BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Anders Ståhlberg & Serik Sagitov (Chalmers & University of Gothen burg) DTSTART:20221006T131500Z DTEND:20221006T140000Z DTSTAMP:20260422T155019Z UID:gbgstats/2 DESCRIPTION:Title: Counting molecular identifiers in sequencing using a multitype branching process with immigration\nby Anders Ståhlberg & Serik Sagitov (Chalme rs & University of Gothenburg) as part of Gothenburg statistics seminar\n\ nLecture held in MVL14.\n\nAbstract\nDetection of extremely rare variant a lleles\, such as tumour DNA\, within a complex mixture of DNA molecules is experimentally challenging due to sequencing errors. Barcoding of target DNA molecules in library construction for next-generation sequencing provi des a way to identify and bioinformatically remove polymerase induced erro rs. During the barcoding procedure involving $t$ consecutive PCR cycles\, the DNA molecules become barcoded by unique molecular identifiers (UMI). D ifferent library construction protocols utilise different values of $t$. T he effect of a larger $t$ and imperfect PCR amplifications is poorly descr ibed. \n\nThis paper proposes a branching process with growing immigration as a model describing the random outcome of $t$ cycles of PCR barcoding . Our model discriminates between five different amplification rates $r_1$ \, $r_2$\, $r_3$\, $r_4$\, $r$ for different types of molecules associated with the PCR barcoding procedure. We study this model by focussing on $C_ t$\, the number of clusters of molecules sharing the same \nUMI\, as well as $C_t(m)$\, the number of UMI clusters of size $m$. Our main finding i s a remarkable asymptotic pattern valid for moderately large $t$. It turns out that \n$E(C_t(m))/E(C_t)\\approx 2^{-m}$ for $m=1\,2\,\\ldots$\, rega rdless of the underlying parameters $(r_1\,r_2\,r_3\,r_4\,r)$. The knowled ge of the quantities $C_t$ and $C_t(m)$ as functions of the experimental p arameters $t$ and $(r_1\,r_2\,r_3\,r_4\,r)$ will help the users to draw mo re adequate conclusions from the outcomes of different sequencing protocol s.\n LOCATION:https://researchseminars.org/talk/gbgstats/2/ END:VEVENT END:VCALENDAR