Discretized Gaussian mixture for genotyping of microsatellite loci containing homopolymer runs
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TLDR
GenoTan, a program using a discretized Gaussian mixture model combined with a rules-based approach to identify inherited variation of microsatellite loci from short sequence reads without paired-end information, effectively distinguishes length variants from noise including insertion/deletion errors in homopolymer runs by addressing the bidirectional aspect of insertion and deletion errors in sequence reads.Abstract:
Motivation: Inferring lengths of inherited microsatellite alleles with single base pair resolution from short sequence reads is challenging due to several sources of noise caused by the repetitive nature of microsatellites and the technologies used to generate raw sequence data. Results: We have developed a program, GenoTan, using a discretized Gaussian mixture model combined with a rules-based approach to identify inherited variation of microsatellite loci from short sequence reads without paired-end information. It effectively distinguishes length variants from noise including insertion/deletion errors in homopolymer runs by addressing the bidirectional aspect of insertion and deletion errors in sequence reads. Here we first introduce a homopolymer decomposition method which estimates error bias toward insertion or deletion in homopolymer sequence runs. Combining these approaches, GenoTan was able to genotype 94.9% of microsatellite loci accurately from simulated data with 40x sequence coverage quickly while the other programs showed590% correct calls for the same data and required 5� 30� more computational time than GenoTan. It also showed the highest true-positive rate for real data using mixed sequence data of two Drosophila inbred lines, which was a novel validation approach for genotyping. Availability: GenoTan is open-source software available at http://gen otan.sourceforge.net.read more
Citations
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Journal ArticleDOI
Abundance of ethnically biased microsatellites in human gene regions.
Nicholas A. Kinney,Lin Kang,Laurel Eckstrand,Arichanah Pulenthiran,Peter Samuel,Ramu Anandakrishnan,Robin T. Varghese,Pawel Michalak,Pawel Michalak,Pawel Michalak,Harold R. Garner +10 more
TL;DR: Investigation of genotype frequencies, functional relevance, and adaptive potential of microsatellites in five super-populations (ethnicities) drawn from the 1000 Genomes Project finds 3,984 ethnically-biased microsatellite loci (EBML).
Journal ArticleDOI
ZDHHC3 as a Risk and Mortality Marker for Breast Cancer in African American Women.
TL;DR: Investigating variations in microsatellite genomic regions—a type of repetitive DNA—and possible links to the breast cancer mortality gap finds that ZDHHC3 messenger RNA expression is significantly lower in African Americans compared with whites.
Posted ContentDOI
Detecting tandem repeat expansions in cohorts sequenced with short-read sequencing data
Rick M. Tankard,Mark F. Bennett,Peter Degorski,Martin B. Delatycki,Paul J. Lockhart,Melanie Bahlo +5 more
TL;DR: It is demonstrated that methods such as exSTRa can be effectively utilized as a screening tool to interrogate WES data generated with PCR-based library preparations and WGS data generated using either PCR- based or PCR-free library protocols, for repeat expansions which can then be followed up with specific diagnostic tests.
Book ChapterDOI
Assessment of Microsatellite Instability from Next-Generation Sequencing Data.
TL;DR: This chapter describes the different approaches developed for the assessment of MSI from NGS data in cancer, including the different microsatellite panels and computational algorithms proposed, highlighting their advantages and drawbacks, and their evaluation in different clinical applications.
Journal ArticleDOI
Exome-wide somatic microsatellite variation is altered in cells with DNA repair deficiencies.
TL;DR: It is shown that DNA instability can be identified in a sample and that patterns of instability vary depending on the impaired DNA repair mechanism, and that genes harboring minor alleles are strongly associated with cancer pathways.
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