Crowdsourced direct-to-consumer genomic analysis of a family quartet

Corpas, Manuel; Valdivia-Granda, Willy; Torres, Nazareth; Greshake, Bastian; Coletta, Alain; Knaus, Alexej; Harrison, Andrew; Cariaso, Mike; Morán, Federico; Nielsen, Fiona; Swan, Daniel; Solis, David; Krawitz, Peter; Schacherer, Frank; Schols, Peter; Yang, Huangming; Borry, Pascal; Glusman, Gustavo; Robinson, Peter N.

doi:10.1186/s12864-015-1973-7

Cited by 20 publications

(29 citation statements)

References 44 publications

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“…Such considerations absolutely do not negate the enormous potential for applying genomics in a public health context-but they do imply that a signifi cant measure of caution should be applied as we pursue this exciting prospect. It is clear that at present we do not know how to interpret the results of genome-scale sequencing in the healthy population; our inability to reliably assign pathogenicity to variants, the tendency toward overinterpretation, misinterpretation, and our simple lack of knowledge about the natural history of most genetic disorders argue convincingly that it is premature to implement genome-scale sequencing in healthy individuals outside the realm of research [3,[37][38][39][40]. However, we do have a reasonably solid grasp of what the implications are for individuals who carry a pathogenic variation in a few of the approximately 22,000 human genes.…”

Section: Resultsmentioning

confidence: 99%

A Proposed Approach for Implementing Genomics-Based Screening Programs for Healthy Adults

et al. 2018

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This paper is a product of a working group of the Genomics and Population Health Action Collaborative, an ad hoc activity of the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine. The paper should not be viewed as a consensus statement of the Action Collaborative or Roundtable. The paper and the conclusions it draws are the individual opinions of the listed authors.

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Section: Resultsmentioning

confidence: 99%

A Proposed Approach for Implementing Genomics-Based Screening Programs for Healthy Adults

et al. 2018

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“…Motif discovery analyses were performed on Orion Integrated Biosciences servers using MF generation (MF-gen) and CHAST algorithms to identify protein fragments associated with precise taxonomies via an exhaustive search of GenBank protein databases as described in Corpas et al (58) and Wilson et al (36). Briefly, all protein entries in GenBank were divided into 12-amino acid subsequences (motifs) that were position-independent and did not contain overlaps.…”

Section: Methodsmentioning

confidence: 99%

Clustering of Vibrio parahaemolyticus Isolates Using MLST and Whole-Genome Phylogenetics and Protein Motif Fingerprinting

Jesser

Valdivia-Granda

Jones

et al. 2019

Front. Public Health

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Vibrio parahaemolyticus is a ubiquitous and abundant member of native microbial assemblages in coastal waters and shellfish. Though V. parahaemolyticus is predominantly environmental, some strains have infected human hosts and caused outbreaks of seafood-related gastroenteritis. In order to understand differences among clinical and environmental V. parahaemolyticus strains, we used high quality DNA sequencing data to compare the genomes of V. parahaemolyticus isolates ( n = 43) from a variety of geographic locations and clinical and environmental sample matrices. We used phylogenetic trees inferred from multilocus sequence typing (MLST) and whole-genome (WG) alignments, as well as a novel classification and genome clustering approach that relies on protein motif fingerprints (MFs), to assess relationships between V. parahaemolyticus strains and identify novel molecular targets associated with virulence. Differences in strain clustering at more than one position were observed between the MLST and WG phylogenetic trees. The WG phylogeny had higher support values and strain resolution since isolates of the same sequence type could be differentiated. The MF analysis revealed groups of protein motifs that were associated with the pathogenic MLST type ST36 and a large group of clinical strains isolated from human stool. A subset of the stool and ST36-associated protein motifs were selected for further analysis and the motif sequences were found in genes with a variety of functions, including transposases, secretion system components and effectors, and hypothetical proteins. DNA sequences associated with these protein motifs are candidate targets for future molecular assays in order to improve surveys of pathogenic V. parahaemolyticus in the environment and seafood.

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“…We performed this procedure for four "real-world" trios with publicly available exome data: the Ashkenazim trio HG002_NA24385 from the Genome in the Bottle project [13] ("AJT"), the YRI_NA19240 trio from the 1000 Genomes project [14] ("YRI"), the CHD trio [15] ("CHD"), and the Corpas family daughter trio [16] ("Corpas"). Since the child in the "real-world" trios was either a living individual (AJT, YRI, Corpas) or stillborn (CHD), there was no maternal cell contamination in the "real-world" reads.…”

Section: Contaminated Trio Generationmentioning

confidence: 99%

Accurate fetal variant calling in the presence of maternal cell contamination

Nabieva

Sharma

Kapushev

et al. 2019

Preprint

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AbstractHigh-throughput sequencing of fetal DNA is a promising and increasingly common method for the discovery of all (or all coding) genetic variants in the fetus, either as part of prenatal screening or diagnosis, or for genetic diagnosis of spontaneous abortions. In many cases, the fetal DNA (from chorionic villi, amniotic fluid, or abortive tissue) can be contaminated with maternal cells, resulting in the mixture of fetal and maternal DNA. This maternal cell contamination (MCC) undermines the assumption, made by traditional variant callers, that each allele in a heterozygous site is covered, on average, by 50% of the reads, and therefore can lead to erroneous genotype calls. We present a panel of methods for reducing the genotyping error in the presence of MCC. All methods start with the output of GATK HaplotypeCaller on the sequencing data for the (contaminated) fetal sample and both of its parents, and additionally rely on information about the MCC fraction (which itself is readily estimated from the high-throughput sequencing data). The first of these methods uses a Bayesian probabilistic model to correct the fetal genotype calls produced by MCC-unaware HaplotypeCaller. The other two methods “learn” the genotype-correction model from examples. We use simulated contaminated fetal data to train and test the models. Using the test sets, we show that all three methods lead to substantially improved accuracy when compared with the original MCC-unaware HaplotypeCaller calls. We then apply the best-performing method to three chorionic villus samples from spontaneously terminated pregnancies.Code and training data availabilityhttps://github.com/bazykinlab/ML-maternal-cell-contamination

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Crowdsourced direct-to-consumer genomic analysis of a family quartet

Cited by 20 publications

References 44 publications

A Proposed Approach for Implementing Genomics-Based Screening Programs for Healthy Adults

A Proposed Approach for Implementing Genomics-Based Screening Programs for Healthy Adults

Clustering of Vibrio parahaemolyticus Isolates Using MLST and Whole-Genome Phylogenetics and Protein Motif Fingerprinting

Accurate fetal variant calling in the presence of maternal cell contamination

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