Jeffrey Rosenfeld described his work using tumor sequencing to personalize cancer treatment. His lab uses a targeted sequencing panel to identify driver mutations in tumors, then filters variants using software like VarSeq. Potentially actionable mutations are evaluated using databases like N-Of-One and discussed at molecular tumor boards to guide treatment. Integrating sequencing results into clinical decision making and research databases allows improving outcomes for patients.
The clinical application development and validation of cell free dna assays -...Candy Smellie
What is the impact of assay failure in your laboratory and how do you monitor for it?
In cancer patients, cell-free DNA carries tumour-related genetic alterations that are relevant to cancer development, disease progression and response to therapy.
Cell-free DNA detection allows:
Early detection
Frequent sampling
Monitoring of disease progression
Measure response to therapy
Detection of resistance mutation
Non-invasive diagnostic tool development
NGS for Infectious Disease Diagnostics: An Opportunity for Growth Alira Health
Infectious diseases are a major public health concern causing over 3.5 million deaths worldwide. Diagnosing patients as quickly and effectively as possible is crucial for managing disease outbreaks. Next-generation sequencing (NGS) provides unique capabilities to understand the genetic profile of infectious disease patients that no other technology can match.
Whole-genome metagenomics allows clinicians to take a deeper dive into pathogens by generating big-data about their characteristics. This data can be rapidly analyzed using complex bioinformatics software algorithms to achieve clinical-grade diagnostic accuracy. In a healthcare system shifting towards personalized medicine, NGS can provide clinicians the tools that they need to prescribe individualized treatments to save patients who were previously untreatable. The result is improved quality of care, better treatment regimes, and cost-saving healthcare.
Clinical Assessment In Incorporating a Personal GenomeDiego Herrera
This presentation goes in-depth in the growing field of personal genome sequencing. The advances in high-throughput DNA sequencing has made the process of mapping structural deviations in an individual's genetic totality more economical. The advantages in health care makes this technology more like to be fully integrated in medicine within the next ten years.
Extracting clinical value from next gen sequencingWinton Gibbons
It has become cliché in the clinical environment, and genetic sequencing realm, that there is a glut of sequence data. The conundrum is how to translate or transform the overabundance of data into clinically useful knowledge. This situation has only grown more acute since the introduction of next gen sequencing.
To arrive at the clinical knowledge, there needs to be a concentric series of integrated capabilities, and the necessary capacity. The core is of course the sequencing process itself, the IT tools to process it, and the human expertise. However, the essentials in the first two aspects, sequencing and IT, need to exist, and thereby create opportunities for organizations.
As there are numerable subtleties even within the essential capabilities, a single organization may not be able to develop all under one roof. Nor may certain abilities yet exist sufficiently. However, a complete ecosystem at best, or promising potential at worst, is still required.
The attached presentation illustrates the high-level transformation frameworks for this, and the subsequent translation of data to be clinically useful.
The clinical application development and validation of cell free dna assays -...Candy Smellie
What is the impact of assay failure in your laboratory and how do you monitor for it?
In cancer patients, cell-free DNA carries tumour-related genetic alterations that are relevant to cancer development, disease progression and response to therapy.
Cell-free DNA detection allows:
Early detection
Frequent sampling
Monitoring of disease progression
Measure response to therapy
Detection of resistance mutation
Non-invasive diagnostic tool development
NGS for Infectious Disease Diagnostics: An Opportunity for Growth Alira Health
Infectious diseases are a major public health concern causing over 3.5 million deaths worldwide. Diagnosing patients as quickly and effectively as possible is crucial for managing disease outbreaks. Next-generation sequencing (NGS) provides unique capabilities to understand the genetic profile of infectious disease patients that no other technology can match.
Whole-genome metagenomics allows clinicians to take a deeper dive into pathogens by generating big-data about their characteristics. This data can be rapidly analyzed using complex bioinformatics software algorithms to achieve clinical-grade diagnostic accuracy. In a healthcare system shifting towards personalized medicine, NGS can provide clinicians the tools that they need to prescribe individualized treatments to save patients who were previously untreatable. The result is improved quality of care, better treatment regimes, and cost-saving healthcare.
Clinical Assessment In Incorporating a Personal GenomeDiego Herrera
This presentation goes in-depth in the growing field of personal genome sequencing. The advances in high-throughput DNA sequencing has made the process of mapping structural deviations in an individual's genetic totality more economical. The advantages in health care makes this technology more like to be fully integrated in medicine within the next ten years.
Extracting clinical value from next gen sequencingWinton Gibbons
It has become cliché in the clinical environment, and genetic sequencing realm, that there is a glut of sequence data. The conundrum is how to translate or transform the overabundance of data into clinically useful knowledge. This situation has only grown more acute since the introduction of next gen sequencing.
To arrive at the clinical knowledge, there needs to be a concentric series of integrated capabilities, and the necessary capacity. The core is of course the sequencing process itself, the IT tools to process it, and the human expertise. However, the essentials in the first two aspects, sequencing and IT, need to exist, and thereby create opportunities for organizations.
As there are numerable subtleties even within the essential capabilities, a single organization may not be able to develop all under one roof. Nor may certain abilities yet exist sufficiently. However, a complete ecosystem at best, or promising potential at worst, is still required.
The attached presentation illustrates the high-level transformation frameworks for this, and the subsequent translation of data to be clinically useful.
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...QIAGEN
Liquid biopsies enable us to monitor the evolution of genetic aberrations in primary tumors as they shed the tumor cells into the circulation. The limitation is the ability to detect these low frequency genetic aberrations in a consistent manner to understand short- and long-term implications and how this information will be used in the clinic. This slidedeck will cover the challenges and solutions associated with multiple steps as one starts with liquid biopsy and move towards finding a new biomarker.
Analysis of Single-Cell Sequencing Data by CLC/Ingenuity: Single Cell Analysi...QIAGEN
Single-cell analysis is useful to study genetic heterogeneity between individual cells and can help in result interpretation by looking at the average behavior of a large number of cells. Applications include circulating tumor cells, cells from small biopsies and cells from in vitro fertilized embryos. In this slidedeck, we show how single cell next-generation sequencing data can be analyzed and what challenges needs to be overcome. One of the examples we use is single cell data from two colorectal cancer cell lines.
This slidedeck details two comprehensive informatics solutions — the Biomedical Genomics Workbench and Ingenuity Knowledge Base Variant Analysis platforms. We show the intuitive user interface of CLC Cancer Research Workbench and demonstrate how the rich biological content from Ingenuity Knowledge Base helps you rapidly identify critical variants in your samples.
Big Data and Genomic Medicine by Corey NislowKnome_Inc
View the webinar at: http://www.knome.com/webinar-big-data-genomic-medicine. This presentation covers an overview of genomic medicine, requirements and challenges of next-generation sequencing, bottlenecks to broader healthcare adoption, and why “we want to sequence everyone.”
Challenges and Opportunities for Digital PCR in the CLIA Laboratory of the Mo...Kate Barlow
Anthony Magliocco, Chair of Anatomical Pathology, Moffitt Cancer Center, USA
The Moffit Cancer Center is one of the largest NCI designated comprehensive free-standing cancer centers in the USA. The center has developed one of the most advanced personalized cancer medicine treatment programs in the world. This program is supported by a comprehensive and advanced CLIA molecular diagnostics. Digital PCR assays are currently being developed for several clinical applications including TKI resistance monitoring in patients with advanced lung cancer. The challenges and opportunities in deploying digital PCR into clinical practice will be discussed.
Analysis and Interpretation of Cell-free DNAQIAGEN
Identification and monitoring of cancer mutations from cell free DNA-Seq data is a key application in liquid biopsy. In this part of the webinar we will show how mutations can be best identified from this type of data and how they can be interpreted. Furthermore, potential challenges when analyzing this type of data will be discussed together with relevant strategies.
Now a day’s, pharma research is facing challenges in
deciphering molecular understanding of disease initiation,
progress and establishment as well as performance
assessment of drug molecule on such phases of disease
development. Emerging of next generation sequencing
bases molecular tools were found to be a key method for
creating genome wide genomics landscape of gene
mutations, gene expression and gene regulation events.
Although NGS is a powerful tool for molecular research but
same time it have its own technical challenges. Few major
challenges of NGS based pharmacogenomics is
summarized below
Prospects for Digital PCR in Absolute Quantification of DNA and RNAKate Barlow
Ward De Spiegelaere, Assistant Professor, Ghent University, Belgium
• Using examples of virology I will talk about the possibilities
and pitfalls of current digital PCR technology for absolute
quantification of DNA and RNA
• I will expand on a tool we developed for data driven
threshold setting in digital PCR
• I will discuss a method for normalization of RNA data in
digital PCR
March 21, 2017 - Biogazelle’s CSO prof Jo Vandesompele presented Biogazelle’s strategy and expertise to deploy RNA in liquid biopsies to further diagnostic applications and drug development at “Revolutionizing next-generation sequencing” (Antwerp, Belgium).
In contrast to general belief, a substantial part of the human protein coding transcriptome is abundantly present in the blood as extracellular mRNA, ready to exploited. Here, Jo presents probe based mRNA capture as a sensitive RNA sequencing workflow to study thousands of mRNA genes in cell-free RNA from cancer patients’ plasma. Apart from RNA abundance profiling, this type of data can also be use to detect structural RNA variants, such as somatic mutations, and RNA editing events, all known to play an important role in cancer. RNA capture sequencing enables liquid biopsy guided precision oncology, such as therapy stratification, treatment response monitoring and early detection of relapse.
Explains how Cancer Management can be made more effective using an integrated approach. From collecting data across reports to predict tumor growth and to be able to help users manage their condition through diet or therapy, the platform can be used to constantly track and monitor outcomes.
In this OncomineWorld 2021 presentation, learn how next-generation sequencing is playing a crucial role in cancer research. To watch the full presentation, visit www.oncomine.com/events.
In this presentation we showcase the latest advancements in myeloid genomic profiling: The Ion Torrent Oncomine Myeloid Assay GX.
Learn how this solution addresses key challenges in myeloid molecular testing and see recent data from the University of Pennsylvania.
Learn more at www.oncomine.com/myeloid
MM-KBAC – Using Mixed Models to Adjust for Population Structure in a Rare-var...Golden Helix Inc
Confounding from population structure, extended families and inbreeding can be a significant issue for burden and kernel association tests on rare variants from next generation DNA sequencing. An obvious solution is to combine the power of a mixed model regression analysis with the ability to assess the rare variant burden using methods such as KBAC or CMC. Recent approaches have adjusted burden and kernel tests using linear regression models; this method adjusts for the relatedness of samples and includes that directly into a logistic regression model.
Θρησκευτικά ήθη και έθιμα στο Νέο Σκοπό Σερρών.
Συνεργάστηκαν οι μαθητές της Α΄1 τάξης του Γυμνασίου
Ν. Σκοπού Σερρών: Χρήστος Βασιλάκης, Δημήτρης Καραμπατζάκης, Γιώργος Μπεχτσής, Χρυσοβαλάντης Μπεχτσής.
Step by Step, from Liquid Biopsy to a Genomic Biomarker: Liquid Biopsy Series...QIAGEN
Liquid biopsies enable us to monitor the evolution of genetic aberrations in primary tumors as they shed the tumor cells into the circulation. The limitation is the ability to detect these low frequency genetic aberrations in a consistent manner to understand short- and long-term implications and how this information will be used in the clinic. This slidedeck will cover the challenges and solutions associated with multiple steps as one starts with liquid biopsy and move towards finding a new biomarker.
