sonicLength - Estimating Abundance of Clones from DNA Fragmentation Data
Estimate the abundance of cell clones from the
distribution of lengths of DNA fragments (as created by
sonication, whence `sonicLength'). The algorithm in
"Estimating abundances of retroviral insertion sites from DNA
fragment length data" by Berry CC, Gillet NA, Melamed A,
Gormley N, Bangham CR, Bushman FD. Bioinformatics; 2012 Mar
15;28(6):755-62 is implemented. The experimental setting and
estimation details are described in detail there. Briefly,
integration of new DNA in a host genome (due to retroviral
infection or gene therapy) can be tracked using DNA sequencing,
potentially allowing characterization of the abundance of
individual cell clones bearing distinct integration sites. The
locations of integration sites can be determined by fragmenting
the host DNA (via sonication or fragmentase), breaking the
newly integrated DNA at a known sequence, amplifying the
fragments containing both host and integrated DNA, sequencing
those amplicons, then mapping the host sequences to positions
on the reference genome. The relative number of fragments
containing a given position in the host genome estimates the
relative abundance of cells hosting the corresponding
integration site, but that number is not available and the
count of amplicons per fragment varies widely. However, the
expected number of distinct fragment lengths is a function of
the abundance of cells hosting an integration site at a given
position and a certain nuisance parameter. The algorithm
implicitly estimates that function to estimate the relative
abundance.
