Additional file 2 of An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks

Includes comparative results of standard WGCNA and k-means on simulated data. (CSV 4 kb

Additional file 4 of An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks

Heat-maps showing −l o g 10(p-values) from Ficher’s Exact test on significant concentration of specific cell marker gene sets (rows) on each tissue module (columns). The one within the Additional file 1 corresponds to the standard WGCNA. (JPG 1198 kb

Additional file 2: of Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis

This file includes additional tables to complement and support the main text. (PDF 18446 kb

List of identified <i>LRRK2</i> eQTLs in three gene expression datasets: brain (n = 134), liver (n = 970) and monocytes (n = 1,490).

<p>For the P-value computations in brain samples, <i>LRRK2</i> expression values are averaged across all 10 brain regions. MAF: minor allele frequency. ^a: See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070724#pone.0070724.s002" target="_blank">Figure S2</a>. ^b: See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070724#pone.0070724.s001" target="_blank">Figure S1</a>.</p

Common variant associations in the <i>LRRK2</i> region for PD, CD and leprosy.

<p>The CD GWAS results indicate a minimum of two independent associations. For each disease association we list the P-values in the expression datasets. NS: not-significant (<i>P</i>>0.001). (a): See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070724#pone.0070724.s003" target="_blank">Figure S3</a>.</p

Regional variability in LRRK2 expression.

<p>(<b>A</b>) Box plot of mRNA expression levels for <i>LRRK2</i> in 10 brain regions, based on microarray experiments and plotted on a log2 scale (y axis). Whiskers extend from the box to 1.5 times the inter-quartile range. (<b>B</b>) Box plot of mRNA expression levels for <i>LRRK2</i> in 4 brain regions, based on QuantiGene experiments. Whiskers extend to the maximum and minimum values. Stars indicate significant differences in expression between brain regions (p-value <0.01, Wilcoxon signed rank testing). (<b>C</b>) Dot plot of mRNA expression levels for <i>LRRK2</i> in 3 brain regions based on TaqMan Real Time PCR experiments. The expression levels were normalized to the geometric mean of 3 housekeeping genes. The graph shows higher expression in OCTX compared with other regions. Abbreviations: frontal cortex (FCTX), occipital cortex (specifically primary visual cortex, OCTX), temporal cortex (TCTX), intralobular white matter (WHMT), thalamus (THAL), putamen (PUTM), substantia nigra (SNIG), hippocampus (HIPP), medulla (specifically inferior olivary nucleus, MEDU) and cerebellum (CRBL).</p

RT-PCR results showing evidence of amplifiable splice forms across exons 32–33 of LRRK2 in selected brain regions, occipital cortex (OCTX), substantia nigra (SNIG), medulla (MEDU) and cerebellum (CRBL).

<p>(<b>A</b>) RT-PCR results confirming the splicing out of exons 32–33 in SNIG, compared with the other brain regions tested. The expected band size for the isoform with exon 32–33 included is 470 bps, whereas that for the isoform with exon 32 alone spliced out is 270 bps. These results show splicing out of exons 32–33 in substantia nigra and the existence of an isoform with exon 32 alone spliced out in OCTX, MEDU and CRBL. (<b>B</b>) RT-PCR results further confirm the splicing out of exon 33 in SNIG. While OCTX, MEDU and CRBL show the expected band size of 195 bps suggesting that exon 32–33 is not spliced out in these regions, SNIG does not.</p

Additional file 1: of Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing

Includes all 12 additional tables with every table on a separate spreadsheet. The file format is an Excel spreadsheet. (XLSX 183 kb

Enrichment for coding variants amongst autosomal SNPs stratified between South Asians and the 1000 Genome populations (3A) and for specific functional classes of SNPs amongst South Asians compared to Europeans (3B).

<p>Enrichment is calculated compared to null hypothesis; P values are provided in <b>Table S6 and Table S7 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102645#pone.0102645.s021" target="_blank">File S1</a></b>.</p

Enrichment for stratified genetic variants at genetic loci associated with respective phenotype in genome-wide association studies.

<p>Inset the correlation between the enrichment for stratified SNPs at known genetic loci, and enrichment of stratified variants for SNPs associated with respective phenotype in genome-wide association studies. Further details are provided in <b>Table S10 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102645#pone.0102645.s021" target="_blank">File S1</a></b>.</p