2-AIN-505, 2-AIN-251: Seminar in Bioinformatics (1), (3)
Winter 2021

Pay Giesselmann, Bjorn Brandl, Etienne Raimondeau, Rebecca Bowen, Christian Rohrandt, Rashmi Tandon, Helene Kretzmer, Gunter Assum, Christina Galonska, Reiner Siebert, Ole Ammerpohl, Andrew Heron, Susanne A. Schneider, Julia Ladewig, Philipp Koch, Bernhard M. Schuldt, James E. Graham, Alexander Meissner, Franz-Josef Muller. Analysis of short tandem repeat expansions and their methylation state withnanopore sequencing. Nature biotechnology, 37(12):1478-1481. 2019.

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Expansions of short tandem repeats are genetic variants that have been implicated
in several neuropsychiatric and other disorders, but their assessment remains
challenging with current polymerase-based methods(1-4). Here we introduce a
CRISPR-Cas-based enrichment strategy for nanopore sequencing combined with an
algorithm for raw signal analysis. Our method, termed STRique for short tandem
repeat identification, quantification and evaluation, integrates conventional
sequence mapping of nanopore reads with raw signal alignment for the localization
of repeat boundaries and a hidden Markov model-based repeat counting mechanism.
We demonstrate the precise quantification of repeat numbers in conjunction with
the determination of CpG methylation states in the repeat expansion and in
adjacent regions at the single-molecule level without amplification. Our method
enables the study of previously inaccessible genomic regions and their epigenetic