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Chunk #39 — METHODS — Anomaly detection and quality control

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Detectable clonal mosaicism from birth to old age and its relationship to cancer.
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In the BAF method, Circular Binary Segmentation (CBS)49 was used to detect change points in a metric modified from Itsara et al.15: sqrt(min(BAF,1-BAF,|BAF -median(BAF)|)) for SNPs called as missing or heterozygotes (i.e. excluding homozygotes). The use of missing calls allows detection of wide splits (e.g. Figure 3d). In the LOH method, CBS was applied to LRR values and combined with overlapping runs of homozygosity. By focusing on regions of homozygosity, we avoided a high false positive rate associated with a genome-wide search for changes in LRR. In both methods, the identification of anomalous segments involved establishing a non-anomalous baseline, choosing anomalous segments based on deviation from baseline, and applying quality control filters. Computations were done using the Bioconductor packages DNACopy and GWASTools. The latter was developed by our group; relevant functions are described in the Supplementary Note.