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.
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