Analytical “Bake-Off” of Whole Genome Sequencing Quality for the Genome Russia Project Using a Small Cohort for Autoimmune Hepatitis

A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight American patients afflicted with autoimmune hepatitis (AIH), plus one case’s unaffected parents, in a prelude to discovering genetic influences in this rare disease of unknown etiology. The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (FTCD), plus multiple occurrences of known HLA-DRB1 alleles associated with AIH (HLA-DRB1-03:01:01, 13:01:01 and 7:01:01). We also list putative SNVs in other genes as suggestive in AIH influence

Analytical “bake-off” of whole genome sequencing quality for the Genome Russia project using a small cohort for autoimmune hepatitis

<div><p>A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects. We assessed calling of SNPs, indels, copy number variation, and the speed of WGS throughput promised. Twenty separate QC analyses showed high similarities among the sequence quality and called genotypes. The ten genomes tested by the centers included eight American patients afflicted with autoimmune hepatitis (AIH), plus one case’s unaffected parents, in a prelude to discovering genetic influences in this rare disease of unknown etiology. The detailed internal replication and parallel analyses allowed the observation of two of eight AIH cases carrying a rare allele genotype for a previously described AIH-associated gene (<i>FTCD</i>), plus multiple occurrences of known <i>HLA-DRB1</i> alleles associated with AIH <i>(HLA-DRB1-03</i>:<i>01</i>:<i>01</i>, <i>13</i>:<i>01</i>:<i>01 and 7</i>:<i>01</i>:<i>01</i>). We also list putative SNVs in other genes as suggestive in AIH influence.</p></div

Raw read quality control parameters.

<p>Raw sequence read QC parameters are shown for three sequencing centers (colored differently).</p

Sample description.

<p>Sample description.</p

<i>HLA-DRB1</i> and <i>FTCD</i> genotypes.

<p><i>HLA-DRB1</i> and <i>FTCD</i> genotypes.</p

Genotype comparison.

<p>(A) Concordance of WGS genotypes with microarray genotypes. The concordance was estimated based on the trio data as the ratio of microarray SNPs with identical genotypes in WGS results. (B) Comparison of the three WGS datasets between each other in terms of precision, sensitivity and F-measure for pairwise comparisons. Color legend is given on the top right. (C) Concordance of genotypes in the three WGS datasets for all variants, SNPs and indels. Color legend is given on the top right.</p

Comparison of sequencing results (N = 17 parameters).

<p>Comparison of sequencing results (N = 17 parameters).</p

The ALICE Transition Radiation Detector: construction, operation, and performance

The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/ c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection