The challenge of hidden heritability
The advent of low-cost sequencing has provided a deeper understanding of the role human genetic variation plays in health and disease. However, due to the limitations of short-read technologies, most studies only report single nucleotide variants (SNVs) and small indel events, and miss larger structural variants and other complex genomic elements1. Non-SNV DNA variation accounts for 74% of all variant bases in the human genome2, and may be critical to uncovering the relationship of disease phenotypes to underlying genotypes.
Single Molecule, Real-Time (SMRT) Sequencing provides full access to human genomic variation through unmatched read lengths, uniform coverage, and exceptional accuracy. PacBio’s long single-molecule reads reveal previously hidden structural variants and produce direct variant phasing information across haplotype blocks. With the PacBio Systems, scientists gain new insight into the genetic basis of disease heritability.
Discover how SMRT Sequencing can impact human biomedical research
- Broaden the utility of precision medicine efforts to improve human health by including structural variation and allelic diversity in study designs
- Advance immune-disease association studies through imputation-free characterization of complex genes and haplotypes
- Drive cancer discovery with access to a more complete genomic cancer landscape
- Characterize pathogens, their mobile elements, host-interactions, communities, and origins to discover and design better vaccines, treatments, and outcomes
- Discover and understand causative biological mechanisms of neurological disease
PacBio long-read sequencing solutions for human biomedical research
- Accurately target and characterize complex regions underlying genetic disease
- Resolve structural variation across the complete size spectrum with base-pair resolution
- Unlock isoform diversity with full-length transcript and transcriptome sequencing
- Investigate pathogenicity, evolution, and selection with sensitive haplotyping of low-frequency viral and somatic variants
- Create gold-standard references unique to a population, disease, or individual
Structural Variation Project Calculator
Tell us about your structural variation sequencing project and receive an estimate on the time and materials needed to perform it on the Sequel System.
References
Selected Resources
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- Wenzel, Andrea et al. (2018) Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations. Scientific reports
- Poster: Peluso, Paul et al. (2019) Single molecule High-Fidelity (HiFi) Sequencing with >10 kb libraries
- Poster: Rowell, W. et al. (2018) Comprehensive variant detection in a human genome with PacBio high-fidelity reads
- Poster: Larrea, Andres et al. (2018) A simple segue from Sanger to high-throughput SMRT Sequencing with a M13 barcoding system
- Poster: Kingan, Sarah et al. (2018) FALCON-Phase integrates PacBio and HiC data for de novo assembly, scaffolding and phasing of a diploid Puerto Rican genome (HG00733)
- Poster: Audano, Peter A. et al. (2018) Improving the reference with a diversity panel of sequence-resolved structural variation
- Poster: Wenger, Aaron et al. (2018) Joint calling and PacBio SMRT Sequencing for indel and structural variant detection in populations
- Poster: McLaughlin, Ian et al. (2018) No-amp targeted SMRT sequencing using a CRISPR-Cas9 enrichment method
- Poster: Ekholm, J. et al. (2018) Amplification-free, CRISPR-Cas9 targeted enrichment and SMRT Sequencing of repeat-expansion disease causative genomic regions
- Poster: Ranade, S. et al. (2018) High-throughput SMRT Sequencing of clinically relevant targets
- Poster: Vogelsang, R. et al. (2018) Population-scale discovery of structural variants with PacBio SMRT Sequencing
- Poster: Liqing, Tian et al. (2018) Allelic specificity of immunoglobulin heavy chain (IGH@) translocation in B-cell acute lymphoblastic leukemia (B-ALL) unveiled by long-read sequencing
- Poster: Ashby, M. et al. (2018) Scalability and reliability improvements to the Iso-Seq analysis pipeline enables higher throughput sequencing of full-length cancer transcripts
- Poster: Ho, Yeung et al. (2018) The role of androgen receptor variant AR-V9 in prostate cancer
- Poster: Clark, Tyson A. et al. (2018) Amplification-free targeted enrichment and SMRT Sequencing of repeat-expansion genomic regions
- Poster: Chakraborty, Shreyasee et al. (2018) Mitochondrial DNA sequencing using PacBio SMRT technology
- Poster: Wenger, A., et al. (2017) Detecting pathogenic structural variants with long-read PacBio SMRT Sequencing
- Poster: McLaughlin, I., et al. (2017) Targeted sequencing using a long-read sequencing technology
- Poster: Clark, Tyson A. et al. (2017) Targeted enrichment without amplification and SMRT Sequencing of repeat-expansion disease causative genomic regions
- Poster: Kingan, S. et al. (2017) Structural variant detection with low-coverage PacBio sequencing
- Poster: Hickey, L. et al. (2017) Detecting pathogenic structural variants with low-coverage PacBio sequencing.
