Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications

摘要: High-throughput DNA sequencing technology has transformed genetic research and is starting to make an impact on clinical practice. However, analyzing high-throughput data remains challenging, particularly in settings where accuracy turnaround times are critical. We present a new approach this problem, implemented software package called Platypus. Platypus achieves high sensitivity specificity for SNPs, indels complex polymorphisms by using local de novo assembly generate candidate variants, followed realignment probabilistic haplotype estimation. It order of magnitude faster than existing tools generates calls from raw aligned read without preprocessing. demonstrate the performance clinically relevant experimental designs comparing with SAMtools GATK whole-genome exome-capture data, identifying variation 15 parent-offspring trios specificity, estimating human leukocyte antigen genotypes directly variant calls.