Additional file 2: of Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata

MS/MS analysis of Xac-2. (DOCX 157 kb

Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of β2-microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β2-microglobulin (β2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography–linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aβ2M amyloid fibril formation in vitro. We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as β2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aβ2M amyloid fibril formation. HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aβ2M amyloidogenesis by reducing the amyloid-related proteins.</p

The best predictive model for IgAN based on all the genotyped SNPs and their pairwise interaction terms.

<p>This model represents the solution of a stepwise logistic regression algorithm (BIC-based stepwise model selection). The coefficients from this model are used to refine the risk score for IgAN.</p

Conditional analysis of the <i>HLA-DQB1, HLA-DQA1, HLA-DRB1</i> locus.

<p>Conditional analysis of the <i>HLA-DQB1, HLA-DQA1, HLA-DRB1</i> locus.</p

Genetic risk and IgAN–attributable ESRD among major US ethnicities.

<p>The relationship between IgAN risk scores (red line) and IgAN incidence and prevalence (bars) among US ethnicities are shown. The following metrics of IgAN occurrence are depicted: (panel a) the incidence of ESRD due to IgAN per million population by ethnicity, (panel b) the prevalence of ESRD due to IgAN per million population by ethnicity, (panel c) percent of IgAN among the total ESRD population by ethnicity; and (panel d) percent of IgAN among ESRD due to glomerular disease by ethnicity.</p

Multiplicative interaction between Chr. 22q12 (rs2412971) and Chr. 1q32 (rs6677604) loci.

<p>The allelic effects of rs2412971-A by genotype class of rs9275596 (top signal in the HLA, no interaction) and rs6677604 (top signal in at <i>CFHR1/R3</i> locus on Chr. 1q32, significant interaction). The protective effect of rs2412971-A allele is reversed in homozygotes for the rs6677604-A allele, which tags a deletion in <i>CFHR3/R1</i>. The allelic effects are expressed on the log-odds scale and correspond to beta coefficients of the logistic regression model. Error bars correspond to 95% confidence intervals.</p

Replication Study Results and Combined Meta-Analysis.

<p>Combined association results for 12 SNPs representing 5 independent regions that reached genome-wide significance in the original GWAS. The combined effect estimates (per allele odds ratios) in the replication cohorts were all direction-consistent with the ones in the original GWAS cohorts. Significant heterogeneity was noted only for the second HLA locus represented by rs9357155 and rs2071543.</p><p>Q-test: P-value for the Cochrane's Q statistic for heterogeneity, NS: heterogeneity test not significant,</p>*<p>heterogeneity P<0.05,</p>**<p>heterogeneity P<0.01;</p><p>I²: Heterogeneity Index (0–100%), where <25% corresponds to low, 50%–75% to medium, and >75% to high level of heterogeneity;</p><p>OR: Additive (per-allele) Odds Ratio;</p>#<p>Han and Eskin random effects model.</p

Worldwide geospatial risk analysis.

<p>Surface interpolation of the standardized risk score over Africa and Euroasia (main), and Americas (inset). Symbols represent the locations of sampled populations: HGDP (circles), HapMap-III (diamonds), and healthy controls from this study (triangles).</p

Haplotype analysis of rs9275224, rs2856717, rs9275424, and rs9275596 at the HLA-DQB1/DRB1 locus.

<p>The most common haplotype of 4 major alleles (GCAT) is used as a reference to derive odds ratios for all other haplotypes. Only common haplotypes (frequency >1%) are tested for association.</p

Differences in the distribution of the 7-SNP genetic risk score by ethnicity.

<p>Only healthy control participants of the replication studies that were fully genotyped at all 7 loci were used in this analysis. Similar to the GWAS study, the risk score distributions were significantly different by ethnicity (ANOVA p = 2.1×10⁻³⁸). The corresponding differences in the distribution of risk alleles are depicted in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002765#pgen.1002765.s001" target="_blank">Figure S1</a>.</p