Description of patient classes for AD iCAP.

<p>Description of patient classes for AD iCAP.</p

ALS classifier accuracies with 6 Huntington's disease samples included in test set.

<p>ALS classifier accuracies with 6 Huntington's disease samples included in test set.</p

The 134 genes from the ALS gene expression classifier.

<p>Genes that are either transcriptionally responsive to ER stress [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178608#pone.0178608.ref032" target="_blank">32</a>] or directly targeted by TFs ATF4 (Atf4) and CHOP (Ddit3) during ER stress [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178608#pone.0178608.ref032" target="_blank">32</a>] are shown as nodes (depicted using Cytoscape [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178608#pone.0178608.ref033" target="_blank">33</a>]). Node color indicates mean log₂ differential expression level in the indicator cell assay (disease versus normal) ranging from –0.44 (green) to 0.1 (pink). Node shape indicates genes that are transcriptionally responsive to ER stress (oval) or are not (hexagon) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178608#pone.0178608.ref032" target="_blank">32</a>]. 133 of the 134 genes are known to have human orthologs and underlined genes co-occur with “amyotrophic lateral sclerosis” in titles or abstracts of articles in PubMed (on 01/15/15).</p

Classifier pipelines.

<p>I. 47 training samples or 12 test samples passed through the pre-processing pipeline, which resulted in normalized gene intensity scores. II. The classifiers were trained. 12 non-carrier (non-car.) samples in the 47 training examples were used to construct a linear model of gene expression based on control genes, which was used to convert all gene intensities into log2 gene expression ratios. These ratios were used to identify differentially expressed gene sets and ultimately select 64 gene sets or 134 genes that could differentiate between non-carrier and pre-symptomatic carrier mice using SVMs. III. The classifiers were tested. Gene intensities from 12 pre-processed but de-identified examples were converted to expression ratios using the linear model trained in II, and data sets composed of the 64 gene sets or 134 genes identified in II were extracted. The de-identified examples described by these data sets were classified as carrier or non-carrier using the SVMs trained in II. The pipeline for Classifier 3 was identical to that of Classifier 1 except that a different GSA score threshold was used (|GSA| ≥ 1 instead of GSA ≤ -1), resulting in selection of 106 gene sets instead of 64. For classifier testing with Huntington’s samples, classifiers were trained with all 59 normal and disease samples (not shown) and tested against 6 Huntington’s samples. For each classifier configuration, the fraction of Huntington’s samples that were correctly predicted as non-carriers of the ALS mutation is shown as ‘Hunt’ tally.</p

Development of an indicator cell assay.

<p>For each disease indication, the global differential gene expression pattern of the indicator cells is measured in response to serum from normal and diseased subjects, and is used to identify a reliable disease classifier using a small number of features. To deploy the assay, the cell-based components can be automated and miniaturized, and the expression of classifier genes can be measured using a targeted, cost-effective and high-throughput readout to classify new subjects.</p

Blind accuracies of ALS classifiers.

<p>Blind accuracies of ALS classifiers.</p

A model for a causal role of cg27386326 methylation in <i>FADS</i> activities and resulting molecular and clinical phenotypes.

<p>A model for a causal role of cg27386326 methylation in <i>FADS</i> activities and resulting molecular and clinical phenotypes.</p

Association of <i>FADS</i> cluster CpG sites with rs174537.

<p>The lower panel shows the location of the CpG sites relative to the ENCODE data for H3K4Me1, H3K27Ac, and H3K4Me3 histone marks, respectively, which indicate promoter and/or regulatory regions in seven cell lines. The peak methylation site is shown in red, and the other two sites from the region that met Bonferroni adjustment are shown in blue.</p

Manhattan plots for association of rs174537 with HumanMethylation450 sites.

<p>P-values are based on the genetic trend test and adjusted for age, chip, and chip position. The blue line indicates the Bonferroni-adjusted level of significance of 1.03×10⁻⁷ (0.05/485,000). The upper panel shows results from the meta-analysis (using European Americans and African-Americans), the middle panel shows European Americans only, and the lower panel shows African-Americans only.</p

LcPUFA biosynthesis from dietary essential PUFAs Pathway.

<p>Key enzymes and metabolites are shown, and the roles of <i>FADS1</i> (red) and <i>FADS2</i> (blue) are indicated.</p