Mutation Burden Distribution

Over the past 20 years, advances in genomic sequencing technology have improved data resolution from bulk sequencing to the level of individual cells. While such data, especially relating to somatic mutations, has repeatedly revealed previously-immeasurable tumour histories, there is a need to merge the information provided by bulk (population-level) and single-cell data. Here, we developed a general framework to unite different statistical properties between bulk sequencing data and single-cell data: the site frequency spectra (SFS) from bulk data, division distributions (DD) and single-cell mutational burden distributions (MBD) from single-cell data.

The theoretical framework set forth by Dr Stark with C. Morison and Dr Huang is a crucial step towards better analytical understanding of distributions obtainable from single-cell data. Their work presents an example of applying mathematical ideas previously used to understand the population genetics of bulk data to the context of single-cell information, a trend which will increase in frequency as experimental applications and validation opportunities develop with the progression of sequencing technology.

Example birth-death process with numbers of mutations