What is a transcriptomic POD (tPOD) and how is it calculated?

The intial curve fitting and BMD calculation are done at the gene level (geneBMD). However, the main statistic of interest is usually the dose at which the whole-transcriptome is responding to chemical exposure, or the transcriptomic point-of-departure (tPOD). The NTP report defines the tPOD based on pathway enrichment analysis of the geneBMDs (see Pathway BMD Analysis for more details).

However, with many ecological species these pathway-based tPODs are unstable due to the low number of annotated gene sets compared to popular mammalian model organisms, and thus it has been proposed to estimate a statistical tPOD based on the distribution of geneBMDs. There are three different methods for estimating statistical tPODs in FastBMD:

  • tPOD20: the tPOD is equal to the 20th lowest geneBMD value
  • tPOD10th: the tPOD is equal to the 10th percentile of the geneBMD values
  • tPODmode: the tPOD is equal to the mode of the first peak in the distribution of geneBMD values