PMC

Pipeline for WGS Variant Identification. WGS produces ~4 million variants per genome and requires extensive filtering to identify variants of interest. Shown here is a potential pipeline to identify variants. The first pass of the pipeline entails only reviewing variants in the coding regions of genes of interest and filtering by frequency, protein pathogenicity, and mode of inheritance (segregation in available family members). If no variant is identified, a second pass includes the same filtering steps, but on variants in all coding regions. The third pass includes analysis of non-coding variation using frequency, conservation and ENCODE annotation, along with mode of inheritance. The complexity of analysis increases with each pass.

Size and Cost Considerations of Next-Generation Sequencing. (A) The amount of data generated by a typical cardiomyopathy gene panel of ~50 genes (green), whole exome sequencing (red) and whole genome Sequencing (blue) is shown; (B) The approximate number of variants produced by each method is indicated; (C) The Clinical cost of each method ranges from ~$4000 (cardiomyopathy gene panel, green) to ~$9500 (whole genome sequencing, blue); (D) The cost per variant is greatly reduced for WGS ($0.002, blue) versus WES ($0.08, red) and gene panel-based sequencing ($1.70, green). Boxes indicate parameters used to calculate values in A–D including coverage, base pairs interrogated and total output.