Explore the types of human genomic variation and the diseases known to be caused by structural variants.
Explore how long-read sequencing enables solving of rare and mendelian diseases.
In this video, PacBio scientists present ongoing improvements to the Integrative Genomics Viewer (IGV) and demonstrate how multiple new features improve visualization support for PacBio long-read sequencing data. The video describes these recent updates which include; quick consensus accuracy mode to hide random single-molecule errors, direct phasing of haplotypes using long-read evidence, and visual annotation of insertions and deletions relative to the reference with enumeration of gap size for individual reads. These new features are available now in the development version of IGV, which can be found at http://software.broadinstitute.org/software/igv/download_snapshot. The Sequel sequencing data used in this demonstration is also publicly…
PacBio bioinformatician Aaron Wenger presents this ASHG 2016 poster demonstrating human structural variation detection at varying coverage levels with SMRT Sequencing on the Sequel System. Results were compared to truth sets for well-characterized genomes. Results indicate that even low coverage of SMRT Sequencing makes it possible to detect hundreds of SVs that are missed in high-coverage short-read sequencing data.
In this video Aaron Wenger describes the new structural variant detection application, known as pbsv, available in SMRT Link v5.0. This application identifies large (default: =50 bp) insertions and deletions in a sample relative to a reference from whole genome sequence data. Aaron details pbsv commands and use of the application in SMRT Link.
Explore human genetic variation and learn how SMRT Sequencing uncovers the full spectrum of structural variation to advance understanding of genetic disease and broaden our knowledge of human diversity.
Most of the basepairs that differ between two human genomes are in intermediate-sized structural variants (50 bp to 5 kb), which are too small to detect with array CGH but too large to reliably discover with short-read NGS. PacBio Single Molecule, Real-Time (SMRT) Sequencing fills this technology gap. SMRT Sequencing detects tens of thousands of structural variants in a human genome, approximately five times the sensitivity of short-read NGS. To discover variants using SMRT Sequencing, we have developed pbsv, which is available in version 5 of the PacBio SMRT Link software suite. The pbsv algorithm applies a sequence of stages:…
In this ASHG 2017 presentation, Jonas Korlach, the CSO of PacBio shared updates on three applications featuring SMRT Sequencing on the Sequel System, highlighting structural variant detection, targeted sequencing and the Iso-Seq method of RNA sequencing. He provided details on structural variant calling using pbsv to call insertions and deletions and compared PacBio variant calling with other technologies. Korlach described how targeted sequencing can be used to interrogate repeat expansions, detect and phase minor variants and can access medically relevant but previously inaccessible gene targets. He presented research featuring the Iso-Seq method that identified isoforms, corrected previous isoform annotations and…
In this ASHG 2017 presentation, Han Brunner of Radboud University Medical Center presented research using SMRT Sequencing to detect structural variants to uncover the genetic causes of intellectual disability. He shared that long-read sequencing enabled detection of 25,000 structural variants per genome. Brunner presented data from patient trios to identify de novo structural variant candidates and ongoing validation work to determine the causative mutations of intellectual disability.
In this ASHG 2017 presentation, Charles Lee of The Jackson Laboratory for Genomic Medicine presented work from the Human Genome Structural Variation Consortium. He shared data from efforts to utilize multiple platforms for the comprehensive discovery of structural variations—including insertions, deletions, inversions and mobile element insertions—in individual genomes. By combining various technologies, this research identified 7 times more structural variation per person than was previously known to exist.
In this video, Aaron Wenger, a research scientist at PacBio, describes the use of long-read SMRT Sequencing to detect structural variants in the human genome. He shares that structural variations – such as insertions and deletions – impact human traits, cause disease, and differentiate humans from other species. Wenger highlights the use of SMRT Sequencing and structural variant calling software tools in a collaboration with Stanford University which identified a disease-causing genetic mutation.
In this ASHG workshop presentation, Janet Song of Stanford School of Medicine shared research on resolving a tandem repeat array implicated in bipolar disorder and schizophrenia. These psychiatric diseases share a number of genomic risk variants, she noted, but scientists continue to search for a specific causal variant in the CACNA1C gene suggested by previous genome-wide association studies. SMRT Sequencing of this region in 16 individuals identified a series of 30-mer repeats, containing a total of about 50 variants. Analysis showed that 10 variants were linked to protective or risk haplotypes. Song aims to study the function of these variants…
Each human genome has thousands of structural variants compared to the reference assembly, up to 85% of which are difficult or impossible to detect with Illumina short reads and are only visible with long, multi-kilobase reads. The PacBio RS II and Sequel single molecule, real-time (SMRT) sequencing platforms have made it practical to generate long reads at high throughput. These platforms enable the discovery of structural variants just as short-read platforms did for single nucleotide variants. Numerous software algorithms call structural variants effectively from PacBio long reads, but algorithm sensitivity is lower for insertion variants and all heterozygous variants. Furthermore,…
Despite amazing progress over the past quarter century in the technology to detect genetic variants, intermediate-sized structural variants (50 bp to 50 kb) have remained difficult to identify. Such variants are too small to detect with array comparative genomic hybridization, but too large to reliably discover with short-read DNA sequencing. Recent de novo assemblies of human genomes have demonstrated the power of PacBio Single Molecule, Real-Time (SMRT) Sequencing to fill this technology gap and sensitively identify structural variants in the human genome. While de novo assembly is the ideal method to identify variants in a genome, it requires high depth…
Structural variants (genomic differences =50 base pairs) contribute to the evolution of organisms traits and human disease. Most structural variants (SVs) are too small to detect with array comparative genomic hybridization but too large to reliably discover with short-read DNA sequencing. Recent studies in human genomes show that PacBio SMRT Sequencing sensitively detects structural variants.