Breakdown of no-calls made by SGZ.

<p>Reasons behind no-calls made by SGZ are shown for (left) all variants in 30 lung and colon samples and (right) 17 somatic hotspot mutations and 20 common germline variants within 20,182 clinical samples.</p

Likely somatic status mis-annotation in COSMIC, predicted by SGZ to be germline in multiple samples in Foundation Medicine sample set^†.

<p>Likely somatic status mis-annotation in COSMIC, predicted by SGZ to be germline in multiple samples in Foundation Medicine sample set<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005965#t004fn001" target="_blank">^†</a>.</p

Copy number detection overview.

<p>Aligned DNA sequences of the tumor specimen are normalized against a process‐matched normal, producing log‐ratio and minor allele frequency (MAF) data. Next, whole‐genome segmentation is performed using a circular binary segmentation (CBS) algorithm on the log‐ratio data. Then, a Gibbs sampler fitted copy number model and a grid‐based model are fit to the segmented log‐ratio and MAF data, producing genome‐wide copy number estimates. Finally, the degree of fit of candidate models returned by Gibbs sampling and grid sampling are compared and the optimal model is selected by an automated heuristic.</p

SGZ performance as a function of tumor purity in the cell line dataset.

<p>SGZ performance as a function of tumor purity in the cell line dataset.</p

Tumor zygosity predictions of somatic mutations in 20,182 clinical samples.

<p>Tumor zygosity predictions of somatic mutations in 20,182 clinical samples.</p

SGZ method overview.

<p>The SGZ pipeline is overviewed in panel A. Key components include fitting an optimal copy number model to the genome‐wide log‐ratio and minor allele frequency profiles (B), and modeling the expected allele frequencies of germline, somatic, and subclonal somatic mutations (C). In panel B, the dots in the top panel correspond to log ratios at each exon sequenced, segmented and fitted to discrete copy number levels, while the dots on the bottom panel are germline SNP minor allele frequencies. In panel C, examples of expected variant allele frequencies are shown for various scenarios of copy number and tumor purity. The expected allele frequencies are shown for germline (blue), somatic (red), and subclonal somatic (yellow).</p

Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome - Fig 1

<p><b>Study cohort overview</b> A) Tabulation of Children’s Oncology Group (COG) risk classification and treatment time points of biopsy for 151 samples. (Intermed. = intermediate risk group) B) Number of samples taken at each treatment time point for nine patients with serial biopsies. (HR = high risk, IR = intermediate risk, LR = low risk at time of biopsy; further information in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006501#pgen.1006501.s003" target="_blank">S2 Table</a>) C) Tabulation of all variants identified (VUS: variants of unknown significance) D) Total number of variants identified per sample, stratified by COG risk group. Inset shows a similar calculation for suspected driver variants only. Heavy line represents the median of the data. “n” indicates the number of patients in each risk group. E) Total number of variants in each sample. Each bar represents an individual sample; color corresponds to risk group (red = high, blue = intermediate, green = low).</p

Genetic variants from a single patient at different treatment time points.

<p>Each biopsy was at a different anatomic site. Red denotes suspected driver variants; gray denotes variants of unknown significance. Letter preceding tumor location indicates primary (P) or metastatic (M) site. Number in parentheses indicates inferred allelic fraction for mutation calls, or inferred copy number for amplification or deletion calls. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006501#pgen.1006501.s003" target="_blank">S2 Table</a> for additional details. Note that this patient was treated with crizotinib following the 5^th relapse.</p