- Poster: Ekholm, J. et al. (2017) Screening for causative structural variants in neurological disorders using long-read sequencing
- Poster: Baybayan, P. et al. (2017) Detection of low-frequency somatic variants using Single-Molecule, Real-Time Sequencing
- Poster: Ashby, M. et al. (2017) Simplified sequencing of full-length isoforms in cancer on the PacBio Sequel platform
- Poster: Clark, Tyson A. et al. (2017) SMRT Sequencing of full-length androgen receptor isoforms in prostate cancer reveals previously hidden drug resistant variants
- Poster: Kujawa, Steve et al. (2017) A method for the identification of variants in Alzheimer’s disease candidate genes and transcripts using hybridization capture combined with long-read sequencing
- Poster: Ekholm, Jenny et al. (2017) Screening and characterization of causative structural variants for bipolar disorder in a significantly linked chromosomal region onXq24-q27 in an extended pedigree from a genetic isolate
- Poster: Wenger, Aaron et al. (2017) Structural variant detection with low-coverage Pacbio sequencing
- Poster: Oh, Steve et al. (2017) T-cell receptor profiling using PacBio sequencing of SMARTer libraries
- Poster: Clark, T. A. et al. (2017) Targeted SMRT Sequencing of difficult regions of the genome using a Cas9, non-amplification based method
- Poster: Ashby, Meredith et al. (2017) Using the PacBio IsoSeq method to search for novel colorectal cancer biomarkers
- Poster: Hall, Richard et al. (2017) Using the PacBio Sequel System to taxonomically and functionally classify metagenomic samples in a trial of patients undergoing fecal microbiota transplantation
- Poster: Eng, K. et al. (2016) Target enrichment using a neurology panel for 12 barcoded genomic DNA samples on the PacBio SMRT Sequencing platform
- Poster: McCalmon, S. et al. (2016) “SMRTer Confirmation”: Scalable clinical read-through variant confirmation using the Pacific Biosciences SMRT Sequencing platform
- Poster: Tassone, F. et al. (2016) Alternative splicing in FMR1 premutations carriers
- Poster: Watson, C. T. et al. (2016) Characterizing haplotype diversity at the immunoglobulin heavy chain locus across human populations using novel long-read sequencing and assembly approaches
- Aro, Lori and Heiner, Cheryl (2019) Webinar: Amplicon sequencing with confidence – High-fidelity, long-read PacBio sequencing solutions
- Korlach, Jonas and Corney, Dave (2018) Webinar: A new paradigm in DNA sequencing – Highly accurate single-molecule long reads
- (2018) Tutorial: Iso-Seq analysis application [SMRT Link v6.0.0]
- (2018) Tutorial: Structural variant calling [SMRT Link v6.0.0]
- Scott, Stuart (2018) ASHG PacBio Workshop: Amplicon SMRT Sequencing applications in human genetics
- Song, Janet (2018) ASHG PacBio Workshop: Characterization of a large, human-specific tandem repeat array associated with bipolar disorder and schizophrenia
- Korlach, Jonas (2018) ASHG PacBio Workshop: PacBio product updates and roadmap – announcing the release of new chemistry and software
- Tseng, Elizabeth (2018) ASHG PacBio Workshop: The Iso-Seq method for discovering alternative splicing in human diseases
- Korlach, Jonas and Lleras, Roberto (2018) User Group Meeting: Structural variant calling in SMRT Link 6.0
- Graves-Lindsay, Tina (2018) User Group Meeting: The trials and tribulations of high quality human genome assembly
- Pillai, Nisha (2018) Webinar: Assessing the targeted regions using a PacBio Amplicon analysis applications
- Pillai, Nisha (2018) Webinar: Survey of transcriptome diversity using Iso-Seq analysis
- Pillai, Nisha (2018) Webinar: A sketch of assembly recipes for PacBio data
- Ameur, A. and Graves-Lindsay, T. and Peluso, P. (2018) Webinar: Assembling high-quality human reference genomes for global populations
- Korlach, Jonas (2018) Podcast: Why the diversity of genomic data matters
- Sedlazeck, Fritz (2018) Webinar: Size Matters: Accurate detection and phasing of structural variations
- Hoischen, A. and Wenger, A (2018) Webinar: Sequencing structural variants for disease gene discovery and population genetics
- Wenger, Aaron (2017) Video: Structural variant detection with SMRT Sequencing
- Jacob, Howard (2017) Podcast: Huh? 30 million Americans have a rare disease? Howard Jacob on the state of clinical sequencing
- Brunner, Han (2017) ASHG PacBio Workshop: Long-read sequencing for detecting clinically relevant structural variation
- Lee, Charles (2017) ASHG PacBio Workshop: Multiplatform discovery of haplotype-resolved structural variation in human genome
- Korlach, Jonas (2017) ASHG PacBio Workshop: PacBio applications updates & future roadmap
- (2017) Video: Discover structural variation with long-read sequencing
- Wenger, Aaron (2017) Webinar: Detecting structural variants in PacBio reads – tools and applications
- Shendure, Jay (2017) Podcast: Exploring the exome and the future of genomics with Jay Shendure
- (2017) Tutorial: Minor variant analysis [SMRT Link v5.0.0]
- Ranade, Swati (2017) Webinar: A paradigm shift in HLA sequencing: from exons to high-resolution allele-level HLA yyping
- Wenger, Aaron (2017) Webinar: Structural variant detection in SMRT Link 5 with PBSV
- Kingan, Sarah (2017) Webinar: Understanding, curating, and analyzing your diploid genome assembly
- Korlach, Jonas (2017) Webinar: Addressing “NGS Dead Zones” with third generation PacBio sequencing
- Kujawa, Steve (2017) Webinar: PacBio targeted sequencing of long amplicons using PCR or hybrid capture
- Ashby, Meredith (2017) Webinar: Chasing alternative splicing in cancer: Simplified full-length isoform sequencing
- Turner, Stephen (2017) Webinar: An introduction to PacBio’s long-read sequencing & how it has been used to make important scientific discoveries
- Roy, Margaret (2017) AGBT PacBio Workshop: De novo sequencing of the naked mole rat genome
- Schatz, Michael (2017) AGBT Conference: Personalized phased diploid genomes of the EN-TEx samples
- PacBio Certified Service Providers (2018)
- Application Brief: Large genome whole genome sequencing – Best Practices (2018)
- Application Brief: Targeted Sequencing of Amplicons – Best Practices (2018)
- Application Brief: Long-read RNA sequencing – Best Practices (2018)
- SMRT Sequencing Brochure: Revolutionize genomics with SMRT Sequencing (2018)
- Application Brief: Low-coverage, long-read whole genome sequencing for structural variation – Best Practices (2018)
- Infographic: Identify the cause of unsolved genetic disease with long-read sequencing (2018)
- Application Brochure: No-Amp targeted sequencing. (2018)
- Whitepaper: Structural variation in the human genome (2017)
- Infographic: Structural variants and disease (2017)
- Case Study: SMRT sequencing brings clarity to HIV vaccine and transplant research at the Wisconsin national primate research center. (2017)
- Cancer Brochure: Discover the hidden landscape of cancer variants (2017)
- Case Study: Improving precision medicine studies in Asia using ethnicity-specific human reference genomes and PacBio long-read sequencing (2017)
- SMRT Analysis Brochure: Gain a deeper understanding of your sequencing data (2017)
- Product Note: Fast, high-resolution DNA sizing with the fragment analyzer system (2016)
- Application Note: Multiplex target enrichment using barcoded multi-kilobase fragments and probe-based capture technologies (2016)
- Epigenetics Application Brochure: Characterize the epigenetic landscape of your genome. (2016)
- Case Study: Scientists deconstruct cancer complexity through genome and transcriptome analysis (2016)