The impact of gene expression levels on probe selection.

<div><p>We grouped 17056 transcript clusters into ten distinct bins according to the height where we cut the clustering dendrogram (<i>h_final</i>).</p> <p>For each transcript cluster, we calculated its peak gene expression index in the 11 tissues using selected probes.</p> <p>Then we took an average for each bin.</p> <p>The values of tree cutoff (X-axis) were negatively correlated with average peak gene expression levels in the 11 tissues (Y-axis).</p></div

Hierarchical clustering of probe intensities of CD44 core probes.

<div><p>Core probes of CD44 are clustered by average linkage hierarchical clustering based on their intensities in 11 tissues (a total of 33 samples).</p> <p>The distance metric is (1-Pearson correlation coefficient).</p> <p>A total of 44 core probes are selected when we cut the clustering dendrogram at <i>h</i> = 0.1 (indicated by the dashed horizontal line).</p></div

Gene expression indexes computed using all probes, all core probes, and selected core probes.

<div><p>(<b>A</b>) Gene expression indexes of transcript cluster 2899110 (HFE) are computed using all probes (black circles), all core probes (red triangles) and selected probes (green rectangles).</p> <p>Probe selection increases the gene expression indexes computed for all the samples.</p> <p>The relative expression levels in different tissues remain unaltered.</p> <p>(<b>B</b>) Gene expression indexes of transcript cluster 3833500 (SPTBN4, a gene known to be overexpressed in brain and cerebellum).</p> <p>Probe selection strengthens the pattern of overexpression in cerebellum (sample #4, #5 and #6).</p></div

Probe design of exon arrays.

<div><p>(<b>A</b>) Exon-intron structure of a gene.</p> <p>Black boxes represent exons. Gray boxes represent introns. Introns are not drawn to scale.</p> <p>(<b>B</b>) Probe design of exon arrays.</p> <p>Exon arrays have four probes targeting each exon of the gene.</p> <p>(<b>C</b>) Probe design of 3′ expression arrays.</p> <p>Probes on 3′ expression arrays target 3′ end of the mRNA sequence.</p></div

Heatmap visualization of exon array pairwise probe correlations.

<div><p>(<b>A</b>) Heatmap visualization of probe intensities of HLA-DMB (transcript cluster 2950263).</p> <p>Each cell of the heatmap shows the correlation of two probes in 11 tissues.</p> <p>The top color bar indicates the probe type.</p> <p>Core probes are colored in red.</p> <p>Extended probes are colored in blue.</p> <p>The signal intensities of core probes usually have a high correlation (the top right corner of the heatmap).</p> <p>(<b>B</b>) Heatmap visualization of probe intensities of core probes in CD44 (transcript cluster 3326635).</p> <p>Probes targeting the 5′ and 3′ regions (constitutive exons) of CD44 show highly correlated signals in 11 tissues (the top right corner of the heatmap).</p> <p>(<b>C</b>) Heatmap visualization of probe intensities of core probes in CD44 (transcript cluster 3326635).</p> <p>Probes are ordered from top to bottom based on their genomic coordinates (5′ to 3′).</p></div

Effects of probe selection on genes differentially expressed between liver and muscle.

<div><p>(<b>A</b>) 438 transcript clusters were defined as overexpressed in liver relative to muscle, based on 3′ expression array data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000088#s2" target="_blank">Materials and Methods</a>).</p> <p>Using gene expression indexes computed from all core probes or the selected core probes, we calculated the average gene expression fold change in three liver samples over three muscle samples.</p> <p>The X-axis shows the fold change using all core probes, and the Y-axis shows the fold change using selected core probes.</p> <p>The red line indicates the 45-degree line (Y = X).</p> <p>(<b>B</b>) A magnification of (A) when the fold change computed from all core probes was less than 6.</p> <p>(<b>C</b>) 500 transcript clusters were defined as overexpressed in muscle relative to liver, based on 3′ expression array data (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000088#s2" target="_blank">Materials and Methods</a>).</p> <p>Using gene expression indexes computed from all core probes or the selected core probes, we calculated the average gene expression fold change in three muscle samples over three liver samples.</p> <p>The X-axis shows the fold change using all core probes, and the Y-axis shows the fold change using selected core probes.</p> <p>The red line indicates the 45-degree line (Y = X).</p> <p>(<b>D</b>) A magnification of (C) when the fold change computed from all core probes was less than 6.</p></div

Characteristics of the 24 SNPs in SAPHIR, KORA F3 and CoLaus, including genotype quality (call rate or imputation quality RSQR).

*<p>Minor and Major alleles based on the plus-strand.</p>**<p>Number of homozygotes for the major allele/heterozygotes/homozygotes for the rare allele; For KORA F3 and CoLaus, where imputed genotype scores have been used, this are the numbers of the “best guess” genotypes (KORA F3) and rounded sum of genotype scores.</p>***<p>Based on exact test of Hardy-Weinberg Equilibrium (HWE).</p

Linear model results on the 24 selected SNPs in the SAPHIR, KORA F3 and CoLaus study using an additive genetic model, adjusted for age, sex and BMI, as well as the combined fixed effects meta-analysis results.

<p>Effect estimates and standard errors (for the combined as well as sex-specific analyses) are based on the original adiponectin scale, whereas p-values are taken from the linear regression on log(adiponectin).</p

Schematic structure of <i>SREBF1</i> gene.

<p>Exons are numbered indicating the alternatively spliced -a and -c variants. Genomic location of the analyzed single nucleotide polymorphisms are marked. The single nucleotide polymorphisms highlighted in yellow showed a strongly associated with adiponectin levels in our study. The single nucleotide polymorphism highlighted in grey showed a significant association in a previous study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052497#pone.0052497-Felder1" target="_blank">[26]</a> and was only borderline significantly associated in the present study (p = 0.004).</p

Linkage disequilibrium structure across the <i>SREBF1</i> single nucleotide polymorphisms.

<p>The pair wise linkage disequilibrium (R² and D’) is given for each pair of single nucleotide polymorphisms. Color-coding is based on R². The diagonal line indicates the physical position of the single nucleotide polymorphisms relative to each other.</p