Panel of Normals Filter

Overview

A Panel of Normals (PoN) filter removes recurrent technical artifacts and germline variants that appear as apparent somatic calls across multiple samples. A set of normal (non-tumor) samples is genotyped at candidate somatic sites; positions that are recurrently called in the normal samples are flagged and removed from the somatic call set. This filter is highly effective at removing systematic sequencing and alignment artifacts.

Used by

• The Broad Panel of Normals v2 (broad_PoN_v2) was the single largest filter in the TCGA MC3 pipeline, removing ~30% of all called variants; identified as more effective than any individual caller-based filter at eliminating recurrent sequencing artifacts PMID:29596782
• Referenced as a validation-technology confounder: because validation used the same chemistry as discovery, PoN-filtered variants appearing in validation data can produce apparent “erroneous filtering” that is actually correct removal of artifacts PMID:29596782

Notes

• PoN size and composition affect sensitivity/specificity; larger and more diverse PoNs generally perform better.
• A limitation is that the normal panel cannot account for tumor-type-specific artifacts that are absent from the normals used.
• The Broad PoN v2 was specifically used in TCGA MC3; other versions may differ substantially in content.

Sources

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