In-situ multiomics is revolutionizing research in oncology, immunology and neurobiology. However, speed and throughput are major bottlenecks for these critical studies. Here, we present data from a novel in-situ sequencing system, with sub-micron resolution and ultra-high throughput capacity, employing rapid 4-color SBS chemistry to profile RNA transcripts and proteins in FFPE tissue. The system also generates virtual H&E images, producing multi-modal spatial images of 40 cm2 of tissue in <24 hours.

Learning Objectives: 

1. Learn about the G4 Sequencing Platform and G4X Spatial Sequencer.

2. Discover how in-situ sequencing can be applied to profile RNA transcripts and proteins in Tissue.

3. Learn about applications and use-cases of in-situ sequencing.

Laboratories use the same laboratory equipment they invested in for COVID testing to perform PGx testing. With COVID testing reimbursement dropping, many laboratorians are considering implementing PGx testing. PGx test panel design and test utilization that align with payers’ medical necessity definitions are key to pharmacogenomics laboratories’ financial viability and sustainability. Payers currently recognize some clinical pharmacogenomic (PGx) testing has sufficient clinical utility evidence to justify their coverage and reimbursement for their patient populations and as such have existing coverage and reimbursement and billing and coding guidelines. For the purposes of this webinar, Dr. Winslow will focus on laboratories’ optimizing PGx test panel design and utilization based on payers’ existing coverage and reimbursement guidelines for pharmacogenetic associations that are related to drug metabolizing enzyme gene variants, drug transporter gene variants, and gene variants that predispose a patient to certain adverse events and drug efficacy.

Learning Objectives:

1. Review educated financial decisions when considering implementing clinical PGx testing in the laboratory.

2. Differentiate between implementing a clinical PGx test for which CPT codes and payers’ policies exist and implementing one for which CPT codes and payer policies do not yet exist in terms of time from test implementation to reimbursement.

3. Describe how to optimize PGx test panel design and utilization using payers’ existing coverage and reimbursement guidelines to positively impact the PGx laboratory’s profits and losses.

Oligonucleotide therapeutics have emerged as a promising novel class of drugs to treat a wide range of diseases. The development of these therapeutics relies on the proper use of chemical building blocks called phosphoramidites to generate high‑quality oligonucleotides. This webinar discusses techniques for phosphoramidite synthesis, selection, and evaluation for the development of oligonucleotide drugs.

Learning Objectives: 

1. Identify phosphoramidites for oligonucleotide therapeutic development and manufacturing.

2. Review phosphoramidite impurities and their potential impacts on oligonucleotide therapeutics.

Join us as we delve into the forefront of SARS-CoV-2 diagnostics and GenScript's transformative impact in the fight against COVID-19. We'll discuss the emergence of COVID-19 and GenScript's rapid response with the development of their cPass SARS-CoV-2 nAb Detection Kit and SARS-CoV-2 qPCR kit. Gain insights into the diagnostic development workflow and learn about GenScript's cutting-edge solutions for target identification, assay development, optimization, and production that made assay development possible. We will also share case studies showcasing how customers have leveraged GenScript for IVD development including a highlight of our recent research grant awardees and their diagnostic projects.

In this talk, you will: 

1. Learn about GenScript's development of two COVID-19 related diagnostics.

2. Learn about GenScript's IVD development solutions at each stage of development.

3. Hear about other research in action with GenScript support.

Women experience a variety of unique sexual health issues that are often under appreciated by the general public and even by healthcare providers. Compared to other populations, cisgender women are disproportionately impacted by sexually transmitted infections. Due to their anatomy and potential for pregnancy, the impacts of such infections can also have devastating impacts, especially if they go undiagnosed and untreated. Vaginal infections such as bacterial vaginosis and trichomoniasis can not only lead to unpleasant symptoms such as vaginal discharge, odor, and irritation, but also have been associated with increased risk of HIV acquisition and adverse birth outcomes. Vulvovaginal candidiasis, which not linked to these specific outcomes, is extremely common and can negatively impact the quality of life of the women who experience it.

Research plays a crucial role in advancing our understanding of vaginal health. By conducting thorough research and utilizing specialized tests, scientists can investigate various aspects of vaginal health, such as the presence of specific pathogens, imbalances in the vaginal microbiota, or the effectiveness of certain treatments. This research helps in developing evidence-based guidelines, improving diagnostic accuracy, and ultimately enhancing the overall management and care of vaginal health conditions.

