@article {847, title = {Chromosome-scale, haplotype-resolved assembly of human genomes.}, journal = {Nat Biotechnol}, volume = {39}, year = {2021}, month = {2021 03}, pages = {309-312}, abstract = {

Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50\% of the known genome (NG50) up to 25 Mb and phased ~99.5\% of heterozygous sites at 98-99\% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.

}, keywords = {Algorithms, Chromosomes, Human, Genome, Human, Haplotypes, Heterozygote, Humans, Polymorphism, Single Nucleotide}, issn = {1546-1696}, doi = {10.1038/s41587-020-0711-0}, author = {Garg, Shilpa and Fungtammasan, Arkarachai and Carroll, Andrew and Chou, Mike and Schmitt, Anthony and Zhou, Xiang and Mac, Stephen and Peluso, Paul and Hatas, Emily and Ghurye, Jay and Maguire, Jared and Mahmoud, Medhat and Cheng, Haoyu and Heller, David and Zook, Justin M and Moemke, Tobias and Marschall, Tobias and Sedlazeck, Fritz J and Aach, John and Chin, Chen-Shan and Church, George M and Li, Heng} } @article {867, title = {Parliament2: Accurate structural variant calling at scale.}, journal = {Gigascience}, volume = {9}, year = {2020}, month = {2020 12 21}, abstract = {

BACKGROUND: Structural variants (SVs) are critical contributors to genetic diversity and genomic disease. To predict the phenotypic impact of SVs, there is a need for better estimates of both the occurrence and frequency of SVs, preferably from large, ethnically diverse cohorts. Thus, the current standard approach requires the use of short paired-end reads, which remain challenging to detect, especially at the scale of hundreds to thousands of samples.

FINDINGS: We present Parliament2, a consensus SV framework that leverages multiple best-in-class methods to identify high-quality SVs from short-read DNA sequence data at scale. Parliament2 incorporates pre-installed SV callers that are optimized for efficient execution in parallel to reduce the overall runtime and costs. We demonstrate the accuracy of Parliament2 when applied to data from NovaSeq and HiSeq X platforms with the Genome in a Bottle (GIAB) SV call set across all size classes. The reported quality score per SV is calibrated across different SV types and size classes. Parliament2 has the highest F1 score (74.27\%) measured across the independent gold standard from GIAB. We illustrate the compute performance by processing all 1000 Genomes samples (2,691 samples) in <1 day on GRCH38. Parliament2 improves the runtime performance of individual methods and is open source (https://github.com/slzarate/parliament2), and a Docker image, as well as a WDL implementation, is available.

CONCLUSION: Parliament2 provides both a highly accurate single-sample SV call set from short-read DNA sequence data and enables cost-efficient application over cloud or cluster environments, processing thousands of samples.

}, issn = {2047-217X}, doi = {10.1093/gigascience/giaa145}, author = {Zarate, Samantha and Carroll, Andrew and Mahmoud, Medhat and Krasheninina, Olga and Jun, Goo and Salerno, William J and Schatz, Michael C and Boerwinkle, Eric and Gibbs, Richard A and Sedlazeck, Fritz J} }