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Tuesday, September 7, 2021

Long-Read Genome Sequencing for the Molecular Understanding of Neurodevelopmental Disorders   

In this ESHG 2021 Workshop, PacBio Chief Scientific Officer Jonas Korlach, Ph.D., describes why HiFi sequencing improves the ability to detect pathogenic variants that previously went undetected with other technologies. He then turns the microphone over to Susan Hiatt, Ph.D. from HudsonAlpha Institute for Biotechnology. Dr. Hiatt discusses how she and her team used HiFi sequencing in their rare disease research to discover genomic variation missed by whole-exome or genome sequencing studies using short reads, allowing her team to uncover medical mysteries that had previously gone unexplained. 

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Monday, September 6, 2021

Revealing Mechanisms of Bacterial Virulence and Adaptation with PacBio SMRT Sequencing

In this talk, speakers will describe the importance of high accuracy and long read length for generating closed bacterial assemblies. Speakers will also share examples of how hard-to-assemble domains and plasmids impact important biological traits including, pathogen virulence and anti-microbial resistance. Finally, they will provide an overview of the advantages of highly accurate long-read sequencing for outbreak tracking.

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Monday, August 23, 2021

Identifying Key Players in Host-Microbiome Interactions with High Resolution 16S Sequencing

In this talk, speakers provide an understanding of how highly accurate long-read sequencing of extended 16S amplicons enables the identification of metagenome community members at higher taxonomic resolution than short-read methods. You’ll also hear examples of how metagenome functions that impact human health can be driven by specific species or strains within a community and learn how the gut microbiome can impact drug efficacy.

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Wednesday, August 11, 2021

Resolving Viral Evolution and Quasispecies Diversity with HiFi Sequencing

In this talk, speakers provide an understanding HiFi sequencing methods for resolving viral diversity in complex systems, examples of how HiFi sequencing can phase entire viral genes or genomes, revealing quasispecies diversity within patients, and how combining fully-phased minor variant data with other data types provides insights into viral evolution, immune escape, and drug resistance.

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Tuesday, July 27, 2021

Optimizing for Information: What Richer Data and Better Assemblies Reveal About Metagenome Structure and Function

In this talk, speakers provide an overview of PacBio-recommended tools for metagenome sequencing analysis, where to download example test data, the typical performance for HiFi metagenome sequencing of fecal samples, the impact of read accuracy on metagenome assembly of long-read data, and finally, how deep sequencing that combines HiFi reads and Hi-C data can enormously increase recovery of high-quality MAGs and connect plasmids and viruses to host strains.

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Tuesday, June 15, 2021

Long-read Sequencing and Optical Mapping of ATXN10 Repeat Expansion

Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal-dominant disorder caused by an expanded intronic pentanucleotide repeat in the ATXN10 gene. This repeat expansion when fully penetrant can be typically expected between 850 and 4500 repeats or 4.25 to 22.5 kb. Current diagnostic assays using PCR-based methods or Southern blotting cannot accurately size or resolve the genomic structure of the ATXN10 repeat. In this talk, Dr. Birgitt Schuele elaborates that CRISPR-Cas9 enrichment/single molecule real time (SMRT) sequencing technology and optical mapping now allow for accurate sizing of the repeat expansion, repeat composition, and can resolve somatic mosaicism, which are critical…

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Tuesday, June 15, 2021

Altered Alternative Splicing Process in FMR1 Premutation Carriers

In this talk, Dr. Flora Tassone focuses on the identification of alternative splicing isoforms at the FMR1 locus (both sense and antisense direction) in individual carriers of the FMR1 premutation allele, using the SMRT Sequencing approach. The characterization of a transcriptional profile could help to define a biomarker for monitoring disease progression and development.

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Tuesday, June 15, 2021

Uncovering Neurological Disorders Through an Examination of VNTRs

Many neurological diseases result from expansion of unstable variable nucleotide tandem repeats (VNTRs) that influence gene transcription of neighboring genes. In this talk, Dr. Henne Holstege presents research that investigated VNTRs across several genomes including a 115-year-old cognitively healthy individual. She and her group found that the genes that contained most VNTRs, of which PTPRN2 and DLGAP2 are the most prominent examples, were found to be predominantly expressed in the brain and associated with a wide variety of neurological disorders.

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Tuesday, June 15, 2021

Long-read Sequencing to Assess an Expanded Repeat in C9orf72

In this presentation, Dr. Marka van Blitterswijk shares the exciting results of her most recent targeted long-read sequencing study. Together with her colleagues, she performed No-Amp sequencing to examine an expanded GGGGCC-repeat in C9orf72, which causes fatal neurodegenerative diseases. Her team assessed the length of the C9orf72 expansion, as well as the presence of interruptions, thus revealing relevant clinico-pathological associations and demonstrating how powerful No-Amp sequencing is.

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Tuesday, June 15, 2021

The Evolution and Function of a Large Tandem Repeat Associated with ALS

In this talk, Dr. Meredith Course presents her research on uncovering a 69-bp human-specific tandem repeat expansion in the final intron of WDR7. Larger repeat copy number is significantly associated with sporadic ALS cases, suggesting that it plays a role in disease susceptibility. Long-read sequencing reveals remarkable internal nucleotide variation, which was harnessed to determine the evolutionary origin of the expansion, its mechanism of replication, and its current state in modern-day humans. Each copy of the repeat has been determined to be able to form microRNAs and aggregate in cells and may sequester ALS-related RNA-binding proteins.

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Tuesday, June 15, 2021

Improving the Prognosis and Genetic Counseling in DM1 Patients

In this talk, Dr. Stephanie Tome describes using PacBio Single Molecule, Real-Time (SMRT) Sequencing to precisely measure large CTG repeat size and identify sequence interruptions of expanded allele to understand clinical and genetic variability in DM1 patients, sequencing several DM1 patients with CTG repeat expansion ranging from 130 to > 1000 CTG repeats on the Sequel I and II Systems from amplicons. She obtained more than 77% full DM1 reads per sample, with >70% of the reads from expanded alleles. The data includes long reads in the expected size range for all samples, including DM1 patients with more than 1000…

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Tuesday, June 15, 2021

Multiplex, Long-Read Sequencing of Ataxia Repeat Expansions

In this talk, Dr. Zachary McEachin describes how No-Amp targeted sequencing enables sequencing analysis of multiple (at least 15) Ataxia-related repeat expansion loci in one assay, presenting example sequencing results with selected samples from Ataxia patients and patients with unknown diagnostics. He demonstrates how PacBio HiFi sequencing with the No-Amp approach could provide repeat expansion and sequence interruption information at the target loci that is not available with PCR or southern-blot based diagnostics assays.

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