In this talk, we will discuss the epidemiology and clinical features of the three most common vaginal infections faced by women. Two of these are thought to be sexually transmitted or sexually associated (BV and trichomoniasis). These three clinical entities overlap in many ways in their presenting signs, symptoms and diagnostic findings, so we will discuss an approach to ascertaining the correct clinical diagnosis using a combination of physical exam, point of care testing, and laboratory diagnostics that are currently on the market.

Learning Objectives:

1. Distinguish between the clinical features of common causes of infectious vaginitis (e.g., bacterial vaginosis, trichomoniasis, vulvovaginal candidiasis).

2. Evaluate a patient presenting with vaginal symptoms through physical exam, point-of-care tests and laboratory assessments.

3. Review the molecular diagnostics that are currently available for the evaluation of vaginal symptoms.

Nucleic acid agarose gel electrophoresis is a fundamental technique in molecular biology, boasting a rich history of advancements and innovations spanning over half a century. This technique plays a crucial role in various workflows, including basic analysis, sequencing library preparation, and fragment purification. Nevertheless, the wide range of applications for nucleic acid separation brings with it the risk of errors, mistakes, and mishaps that have the potential to diminish the quality of the ultimate outcomes. Join our seminar as we delve into the most common causes of poor outcomes and unveil innovative solutions to enhance your electrophoresis workflow.

Join this year's poster presenters in the Poster Hall during the Poster Discussion, Wednesday, May 15th, from 10:00 –11:00 AM PDT, to chat live about their posters and latest research and findings.

The last 20 years have seen an explosion of genetic information and data. New technological advances have made it faster and less expensive to understand the human genomes but most of those resources have focused on northern European communities.

Throughout his keynote speech, Dr. Bustamante elaborates on the major challenge to enabling precision health at a global scale, and the bias between those who enroll in state sponsored genomic research and those suffering from chronic disease. More than 30 million people have been genotyped by direct-to-consumer (DTC) companies and/or sequenced by large biobank efforts, providing a potential mechanism for democratizing access to medical interventions and thus catalyzing improvements in patient outcomes as the cost of data acquisition drops. In this keynote speech, Dr. Bustamante presents a novel geno-pheno platform that integrates heterogeneous data sources and applies learnings to common chronic disease conditions.

He further covers how the SARS-CoV-2 pandemic has differentially impacted populations of varied race, ethnicity and socioeconomic status. His research team leveraged a pandemic tracking strategy in which they sequenced viral and host genomes, and transcriptomes from nasopharyngeal swab residuals and integrated them with digital phenotypes from electronic health records. They demonstrated over-representation of individuals possessing Oceanian and Indigenous American ancestry in SARS-CoV-2 positive populations. This work demonstrated the power of multi-omic pandemic tracking and genomic analyses to reveal distinct epidemiologic, genetic and biological associations for those at the highest risk.

The next phase of this work will leverage clinical-grade biobanking, research and clinical genomics, paired with best-in-class ancestry and genome annotation algorithms towards better understanding the genetic architecture of underserved populations and powering the next generation of precision medicine studies. We are particularly interested in understanding post-infectious acute syndromes including those with neuropsychiatric components such as long-covid and associated disorders.

Learning Objectives:

1. Discuss the need for diversity in advancing the future of precision medicine.

2. Uncover the adverse effects caused by the deficiencies in the approach to drug production today.

3. Explore unique mechanisms for enhancing currently employed biobanking practices.

Comprehending the mechanism behind human diseases with an established heritable component represents the forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or the so-called ‘dark regions’ of the human genome. The advent of PacBio as a long-read platform has provided new insights, yet HiFi whole-genome sequencing (WGS) cost remains frequently prohibitive. We introduce a targeted sequencing and analysis framework, Twist Alliance Dark Genes Panel (TADGP), designed to offer phased variants across 389 medically important yet complex autosomal genes. We highlight TADGP accuracy across eleven control samples and compare it to WGS. This demonstrates that TADGP achieves variant calling accuracy comparable to HiFi-WGS data, but at a fraction of the cost. Thus, enabling scalability and broad applicability for studying rare diseases or complementing previously sequenced samples to gain insights into these complex genes.

TADGP revealed several candidate variants across all cases and provided insight into LPA diversity when tested on samples from rare disease and cardiovascular disease cohorts. In both cohorts, we identified novel variants affecting individual disease-associated genes (e.g., IKZF1, KCNE1). Nevertheless, the annotation of the variants across these 389 medically important genes remains challenging due to their underrepresentation in ClinVar and gnomAD. Consequently, we also offer an annotation resource to enhance the evaluation and prioritization of these variants.

Overall, we can demonstrate that TADGP offers a cost-efficient and scalable approach to routinely assess the dark regions of the human genome with clinical relevance.

