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
- Sedlazeck, Fritz J et al. (2018) Accurate detection of complex structural variations using single-molecule sequencing. Nature Methods
- Bultitude, W P et al. (2018) KIR2DL1 allele sequence extensions and discovery of 2DL1*0010102 and 2DL1*0010103 alleles by DNA sequencing. HLA
- Sedlazeck, Fritz J et al. (2018) Piercing the dark matter: bioinformatics of long-range sequencing and mapping. Nature Reviews. Genetics
- 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
- Han, Seung Yub et al. (2018) Coupling of single molecule, long read sequencing with IMGT/HighV-QUEST analysis expedites identification of SIV gp140-specific antibodies from scFv phage display libraries. Frontiers in Immunology
- Aneichyk, Tatsiana et al. (2018) Dissecting the causal mechanism of X-linked Dystonia-Parkinsonism by integrating genome and transcriptome assembly. Cell
- Weerts, M J A et al. (2018) Sensitive detection of mitochondrial DNA variants for analysis of mitochondrial DNA-enriched extracts from frozen tumor tissue. Scientific Reports
- Atack, John M et al. (2018) Phasevarions of bacterial pathogens: Methylomics sheds new light on old enemies. Trends in Microbiology
- Ardui, Simon et al. (2018) Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics. Nucleic Acids Research
- Turner, T R et al. (2018) Single molecule real-time (SMRT®) DNA sequencing of HLA genes at ultra-high resolution from 126 International HLA and Immunogenetics Workshop cell lines. HLA
- Reiner, Jennifer et al. (2018) Cytogenomic identification and long-read single molecule real-time (SMRT) sequencing of a Bardet-Biedl Syndrome 9 (BBS9) deletion. NPJ Genomic Medicine
- Paulk, Nicole K et al. (2017) Bioengineered AAV capsids with combined high human liver transduction in vivo and unique humoral seroreactivity. Molecular Therapy
- Asur, Rajalakshmi S et al. (2018) Somatic mosaicism of an intragenic FANCB duplication in both fibroblast and peripheral blood cells observed in a Fanconi anemia patient leads to milder phenotype. Molecular Genetics & Genomic Medicine
- Hemadou, Audrey et al. (2017) Pacific Biosciences sequencing and IMGT/HighV-QUEST analysis of full-length single chain fragment variable from an in vivo selected phage-display combinatorial Library. Frontiers in Immunology
- Hickey, Luke et al. (2017) Hunting structural variants: Population by population Front Line Genomics Magazine
- Lagarde, Julien et al. (2017) High-throughput annotation of full-length long noncoding RNAs with capture long-read sequencing. Nature Genetics
- Balázs, Zsolt et al. (2017) Long-read sequencing of human cytomegalovirus transcriptome reveals RNA isoforms carrying distinct coding potentials. Scientific Reports
- Lodé, Laurence et al. (2018) Single-molecule DNA sequencing of acute myeloid leukemia and myelodysplastic syndromes with multiple TP53 alterations. Haematologica
- Hickey, L. et al. (2017) Structural variation offers new home for disease associations and gene discovery Drug Discovery and Development Magazine
- Young, George R et al. (2017) HIV-1 infection of primary CD4(+) T cells regulates the expression of specific HERV-K (HML-2) elements. Journal of Virology
- Tsai, Yu-Chih et al. (2017) Amplification-free, CRISPR-Cas9 targeted enrichment and SMRT Sequencing of repeat-expansion disease causative genomic regions BioRxiv
- Gonçalves, Ana et al. (2017) Exonization of an intronic LINE-1 element causing Becker muscular dystrophy as a novel mutational mechanism in dystrophin gene. Genes
- Wilbe, Maria et al. (2017) A novel approach using long-read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders. Prenatal Diagnosis
- Chaisson, Mark J.P. et al. (2017) Multi-platform discovery of haplotype-resolved structural variation in human genomes BioRxiv
- Tseng, Elizabeth et al. (2017) Altered expression of the FMR1 splicing variants landscape in premutation carriers. Biochimica et Biophysica Acta
- Schüle, Birgitt et al. (2017) Parkinsons disease associated with pure ATXN10 repeat NPJ Parkinson's Disease
- Pei, Weike et al. (2017) Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature
- Xiao, Chuan-Le et al. (2017) N6-methyladenine DNA modification in human genome BioRxiv
- Forde, Brian M. et al. (2017) SMRT Sequencing reveals differential patterns of methylation in two O111:H- Shiga toxigenic Escherichia coli isolates from a historic hemolytic uremic syndrome outbreak in Australia BioRxiv
- Nattestad, Maria et al. (2017) Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line BioRxiv
- Chen, Shi-Yi et al. (2017) A transcriptome atlas of rabbit revealed by PacBio single-molecule long-read sequencing. Scientific Reports
- Gao, Shan et al. (2017) Two novel lncRNAs discovered in human mitochondrial DNA using PacBio full-length transcriptome data. Mitochondrion
