Measure of the impact of the number of bootstrap samples on the size and the relevance of the candidate haplotypes space for the APOE gene

<p><b>Copyright information:</b></p><p>Taken from "ISHAPE: new rapid and accurate software for haplotyping"</p><p>http://www.biomedcentral.com/1471-2105/8/205</p><p>BMC Bioinformatics 2007;8():205-205.</p><p>Published online 15 Jun 2007</p><p>PMCID:PMC1919397.</p><p></p> Black line and left scale are for ICR (capture rate of true haplotypes configurations). Dashed line and right scale are for ANCR (average number of candidates per genotype)

MOESM2 of Predictiveness curves in virtual screening

Additional file 2: Table S2. Summary of the partial metrics at 2 % and 5 % of the ordered dataset for virtual screens performed using ICM

MOESM3 of Predictiveness curves in virtual screening

Additional file 3: Table S3. Summary of the partial metrics at 2 % and 5 % of the ordered dataset for virtual screens performed using Autodock Vina

MOESM1 of Predictiveness curves in virtual screening

Additional file 1: Table S1. Summary of the partial metrics at 2 % and 5 % of the ordered dataset for virtual screens performed using Surflex-dock

List of the significant associations (<i>p</i> ≤ 0.05) with slow and non-progression.

<p>(*) Note that rs3749971 is in linkage disequilibrium with rs3130350 and is therefore not considered an independent finding in our statistics (see text).</p><p>Alleles, allele frequencies (AF), positional data and genetic modes are provided with the results of the statistical inferences. Opposite signs for the β coefficients are required for an association to be replicated in the GRIV (non-progression) and ACS cohorts (time to AIDS93).</p

List of SNP/gene pairs associated with AIDS progression.

<p>(*) Note that rs3749971 is in linkage disequilibrium with rs3130350 and is therefore not considered an independent finding (see text).</p><p>The genetic association is linked back to its association with gene expression levels to provide an association between transcription levels (we use the word ‘regulation’ for convenience’s sake) and AIDS progression.</p

Statistical significance of our associations.

<p>Histogram of the number of SNPs that pass the significance criterion for this study using phenotype and SNP randomisations. These results provide us with a way to estimate the sensitivity of our study (diamond): it would be extremely unlikely for our eight independent findings to arise by chance alone (<i>p</i> = 0.001).</p

DataSheet_1_The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control.docx

IntroductionWe have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers.MethodsWe performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region.ResultsOur analysis identified 2,626 SNPs significantly associated (pDiscussionThese findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control.</p

Schematic summary of our methodology.

<p>The data from three databases are integrated to provide us with functional SNPs likely to be associated with changes in gene transcription in the tissue of interest. Using the SNAP Pairwise LD server, we only kept independent SNPs by removing superfluous SNPs that were in linkage disequilibrium (<i>r</i>² ≥ 0.2). Among those SNPs, associations with slow and non-progression towards AIDS are sought and replicated. Randomisations are carried out in order to evaluate the statistical robustness of our results. Finally, the genetic associations are used to link progression to AIDS and gene expression in candidate genes.</p

Image_1_The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control.jpeg

IntroductionWe have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers.MethodsWe performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region.ResultsOur analysis identified 2,626 SNPs significantly associated (pDiscussionThese findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control.</p