PEMapper and PECaller provide a simplified approach to whole-genome sequencing

Abstract

The analysis of human whole-genome sequencing data presents significant computational challenges. The sheer size of datasets places an enormous burden on computational, disk array, and network resources. Here, we present an integrated computational package, PEMapper/PECaller, that was designed specifically to minimize the burden on networks and disk arrays, create output files that are minimal in size, and run in a highly computationally efficient way, with the single goal of enabling whole-genome sequencing at scale. In addition to improved computational efficiency, we implement a statistical framework that allows for a base by base error model, allowing this package to perform as well or better than the widely used Genome Analysis Toolkit (GATK) in all key measures of performance on human whole-genome sequences.

A neurogenetic model for the study of schizophrenia spectrum disorders: the International 22q11.2 Deletion Syndrome Brain Behavior Consortium

“…69 Cleaned and annotated (reference genome assembly GRCh38) sequence data are placed into variant call format and annotated using ANNOVAR, 70 enabling standard analytic approaches to be applied, including variant classes (that is, exonic, intronic), rarity and functional effects. 71–73 Annotation of SNVs from coding regions uses standard pipelines and bioinformatic filters for functional impact.…”

Integrating Next-Generation Genomic Sequencing and Mass Spectrometry To Estimate Allele-Specific Protein Abundance in Human Brain

“…, sites that change the primary coding sequence), and 10,409 silent SNVs. Both cases had ~1:1 silent-to-replacement sites and a transition-to-transversion ratio of ~2.3 for the human whole exome, indicating good quality sequencing 33 . A PPD was constructed using GenPro for each sample (Figure 1) using the variant base calls.…”

“…Whole-exome sequencing was performed using the SeqCap EZ Exome v2 Human Exome Capture Kit (Roche, Switzerland) according to the manufacturer’s protocol, with 100-bp paired-end sequencing on an Illumina HiSeq 2000 instrument to an average read depth of 100X. Raw sequencing reads were mapped to the whole human genome (GRCh38) using the PEMapper and variant sites were identified using PECaller with a theta of 0.001 and probability to call a variant site of 95% within the approximately 32 million bases that constitute the consensus coding domain 33 .…”

“…The software generates the reference proteome through in silico in-frame translation of each transcript in the binary database (Supplementary Figure 1). To generate a PPD for a given sample, the software reads variants from either a VCF- or SNP-formatted file 33–34 , and creates all novel proteins for each missense SNV on a per sample basis. Each variant protein is then digested in silico with a user-specified protease and only if the variant protein results in one or more novel peptides ( i.e.…”

Bystro: rapid online variant annotation and natural-language filtering at whole-genome scale

“…Creating an annotation online is as simple as selecting the genome and assembly used to make the variant call format (VCF) [9] or SNP [10] format files, and uploading these files from a computer or Amazon S3 bucket, which can be easily linked to the web application. Annotation occurs in the cloud, where distributed instances of the Bystro annotation engine process the data and send the results back to the web application for storage and display (Figure 1).…”