What is the impact of assay failure in your laboratory and how do you monitor for it? The most heavily degraded samples are not suitable for standard exome coverage: sometimes it’s not even a matter of getting bad sequencing, you might get nothing at all! FFPE artifacts increase with storage time Artifacts go against the statistical power of your variant calling analysis Molecular reference standards help filter out bad mappings and spurious variants Bioinformatics pipelines allow adding Molecular Reference Standards in your joint variant calling pipeline Genome In A Bottle Reference Standards are invaluable for validating variant calling analysis NIST and its collaborators shared datasets created with most NGS technologies Horizon Diagnostics shared annotated, merged variant calls from NIST for the Ashkenazim Trio ~35K variants are predicted having high or moderate impact within the Trio GM24385 (Ashkenazim Son) includes 352 small variants with high/moderate impact which are absent in Father and Mother Routinely monitor the performance of your workflows and assays with independent external controls