Dante: genotyping of known complex and expanded short tandem repeats

Budiš, Jaroslav; Kucharík, Marcel; Ďuriš, František; Gazdarica, Juraj; Zrubcová, Michaela; Ficek, Andrej; Szemes, Tomáš; Brejová, Broňa; Radvánszky, Ján

doi:10.1093/bioinformatics/bty791

Cited by 17 publications

(18 citation statements)

References 30 publications

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“…The exSTRa program is a new option which is more appropriate for detection of repeat expansion disorders [66]. Additional options include STRetch [67], TREDPARSE [68], and Dante [69].…”

Section: Methodsmentioning

confidence: 99%

Abundance of ethnically biased microsatellites in human gene regions

et al. 2019

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Microsatellites–a type of short tandem repeat (STR)–have been used for decades as putatively neutral markers to study the genetic structure of diverse human populations. However, recent studies have demonstrated that some microsatellites contribute to gene expression, cis heritability, and phenotype. As a corollary, some microsatellites may contribute to differential gene expression and RNA/protein structure stability in distinct human populations. To test this hypothesis, we investigate genotype frequencies, functional relevance, and adaptive potential of microsatellites in five super-populations (ethnicities) drawn from the 1000 Genomes Project. We discover 3,984 ethnically-biased microsatellite loci (EBML); for each EBML at least one ethnicity has genotype frequencies statistically different from the remaining four. South Asian, East Asian, European, and American EBML show significant overlap; on the contrary, the set of African EBML is mostly unique. We cross-reference the 3,984 EBML with 2,060 previously identified expression STRs (eSTRs); repeats known to affect gene expression (64 total) are over-represented. The most significant pathway enrichments are those associated with the matrisome: a broad collection of genes encoding the extracellular matrix and its associated proteins. At least 14 of the EBML have established links to human disease. Analysis of the 3,984 EBML with respect to known selective sweep regions in the genome shows that allelic variation in some of them is likely associated with adaptive evolution.

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“…The exSTRa program is a new option which is more appropriate for detection of repeat expansion disorders [66]. Additional options include STRetch [67], TREDPARSE [68], and Dante [69].…”

Section: Methodsmentioning

confidence: 99%

Abundance of ethnically biased microsatellites in human gene regions

et al. 2019

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“…Galaxy environment has a STR analysis tool called STR-FM which we were unable to run (Fungtammasan et al, 2015). Dante (Budiš et al, 2019) and STRScan (Tang, Haixu et al, 2017) are designed for targeted searches and requires a user-defined list of STR loci.…”

Section: Introductionmentioning

confidence: 99%

Accuracy of short tandem repeats genotyping tools in whole exome sequencing data

Halman

Oshlack

2020

Preprint

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Background: Short tandem repeats are important source of genetic variation, they are highly mutable and repeat expansions are associated dozens of human disorders, such as Huntington's disease and spinocerebellar ataxias. Technical advantages in sequencing technology have made it possible to analyse these repeats at large scale, however, accurate genotyping is still a challenging task. We compared four different short tandem repeats genotyping tools on whole exome sequencing data to determine their genotyping performance and limits which will aid other researchers to choose a suitable tool and parameters for analysis. Methods:The analysis was performed on the Simons Simplex Collection dataset where we used a novel method of evaluation with accuracy determined by the rate of homozygous calls on the X chromosome of male samples. In total we analysed 433 samples and around a million genotypes for evaluating tools on whole exome sequencing data. Results:We determined a relatively good performance of all tools when genotyping repeats of 3-6 bp in length which could be improved with coverage and quality score filtering. However, genotyping homopolymers was challenging for all tools and a high error rate was present across different thresholds of coverage and quality scores. Interestingly, dinucleotide repeats displayed a high error rate as well, which was found to be mainly caused by the AC/TG repeats. Overall, LobSTR was able to make the most calls and was also the fastest tool while RepeatSeq and HipSTR exhibited the lowest heterozygous error rate at low coverage. Conclusions:All tools have different strengths and weaknesses and the choice may depend on the type of analysis. In this analysis we demonstrated the effect of using different filtering parameters and offered recommendations based on the trade-off between the best accuracy of genotyping and the highest number of calls.

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“…Testing is focused mainly on identifying an additional copy of a chromosome, the condition called trisomy [2], represented as an excessive proportion of genomic material from the aberrant chromosome. Discovery of fetal DNA fragments in plasma extracted from maternal blood, cell-free fetal DNA (cffDNA) [3], opened up new options in the field of prenatal screening called non-invasive prenatal testing (NIPT) [1,4]. In contrast to established screening methods [5], sampling of genetic material from the mother’s circulation does not pose any direct risk for the fetus [6].…”

Section: Introductionmentioning

confidence: 99%

Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing

Gazdarica

Hekel

Budiš

et al. 2019

IJMS

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The reliability of non-invasive prenatal testing is highly dependent on accurate estimation of fetal fraction. Several methods have been proposed up to date, utilizing different attributes of analyzed genomic material, for example length and genomic location of sequenced DNA fragments. These two sources of information are relatively unrelated, but so far, there have been no published attempts to combine them to get an improved predictor. We collected 2454 single euploid male fetus samples from women undergoing NIPT testing. Fetal fractions were calculated using several proposed predictors and the state-of-the-art SeqFF method. Predictions were compared with the reference Y-based method. We demonstrate that prediction based on length of sequenced DNA fragments may achieve nearly the same precision as the state-of-the-art methods based on their genomic locations. We also show that combination of several sample attributes leads to a predictor that has superior prediction accuracy over any single approach. Finally, appropriate weighting of samples in the training process may achieve higher accuracy for samples with low fetal fraction and so allow more reliability for subsequent testing for genomic aberrations. We propose several improvements in fetal fraction estimation with a special focus on the samples most prone to wrong conclusion.

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Dante: genotyping of known complex and expanded short tandem repeats

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 17 publications

References 30 publications

Abundance of ethnically biased microsatellites in human gene regions

Abundance of ethnically biased microsatellites in human gene regions

Accuracy of short tandem repeats genotyping tools in whole exome sequencing data

Combination of Fetal Fraction Estimators Based on Fragment Lengths and Fragment Counts in Non-Invasive Prenatal Testing

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