Learning Objectives:

1. Review the intricacies of medical complex genes, including the factors that contribute to their complexity.

2. Evaluate the advantages and limitations of sequencing methods and technologies in studying these genes.

3. Summarize the latest methods and algorithms utilized to tackle the challenges of analyzing complex genes, focusing on state-of-the-art approaches in the field.

Norovirus is a highly contagious virus and stands as the primary cause of acute gastroenteritis leading to vomiting and diarrhea across all age groups in the United States. Outbreaks of norovirus are especially common during the winter months and, in certain instances, can result in severe illness. This webinar provides an in-depth exploration of the latest insights on norovirus, covering both its clinical and molecular epidemiology. We will examine effective strategies for managing norovirus outbreaks to halt transmission, delve into current treatment options, and discuss candidate vaccines under development. Additionally, the webinar will highlight the importance of diagnostic tests for the swift and precise detection of norovirus infections. We will also identify key challenges that persist in enhancing the control of norovirus-related illnesses.

The Genomes2People Research Program (G2P), led by Robert Green at Brigham and Women’s Hospital, the Broad Institute, Ariadne Labs, and Harvard Medical School, conducts research to accelerate the implementation of genomic medicine and the promise of precision health. In his talk, "History and Future of Tier 1 Genomic Population Screening," Dr. Green discusses the latest advancements in genomics research and the promise it holds for personalized and preventive medicine on a population level, drawing on his work leading the MedSeq Project, BabySeq Project, and Precision Population Health Initiative.

Throughout his talk, Dr. Green highlights the progress made by the MedSeq and BabySeq projects in advancing our understanding of genomics and its application to clinical care. MedSeq explored the use of whole genome sequencing in primary health care and cardiology specialty care, while BabySeq focuses on the use of genomic sequencing as screening in newborns. Dr. Green also co-leads the Precision Population Health (PPH) Initiative which collaborates with health systems to bring the promise of genetic medicine into primary care settings. Most recently, PPH has been piloting screening for the CDC Tier 1 genes for Hereditary Breast/Ovarian Cancer Syndrome, Lynch Syndrome and Familial Hypercholesterolemia in a primary care clinic at the Southcentral Foundation in Alaska.

Dr. Green discusses how the insights gained through these projects are paving the way for implementing a more personalized and preventive approach in medicine. He emphasizes the importance of integrating genomic data into clinical care and the need for policies and guidelines to ensure that this is done in an ethical, responsible and cost effective manner.

Through rigorous scientific research, G2P is establishing a foundation of evidence for genomic medicine that will accelerate the adoption of novel genomics-based technologies and hasten the day when illness is not just treated, but prevented.

Learning Objectives: 

1. Discuss the current state of genomics research and its potential to improve human health through personalized and preventive medicine.

2. Discuss the arguments for and against population based genetic screening.

3. Identify the percentages of healthy adults and infants who carry unanticipated monogenic disease risks or atypical pharmacogenomic variants as observed in the MedSeq and BabySeq projects.

This talk will explore the integration of genomics with electronic health records (EHRs) in biobanks, emphasizing its potential to enhance women's health research. We'll delve into how EHR-linked biobanks can be leveraged to uncover genetic associations with conditions predominantly affecting women, such as endometriosis and discuss strategies for overcoming the challenges in this interdisciplinary field. By bridging these domains, we aim to pave the way for precision medicine approaches tailored specifically to women's health needs.

Learning Objectives: 

1. Discuss the integration of EHR data with genomic research to enhance studies on women's health.

2. Evaluate the application of machine learning clustering techniques to identify endometriosis subtypes and their implications for risk prediction.

3. Examine the potential of machine learning-driven diagnostics to reduce the time to diagnosis and improve early intervention strategies in endometriosis.

Genomics, epigenomics and transcriptomics are often thought of as independent fields, but in our clinical practice we use them combined to increase diagnostic yield both for constitutional and somatic applications.

Genomics relies on short and long read sequencing and karyotyping/optical genome mapping. Epigenomics relies on long read methylation sequencing technology. Transcriptomics currently mainly relies on short read sequencing, but long read sequencing is soon to become more widely used.

Genomic findings, such as small variants, repeat expansions, microsatellite contractions and structural variants/ copy number variants, often need functional assessment to be reportable as likely pathogenic or pathogenic. Epigenomic findings of imprinting defects, preferential allele specific silencing or X chromosome silencing can provide additional indication about the clinical significance of the genomic changes. Transcriptomics further enhances our ability to assign pathogenic significance to variants based on the way they affect transcription levels of the genes affected or their splicing and processing.

As demonstrated through some clinical examples, the best results from this combined usage paradigm are obtained when data analysis is truly integrated and the different datasets are reviewed and analyzed at the same time by the same person.

