Additional file 2: Figure S2. of tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine

Comparison of quality by depth (QD) from CAKUT and ExAC. Sites that were filtered out of ExAC (VQSR filtering) are shown in red. Sites that were marked as “PASS” in ExAC are shown in gold. Sites that were Not Sanger validated are shown in green. Sites that were Sanger Validated are shown in teal. Sites filtered by tarSVM are shown in blue. Sites that passed tarSVM are shown in purple. Quality by depth is correlated with mean allele balance, as is being used as a proxy for it. It is clear that there is a very clear separation between variants that are filtered by tarSVM and variants that pass tarSVM. Most of the variants filtered by tarSVM have a much lower quality than the pass variants. Variants that are Sanger validated are stronger correlated with variants that pass tarSVM. Variants that are labeled “PASS” in ExAC have a higher variant quality that the microfluidic data. The filtered variants in ExAC have a more flat distribution that those filtered by tarSVM. It is important to note, the variants that underwent Sanger sequencing were selected because they had the characteristics of true variants. This is why there is so much overlap between the distributions for Sanger validated variants and Not Sanger validated variants. (PPTX 121 kb

Additional file 2: Figure S2. of tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine

Comparison of quality by depth (QD) from CAKUT and ExAC. Sites that were filtered out of ExAC (VQSR filtering) are shown in red. Sites that were marked as “PASS” in ExAC are shown in gold. Sites that were Not Sanger validated are shown in green. Sites that were Sanger Validated are shown in teal. Sites filtered by tarSVM are shown in blue. Sites that passed tarSVM are shown in purple. Quality by depth is correlated with mean allele balance, as is being used as a proxy for it. It is clear that there is a very clear separation between variants that are filtered by tarSVM and variants that pass tarSVM. Most of the variants filtered by tarSVM have a much lower quality than the pass variants. Variants that are Sanger validated are stronger correlated with variants that pass tarSVM. Variants that are labeled “PASS” in ExAC have a higher variant quality that the microfluidic data. The filtered variants in ExAC have a more flat distribution that those filtered by tarSVM. It is important to note, the variants that underwent Sanger sequencing were selected because they had the characteristics of true variants. This is why there is so much overlap between the distributions for Sanger validated variants and Not Sanger validated variants. (PPTX 121 kb

Additional file 4: of tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine

Supplemental Notes #2. (DOCX 50 kb

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

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

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

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

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

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