Additional file 3 of Towards a more molecular taxonomy of disease

Change in performance of Parent Promotion depending on the size of disease-gene association information: Edge Correctness, Ancestor Correctness, Ancestor Precision/Recall and F-score for 23 MeSH trees. (PDF 53 kb

Additional file 1 of Towards a more molecular taxonomy of disease

Performance of three disease hierarchy inference algorithms (Parent Promotion, CliXO, MWST): Edge Correctness, Ancestor Correctness, Ancestor Precision/Recall and F-score for 23 MeSH trees. (PDF 78 kb

Stacked Gold Nanodisks for Bimodal Photoacoustic and Optical Coherence Imaging

Herein, we report on biological imaging nanoprobes: physically synthesized gold nanodisks that have inherent optical advantagesa wide range of resonant wavelengths, tunable ratio of light absorption-to-scattering, and responsiveness to random incident lightdue to their two-dimensional circular nanostructure. Based on our proposed physical synthesis where gold is vacuum deposited onto a prepatterned polymer template and released from the substrate in the form of a nanodisk, monodisperse two-dimensional gold nanodisks were prepared with independent control of their diameter and thickness. The optical benefits of the Au nanodisk were successfully demonstrated by the measurement of light absorbance of the nanodisks and the application of stacked nanodisks, where a smaller sized Au nanodisk was laid atop a larger nanodisk, as bimodal contrast agents for photoacoustic microscopy and optical coherence tomography

The VEGF pathway and its relevance to both BPD hypotheses.

<p>The relationships shown here are derived from the VEGF, PI3K-AKT, mTOR, and HIF-1 signaling pathways and the “Pathways in Cancer” map in the KEGG Pathway database. Dashed lines represent indirect regulation. Genes highlighted in orange are the five lung development genes implicated in ROP.</p

Example of comparison between pooling approach and traditional approach.

<p>Illustration of the process for calculating and for the th random trial. 100 gene-disease associations involving genes in the query gene set are withheld. Using the remaining associations, p-values for enrichment of the disease gene set at each node are computed using both the traditional and pooling approaches. Nodes are assigned to or based on which approach shows more significant enrichment, and the rate at which each set is supported by withheld links is computed. The idea is that if a disease class is correctly linked to the query gene set, it should be more likely to be supported by withheld gene-disease associations from that same query set.</p

Histogram showing - for each query gene set.

<p>The red lines show a difference of zero; values to the left of these lines represent individual random trials in which the traditional method outperformed the pooling method. This occurred only once, in one trial for the skin development gene set.</p

Expected results by tissue.

<p>Density of enrichment of developmental gene sets (labels on the right) in major disease subtrees. Values are z-score normalized densities, computed as described in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003578#s3" target="_blank">Methods</a>. Darker squares indicate that a larger fraction of the disease terms in the MeSH category have significant enrichment () of genes in the indicated gene set. Expected connections appear approximately along the diagonal in the first 7 columns, and throughout the rightmost two columns.</p

Advantage of the pooling approach.

<p>Average probabilities (over 100 trials) that random, withheld gene-disease links support nodes more significant by the traditional method () or the proposed pooling method () for the 9 query gene sets. Significance in each trial was computed without the withheld links. When is larger than , the nodes that are more significant under the pooling approach tend to be more consistently supported by the withheld data, our proxy for correctness.</p

Finding Novel Molecular Connections between Developmental Processes and Disease

<div><p>Identifying molecular connections between developmental processes and disease can lead to new hypotheses about health risks at all stages of life. Here we introduce a new approach to identifying significant connections between gene sets and disease genes, and apply it to several gene sets related to human development. To overcome the limits of incomplete and imperfect information linking genes to disease, we pool genes within disease subtrees in the MeSH taxonomy, and we demonstrate that such pooling improves the power and accuracy of our approach. Significance is assessed through permutation. We created a web-based visualization tool to facilitate multi-scale exploration of this large collection of significant connections (<a href="http://gda.cs.tufts.edu/development" target="_blank">http://gda.cs.tufts.edu/development</a>). High-level analysis of the results reveals expected connections between tissue-specific developmental processes and diseases linked to those tissues, and widespread connections to developmental disorders and cancers. Yet interesting new hypotheses may be derived from examining the unexpected connections. We highlight and discuss the implications of three such connections, linking dementia with bone development, polycystic ovary syndrome with cardiovascular development, and retinopathy of prematurity with lung development. Our results provide additional evidence that plays a key role in the early pathogenesis of polycystic ovary syndrome. Our evidence also suggests that the <i>VEGF</i> pathway and downstream <i>NFKB</i> signaling may explain the complex relationship between bronchopulmonary dysplasia and retinopathy of prematurity, and may form a bridge between two currently-competing hypotheses about the molecular origins of bronchopulmonary dysplasia. Further data exploration and similar queries about other gene sets may generate a variety of new information about the molecular relationships between additional diseases.</p></div

Detailed view of part of the Nervous System Disease subtree, showing enrichment of bone development genes.

<p>Links to dementia and Alzheimer's disease are shown. Significance of each node in the tree is represented by color; a gradient of shades of blue indicates p-values ranging from 0 (darkest blue) to 1.0 (white). Clicking on a node or selecting a set of nodes allows users to see, in the box in the upper right corner, the selected disease terms, p-values, and genes shared between those diseases and the developmental gene set.</p