Expression Levels of Three Genes in Patients Who Responded (Red) and Who Did Not Respond (Blue) to IFNβ

<p>(Source: [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020033#pmed-0020033-b21" target="_blank">21</a>])</p

Changes in the Expression of Genes Known to be Involved in the Canonical Wnt Pathway

<p>The figure was generated using Ingenuity Pathways Analysis (Ingenuity Systems, <a href="http://www.ingenuity.com/" target="_blank">http://www.ingenuity.com/</a>). Increased genes are in increasing shades of red, decreased are in increasing shades of green. Combined red and green is when different members are changed in different directions.</p

Schematic Overview of the Epithelial–Mesenchymal Transition as Modulated by TGF-β and BMPs

<p>In IPF lungs, TGF-β3, gremlin, and LEF-1 are up-regulated, while BMP-2 is down-regulated. Dysregulation of TGF-β/BMP pathway induces a fibrotic phenotype. EMT, so important in development, is likely to represent one possible response of the alveolar epithelial cell facing sustained injury. Increased expression of BMPs may not only antagonize TGF-β-induced EMT, enhancing re-epithelialization, but also may cause the opposite process, mesenchymal-to-epithelial transition (MET).</p

Warm Autopsy Process

<p>Warm Autopsy Process</p

iDREM: Interactive visualization of dynamic regulatory networks

<div><p>The Dynamic Regulatory Events Miner (DREM) software reconstructs dynamic regulatory networks by integrating static protein-DNA interaction data with time series gene expression data. In recent years, several additional types of high-throughput time series data have been profiled when studying biological processes including time series miRNA expression, proteomics, epigenomics and single cell RNA-Seq. Combining all available time series and static datasets in a unified model remains an important challenge and goal. To address this challenge we have developed a new version of DREM termed interactive DREM (iDREM). iDREM provides support for all data types mentioned above and combines them with existing interaction data to reconstruct networks that can lead to novel hypotheses on the function and timing of regulators. Users can interactively visualize and query the resulting model. We showcase the functionality of the new tool by applying it to microglia developmental data from multiple labs.</p></div

iDREM visualization functions.

<p><b>Top</b>: Expression of a regulator (E2F5) (<b>A</b>) and its targets (<b>B</b>). <b>2nd row</b>: Expression patterns (similar to the original DREM result, can be viewed from the tool as well) (<b>C</b>) and the regulators for each of these splits (<b>D</b>). <b>3rd row</b>: Methylation of a regulator (<b>E</b>) and its targets (<b>F</b>). <b>4th row</b>: Integration with additional browsers for viewing epigenetic data for specific TFs / genes (<b>G</b>) and protein level for specific TFs/proteins (<b>H</b>). <b>5th row</b>: Intersection of path genes with single cell data (<b>I</b>) and integrated GO functional analysis (<b>J</b>).</p

Pol II ChIP-chip results for miR-10a.

<p>The blue arrow represents the location and transcriptional direction of hsa-miR-10a. The red dashes represent the location and value of the ChIP-chip probes. <i>TSS</i> – transcription start site of this miRNA.</p

The top 20 most significant <i>n</i>-mers for each of the two models and the Fisher score as well as the −log10 of their <i>p</i>-value from <i>Gist</i> package (<i>t</i>-test metric).

<p>Bold letters indicate the <i>n</i>-mer that appears to be a significant feature in both the CpG+ and CpG− models.</p

Identification of promoters of intergenic miRNA genes.

<p><i>miRNA</i>: miRNA gene symbol, multiple symbols designate cluster of co-expressed miRNAs; <i>Chromosomal location</i>: the chromosomal position and orientation of the miRNA gene; <i>ChIP-chip region</i>: the nearest region with a statistically significant peak; <i>CPPP model</i>: the CpG (CpG+) or non-CpG (CpG−) model used for the TSS prediction; <i>Predicted TSS</i>: TSS predicted by CPPP; <i>Distance</i>: the distance of the predicted TSS from the most 5′ pre-miRNA transcript. Bold letters designate previously verified TSSs.</p

Identification of promoters for <i>intragenic</i> miRNA genes.

<p>Column names as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005279#pone-0005279-t001" target="_blank">Table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005279#pone-0005279-t002" target="_blank">2</a>. Bold letters designate genes whose expression was found to be anti-correlated with their host genes.</p