Bioinformatics Seminars

Bioinformatics Seminar

Time:
Venue: Na

2 February 2016

Na

Detecting repeat expansions in massively parallel sequencing with a focus on ataxias

Rick Tankard
WEHI Population Health & Immunity Division

Expansions of short-tandem repeats (STR) in humans are responsible for over twenty neurological Mendelian disorders including spinocerebellar ataxias ; intellectual disabilities ; epilepsies and Huntington's disease. Current methods of analysing massively parallel sequencing (MPS) for STR size are focused on genotyping alleles that are smaller than read-fragment size ; whereas pathogenic STR expansions can be larger than the fragment size ; thus methods are needed to detect pathogenic sized STRs.

In this third year PhD review seminar ; I will describe attempts to build a statistical classifier based on aligned reads that allows discovery of expansions at STR loci not associated with the disease. Around known STR loci ; we find reads in paired-end data that may have their mate within the STR ; then detect that STR within the mate to determine that read's position relative to the STR of the sample. As we are interested in expanded alleles rather than sizing the allele ; we can make use of reads that have the STR on the read start and end unlike other popular STR algorithms such as lobSTR. We are still working on an adequate classifier. I will describe my pipeline to retrieve the data that we intend to use for the analysis and show some preliminary analysis on WGS data.

If time permits I will also briefly discuss a spinocerebellar ataxia family that was found to have a likely causative duplication and deletion outside of the linkage region that was previously published.




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