In this SMRT Science Journal Club talk, Anoushka Joglekar from Weill Cornell Medicine discusses how she and her colleagues are developing tools to produce an isoform view of the brain in order to better understand developmental disorders and neurodegenerative disease.
In this SMRT Science Journal Club talk, Phillip Tai from the University of Massachusetts Medical School discusses his investigation in the design compatibility of CRISPR components in AAV vectors.
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.
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.
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.
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…
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.
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…
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.
Through Pharmacogenomics (PGx), we can explore how a person’s genome affects their response to drugs to enable the development of safe and effective medications tailored to their genetic makeup. In this talk, you’ll learn how PacBio HiFi sequencing: is cost-effective and highly accurate; enables comprehensive interrogation of pharmacogenomics genes—detecting all types of variants even in challenging regions; allows for the sequencing of pharmacogenomics genes as single-gene assays or large panels; produces data that is highly concordant with other technologies—adding value through comprehensive variant detection, copy number assessment, and phasing.
Join PacBio’s Mike Weiand to hear how gene editing protocols can benefit from long-read sequencing at multiple stages to optimize and enhance vector integrity. This method allows researchers to reveal findings that other sequencing methods can not identify due to read-length limitations or amplification biases.
The Sequel IIe System produces highly accurate long reads (HiFi reads) quickly and cost-effectively thanks to increased computational capacity and on-instrument data processing. This results in a significant reduction of overall secondary analysis time and reduces the computational needs in terms of file transfer and data storage. This webinar provides an overview of PacBio data for beginner and advanced users of HiFi reads, exploring the content of PacBio BAM files, providing examples of how HiFi reads can be filtered, and going through recommendations for downstream analysis.
With highly accurate long reads (HiFi reads) of >99% accuracy, the Sequel IIe System is the tool of choice for producing reference quality assemblies, calling variants with the highest precision, reading full-length transcripts, characterizing isoform diversity, and many more applications. To maximize the quality of your results, DNA and sample preparation are critical steps in your sequencing workflow. In this webinar we cover the following points: preparing DNA for PacBio HiFi sequencing, selecting the right HiFi library preparation protocol for your project, and interpreting sequencing metrics and troubleshooting.
In this CSHL Biology of Genomes 2021 virtual workshop, Jonas Korlach from PacBio discusses examples of how advances in highly accurate long-read (HiFi) sequencing have enabled new developments in SARS-CoV-2 surveillance.
In this CSHL Biology of Genomes 2021 virtual workshop, Aaron Wenger from PacBio discusses examples of how advances in highly accurate long-read (HiFi) sequencing have enabled exciting developments in human genome research, including sequencing the genomes of 100 individuals with unexplained diseases.