RT Journal
A1 Smith, Tom
A1 Heger, Andreas
A1 Sudbery, Ian
T1 UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy
JF Genome Research 
JO Genome Research 
YR 2017 
FD March 01 
VO 27 
IS 3 
SP 491 
OP 499 
DO 10.1101/gr.209601.116 
UL http://genome.cshlp.org/content/27/3/491.abstract 
AB Unique Molecular Identifiers (UMIs) are random oligonucleotide barcodes that are increasingly used in high-throughput sequencing experiments. Through a UMI, identical copies arising from distinct molecules can be distinguished from those arising through PCR amplification of the same molecule. However, bioinformatic methods to leverage the information from UMIs have yet to be formalized. In particular, sequencing errors in the UMI sequence are often ignored or else resolved in an ad hoc manner. We show that errors in the UMI sequence are common and introduce network-based methods to account for these errors when identifying PCR duplicates. Using these methods, we demonstrate improved quantification accuracy both under simulated conditions and real iCLIP and single-cell RNA-seq data sets. Reproducibility between iCLIP replicates and single-cell RNA-seq clustering are both improved using our proposed network-based method, demonstrating the value of properly accounting for errors in UMIs. These methods are implemented in the open source UMI-tools software package.