Reply to Huang et al.: Avoiding “one-size-fits-all” approaches to variant discovery

Huang et al. (1) argue that variant calling methods less conservative than GATK’s Best Practices workflow (2) increased false-positive variant discovery in our study of wild and cultivated potatoes (3), impacting diversity estimates. We disagree with their conclusion and highlight the rationale for the variant calling methods used in our study. First, GATK Best Practices, developed at the Broad Institute, were specifically designed and optimized for human genomics and medical research. Variant calling methodology for human medical research utilizes parameters and validation thresholds not intended for universal application across genomic studies. GATK’s hard filter is openly presented as a bias-prone substitute to their preferred (human-specific) variant quality … [↵][1]1To whom correspondence should be addressed. Email: buell{at}msu.edu. [1]: #xref-corresp-1-1

[1]  M. Morgante,et al.  Corn and humans: recombination and linkage disequilibrium in two genomes of similar size. , 2004, Trends in genetics : TIG.

[2]  D. Spooner,et al.  Genome diversity of the potato , 2018, Proceedings of the National Academy of Sciences.

[3]  Sarah Sandmann,et al.  Evaluating Variant Calling Tools for Non-Matched Next-Generation Sequencing Data , 2017, Scientific Reports.

[4]  Kui Lin,et al.  Genomic analyses provide insights into the history of tomato breeding , 2014, Nature Genetics.

[5]  A. Leitch,et al.  Genomic Plasticity and the Diversity of Polyploid Plants , 2008, Science.

[6]  Randall L. Nelson,et al.  Impacts of genetic bottlenecks on soybean genome diversity , 2006, Proceedings of the National Academy of Sciences.

[7]  Mauricio O. Carneiro,et al.  From FastQ Data to High‐Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline , 2013, Current protocols in bioinformatics.

[8]  Gary D Stormo,et al.  An Overview of RNA Sequence Analyses: Structure Prediction, ncRNA Gene Identification, and RNAi Design , 2013, Current protocols in bioinformatics.

[9]  Yuling Bai,et al.  Domestication and Breeding of Tomatoes: What have We Gained and What Can We Gain in the Future? , 2007, Annals of botany.

[10]  E. M. Farré,et al.  Genome diversity of tuber-bearing Solanum uncovers complex evolutionary history and targets of domestication in the cultivated potato , 2017, Proceedings of the National Academy of Sciences.

[11]  Insuk Lee,et al.  Systematic comparison of variant calling pipelines using gold standard personal exome variants , 2015, Scientific Reports.