Combined clinical application of OMICS has in our experience increased the level of certainty of clinical diagnoses and saved clinicians time. Continued consultation with clinical colleagues is important to help them understand when and how to use the OMICS tools available to them.

Learning Objectives: 

1. Review the technical basis of the different OMICS approaches.

2. Discuss the best approaches to use them in combination to solve difficult cases.

3. Summarize some clinical examples that benefitted from their use.

Research and medical genomics require comprehensive and scalable solutions to drive the discovery of novel disease targets, evolutionary drivers, and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size (e.g., SNV/SV) or location (e.g., repeats). Here we present DRAGEN that utilizes novel methods based on multigenomes, hardware acceleration, and machine learning based variant detection to provide novel insights into individual genomes with approximately ~30 minutes computation time (from raw reads to variant detection). DRAGEN outperforms all other state-of-the-art methods in speed and accuracy across all variant types (SNV, indel, STR, SV, CNV) and further incorporates specialized methods to obtain key insights in medically relevant genes (e.g., HLA, SMN, GBA). We showcase DRAGEN across 3,202 genomes and demonstrate its scalability, accuracy, and innovations to further advance the integration of comprehensive genomics for research and medical applications.

Learning Objectives:

1. Explain how genomics analysis can be done comprehensively.

2. Identify the study of all different types of genome variants together.

3. Summarize the utility of DRAGEN software for comprehensive genomics at scale.

The personalized treatment of each cancer patient with targeted therapies selected based on our understanding of the molecular biology of cancer has been the long-standing goal of precision oncology. The Human Project, completed 20 years ago, provided the blueprint for the following cancer genome projects. Today, we can identify the genetic (driver) alteration in 95% of cancer cases based on whole genome sequencing (WGS), Pan-Cancer Analysis of Whole Genomes (PCAWG) Nature 578, 82–93 (2020). According to this study, each cancer harbors an average combination of four to five genetic driver alterations out of thousands of possible mutations of hundreds of cancer driver genes. The early successes of personalizing treatment decisions based on matching one genetic alteration as a predictive biomarker to one targeted therapy are not reproducible in most patients. To solve this problem, we have developed a computational (AI) reasoning method to select N-of-1 treatment options based on the totality of molecular information available for each case instead of providing information about the actionability of genetic alterations one by one.

Learning Objectives: 

1. Review the concept of precision oncology.

2. Explain the dimensionality problem of precision oncology. 

3. Summarize the use of different types of AI in precision oncology.

Tandem repeats are hard to assess but important regions on the human genome. There are around 200 pathogenic and phenotypic tandem repeats, which are often ignored by standard analysis. Furthermore, these tandem repeats are utilized in crime scene investigations. Given the impact of these regions, it is important that we learn more about these regions of the human genome and their role in diseases and other traits.

In this presentation, Fritz will highlight our work to comprehensively characterize 1.7 million tandem repeat regions across the entire human genome. Utilizing unsupervised machine learning we identified interesting characteristics and clustering of these regions with implications into regulation and thus medical implications. To promote the usage of tandem repeats we further generated a novel GIAB benchmark and comparison methods. These enable for the first time a comparison across different technologies or samples at scale. To promote these activities further Fritz will present their tandem repeat caller that identifies variations together with epigenetic changes in tandem repeats leveraging PacBio sequencing data. All together this presentation brings the field of human genomic and genetics forward enabling the routine assessment of benign and pathogenic tandem repeats.

Learning Objectives: 

1. Review the complexity and variety of tandem repeats for human health.

2. Review new concepts on how to identify variants and methylation simultaneously in tandem repeats.

3. Summarize the benefits of long reads for the identification of variants.

RNA is dynamic and essential to biological functions. Metatransrciptome captures gene expression (RNAs) of all active microbes in an environment. We care not just 'who is there', but also 'what they are doing'. By sequencing the metatranscriptome, we can decipher human-microbiome interactions for the prevention, early diagnosis, and treatment of chronic diseases.

This presentation will cover how an at-home non-invasive saliva based test leverages metatranscriptomic profiling for health assessment. Microbial functional pathways in the oral cavity are quantified as eight scores from saliva metatranscriptome. These scores are shown to be significantly worse in individuals with periodontal disease (gingivitis), acid reflux, and nicotine addiction, compared with controls.

Learning Objectives: 

1. Explain metatranscriptome is effective to measure both microbes and their active functions.

2. Discuss oral microbial functional pathways using saliva metatranscriptome data.

3. Demonstrate that the pathway scores are significantly worse in individuals with gingivitis and other conditions.