RT Journal Article
SR Electronic
T1 Short Tandem Repeat stutter model inferred from direct measurement of in vitro stutter noise
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 065110
DO 10.1101/065110
A1 Ofir Raz
A1 Tamir Biezuner
A1 Adam Spiro
A1 Shiran Amir
A1 Lilach Milo
A1 Alon Titelman
A1 Amos Onn
A1 Uriel Feige
A1 Ehud Shapiro
YR 2016
UL http://biorxiv.org/content/early/2016/07/21/065110.abstract
AB Short tandem repeats (STRs) are polymorphic genomic loci valuable for various applications such as research, diagnostics and forensics. However, their polymorphic nature acts as a double-edged sword, as during in vitro amplification STRs undergo mutational processes that cause stutter noise, especially in the shorter, more mutable, repeat types. Although it is possible to overcome stutter noise by using amplification-free library preparation, such protocols are presently incompatible with single cell analysis and with known targeted-enrichment protocols. To address this challenge, we have designed a method for direct measurement of in vitro noise. Using a synthetic STR sequencing library, we have calibrated a proposed Markov model for the prediction of stutter patterns at any amplification cycle. By employing this model, we have managed to genotype accurately even cases of severe amplification noise, where as little as 3% of the reads accurately reflect the original STR size.