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Tuesday, November 2, 2021

Scalable RNA Isoform Sequencing using Intramolecular Multiplexed cDNAs

While RNA-sequencing has dramatically accelerated our understanding of biology, quantitation and discovery of full-length RNA isoforms resulting from alternative splicing remain poorly resolved. Alternative splicing is a core regulatory process that modulates the structure, expression, and localization of expressed proteins through differential exon and/or UTR splicing during transcript maturation. Beyond being an integral component of cellular development and homeostatic maintenance, RNA splicing is implicated in a wide range of pathologies with hallmark isoforms being linked to cardiovascular, neurological, and immunological diseases. Current limitations in isoform quantitation and discovery arise from the inability of existing sequencing platforms to scalably sequence full-length…

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Tuesday, November 2, 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, November 2, 2021

HiFi Sequencing: See What You’ve Been Missing

PacBio Vice President of Segment Marketing, Dr. Jennifer Stone, demonstrates how HiFi sequencing is changing the game in human genetics by sharing some of the exciting milestones and seminal publications our technology has produced this year.

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Tuesday, November 2, 2021

Integrated Rare Disease using Long-Read Genome Sequencing

Genomic variation beyond single nucleotide variants, including structural variation (SV), copy number variants (CNV), and repeat expansions, plays a significant role in rare disease. However, current technologies require multiple tests to fully access these variants, resulting in complex testing algorithms and the potential for missed diagnoses. Long-read genome sequencing offers the ability to accurately detect SNV, CNV, SV, and expansions with a single test. This presentation will highlight the integrated analyses offered by HiFi sequencing, using case examples demonstrating the potential for a unified test.

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Friday, October 29, 2021

Targeting Clinically Significant Dark Regions of the Human Genome with High-Accuracy, Long-Read Sequencing

There are many clinically important genes in “dark” regions of the human genome. These regions are characterized as dark due to a paucity of NGS coverage as a result of short-read sequencing or mapping difficulties. Low NGS sequencing yield can arise in these regions due to the presence of various repeat elements or biased base composition while inaccurate mapping can result from segmental duplications. Long-read sequencing coupled with an optimized, robust enrichment method has the potential to illuminate these dark regions. 

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Friday, October 29, 2021

Resolving Complex Pathogenic Alleles using HiFi Long-Range Amplicon Data and a New Clustering Algorithm

Many genetic diseases are mapped to structurally complex loci. These regions contain highly similar paralogous alleles (>99% identity) that span kilobases within the human genome. Comprehensive screening for pathogenic variants is incomplete and labor intensive using short-reads or optical mapping. In contrast, long-range amplification and PacBio HiFi sequencing fully and directly resolve and phase a wide range of pathogenic variants without inference. To capitalize on the accuracy of HiFi data we designed a new amplicon analysis tool, pbAA. pbAA can rapidly deconvolve a mixture of haplotypes, enabling precise diplotyping, and disease allele classification. 

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Thursday, October 28, 2021

HiFiViral: A Novel Method for Surveillance of SARS-CoV-2 that is Robust Across Sample Input Quantities and the Evolution of New Variants

The COVID-19 pandemic continues to be a major global epidemiological challenge with the ongoing emergence of new strain lineages that are more contagious, more virulent, drug-resistant, and in some cases evade vaccine-induced immunity. In response, the HiFiViral SARS-CoV-2 kit was developed as a scalable solution for the Sequel II and Sequel IIe Systems. Unlike amplicon sequencing, the HiFiViral SARS-CoV-2 kit uses tiled probes, resulting in robust genome coverage across varying viral input quantities despite the presence of new variants. The use of highly accurate long reads, or HiFi reads, enables comprehensive variant detection, including single nucleotide variants, indels, and structural…

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PacBio Grants Equity Incentive Award to New Employee

Friday, November 19, 2021

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