- Albrecht, V et al. (2017) Dual redundant sequencing strategy: Full-length gene characterisation of 1056 novel and confirmatory HLA alleles. HLA
- Zhao, J et al. (2017) Reduction in fecal microbiota diversity and short-chain fatty acid producers in Methicillin-resistant Staphylococcus aureus infected individuals as revealed by PacBio single molecule, real-time sequencing technology. European Journal of Clinical Microbiology & Infectious Diseases
- Komor, Malgorzata A et al. (2017) Identification of differentially expressed splice variants by the proteogenomic pipeline Splicify. Molecular & Cellular Proteomics
- Poster: Ranade, S. et al. (2018) High-throughput SMRT Sequencing of clinically televant 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
- Poster: Wenger, A. et al. (2016) Effect of coverage depth and haplotype phasing on structural variant detection with PacBio long reads
- Poster: Carroll, A. et al. (2016) Structural variant combining Illumina and low-coverage PacBio
- Poster: Pollard, M. O. et al. (2016) The MHC Diversity in Africa Project (MDAP) pilot – 125 African high resolution HLA types from 5 populations
- Poster: Kujawa, S. et al. (2016) A method for the identification of variants in Alzheimer’s disease candidate genes and transcripts using hybridization capture combined with long-read sequencing
- Poster: Sethuraman, A. et al. (2016) Characterization of the Poly-T variants in the TOMM40 gene using PacBio long reads
- Poster: Ekholm, J. et al. (2016) Enrichment of unamplified DNA and long-read SMRT Sequencing to unlock repeat expansion disorders
- Poster: Cereb, N et al. (2016) Whole gene sequencing of KIR-3DL1 with SMRT Sequencing and the distribution of allelic variants in different ethnic groups
- Poster: Jenny Gu, Kevin Eng, Anand Sethuraman, Steve Kujawa et al. (2016) Multiplex target enrichment using barcoded multi-kilobase fragments and probe-based capture technologies
- Pillai, Nisha (2018) Webinar: A sketch of assembly recipies 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
- 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]
- (2017) Tutorial: Structural variant calling [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
- Korlach, Jonas (2017) AGBT PacBio Workshop: SMRT Sequencing roadmap: better throughput, lower costs
- Schatz, Michael (2017) AGBT Conference: Personalized phased diploid genomes of the EN-TEx samples
- Ameur, Adam (2017) AGBT Virtual Poster: Analysis method for amplification-free SMRT sequencing and assessment on repeat expansions in Huntington’s disease
- Auvignen, Petra (2017) AGBT Virtual Poster: Interspecies interation amoung meat spoilage-related lactic acid bacteria
- Ashby, Meredith (2017) AGBT Virtual Poster: Using the PacBio Iso-Seq method to search for novel colorectal cancer biomarkers
- Clark, T. A. and Tsai, Y. and Greenberg, D. (2017) Targeted SMRT Sequencing of difficult regions of the genome using a Cas9, non-amplification based method
- Glyllensten, Ulf (2017) AGBT Virtual Poster: Generation of local reference genomes using PacBio and BioNano data, and analysis of the “dark matter” of structural variants in 1000 Swedish genomes
- Paulin, Lars (2017) AGBT Virtual Poster: Single-molecule sequencing reveals the presence of distinct JC polyomavirus populations in patients with progressive multifocal leukoencephalopathy
- (2017) Tutorial: HGAP4 de novo assembly application [SMRT Link v5.0.0]
- (2017) Tutorial: Iso-Seq analysis application [SMRT Link v5.0.0]
- (2017) Tutorial: Long amplicon analysis application [SMRT Link v5.0.0]
- Tishkoff, Sarah (2016) Podcast: African genomics a moral obligation, says Sarah Tishkoff, U Penn
- Korlach, Jonas (2016) ASHG PacBio Workshop: A future of high-quality genomes, transcriptomes, and epigenomes
- Application Brief: Long-read RNA sequencing – Best Practices. (2018)
- Application Brief: Low-coverage, long-read whole genome sequencing for structural variation – Best Practices. (2018)
- Application Brief: Large genome whole genome sequencing – Best Practices. (2018)
- Application Brochure: No-Amp targeted sequencing. (2018)
- SMRT Sequencing Brochure: Revolutionize genomics with SMRT Sequencing. (2018)
- PacBio Certified Service Providers (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)
- Human Biomedical Research Brochure: The most comprehensive view of the human genome (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)
- Application Note: Targeted sequencing and chromosomal haplotype assembly using Cergentis TLA technology with SMRT Sequencing. (2016)
- Epigenetics Application Brochure: Characterize the epigenetic landscape of your genome. (2016)
- Case Study: Scientists deconstruct cancer complexity through genome and transcriptome analysis. (2016)