPS) results was observed between TPS ratings using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Interpathologist agreement was high on both LDTs and the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform.</p><p>Conclusion</p><p>Availability of standardized protocols for determining PD-L1 expression using the 22C3 antibody concentrate on the widely available Dako ASL48 and VENTANA BenchMark ULTRA IHC platforms will expand the number of laboratories able to determine eligibility of patients with NSCLC for treatment with pembrolizumab in a reliable and concordant manner.</p></div

Intraclass correlation coefficient of TPS rating for each of the PD-L1 IHC assays using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms (LDTs) relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).

<p>Intraclass correlation coefficient of TPS rating for each of the PD-L1 IHC assays using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms (LDTs) relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).</p

PD-L1 staining patterns on NSCLC specimens using the 22C3 antibody concentrate on the VENTANA BenchMark ULTRA platform (LDT) compared with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).

<p>(<i>A</i>) The PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform; (<i>B</i>) optimised LDT (CC1 64 minutes, 22C3 primary antibody dilution 1:50, OptiView amplification 12 minutes); (<i>C</i>) CC1 32 minutes, primary antibody dilution 1:50, OptiView amplification 12 minutes; (<i>D</i>) CC1 64 minutes, primary antibody dilution 1:50, OptiView amplification 4 minutes; (<i>E</i>) CC1 32 minutes, primary antibody dilution 1:100, OptiView amplification 12 minutes; (<i>F</i>) CC1 64 minutes, primary antibody dilution 1:100, OptiView amplification 12 minutes. Original magnification 5×. Inserts, original magnification 40×. PD-L1, programmed death ligand 1; NSCLC, non–small cell lung cancer; ASL48, Autostainer Link 48; LDT, laboratory-developed test; IHC, immunohistochemistry.</p

PPA and NPA for each of the PD-L1 IHC assays using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms (LDTs) relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).

<p>PPA and NPA for each of the PD-L1 IHC assays using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms (LDTs) relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform (gold standard).</p