Analysis of Single-Cell Sequencing Data by CLC/Ingenuity: Single Cell Analysi...QIAGEN
Single-cell analysis is useful to study genetic heterogeneity between individual cells and can help in result interpretation by looking at the average behavior of a large number of cells. Applications include circulating tumor cells, cells from small biopsies and cells from in vitro fertilized embryos. In this slidedeck, we show how single cell next-generation sequencing data can be analyzed and what challenges needs to be overcome. One of the examples we use is single cell data from two colorectal cancer cell lines.
This slidedeck details two comprehensive informatics solutions — the Biomedical Genomics Workbench and Ingenuity Knowledge Base Variant Analysis platforms. We show the intuitive user interface of CLC Cancer Research Workbench and demonstrate how the rich biological content from Ingenuity Knowledge Base helps you rapidly identify critical variants in your samples.
Big Data and Genomic Medicine by Corey NislowKnome_Inc
View the webinar at: http://www.knome.com/webinar-big-data-genomic-medicine. This presentation covers an overview of genomic medicine, requirements and challenges of next-generation sequencing, bottlenecks to broader healthcare adoption, and why “we want to sequence everyone.”
Challenges and Opportunities for Digital PCR in the CLIA Laboratory of the Mo...Kate Barlow
Anthony Magliocco, Chair of Anatomical Pathology, Moffitt Cancer Center, USA
The Moffit Cancer Center is one of the largest NCI designated comprehensive free-standing cancer centers in the USA. The center has developed one of the most advanced personalized cancer medicine treatment programs in the world. This program is supported by a comprehensive and advanced CLIA molecular diagnostics. Digital PCR assays are currently being developed for several clinical applications including TKI resistance monitoring in patients with advanced lung cancer. The challenges and opportunities in deploying digital PCR into clinical practice will be discussed.
Analysis and Interpretation of Cell-free DNAQIAGEN
Identification and monitoring of cancer mutations from cell free DNA-Seq data is a key application in liquid biopsy. In this part of the webinar we will show how mutations can be best identified from this type of data and how they can be interpreted. Furthermore, potential challenges when analyzing this type of data will be discussed together with relevant strategies.
Now a day’s, pharma research is facing challenges in
deciphering molecular understanding of disease initiation,
progress and establishment as well as performance
assessment of drug molecule on such phases of disease
development. Emerging of next generation sequencing
bases molecular tools were found to be a key method for
creating genome wide genomics landscape of gene
mutations, gene expression and gene regulation events.
Although NGS is a powerful tool for molecular research but
same time it have its own technical challenges. Few major
challenges of NGS based pharmacogenomics is
summarized below
Prospects for Digital PCR in Absolute Quantification of DNA and RNAKate Barlow
Ward De Spiegelaere, Assistant Professor, Ghent University, Belgium
• Using examples of virology I will talk about the possibilities
and pitfalls of current digital PCR technology for absolute
quantification of DNA and RNA
• I will expand on a tool we developed for data driven
threshold setting in digital PCR
• I will discuss a method for normalization of RNA data in
digital PCR
March 21, 2017 - Biogazelle’s CSO prof Jo Vandesompele presented Biogazelle’s strategy and expertise to deploy RNA in liquid biopsies to further diagnostic applications and drug development at “Revolutionizing next-generation sequencing” (Antwerp, Belgium).
In contrast to general belief, a substantial part of the human protein coding transcriptome is abundantly present in the blood as extracellular mRNA, ready to exploited. Here, Jo presents probe based mRNA capture as a sensitive RNA sequencing workflow to study thousands of mRNA genes in cell-free RNA from cancer patients’ plasma. Apart from RNA abundance profiling, this type of data can also be use to detect structural RNA variants, such as somatic mutations, and RNA editing events, all known to play an important role in cancer. RNA capture sequencing enables liquid biopsy guided precision oncology, such as therapy stratification, treatment response monitoring and early detection of relapse.
Explains how Cancer Management can be made more effective using an integrated approach. From collecting data across reports to predict tumor growth and to be able to help users manage their condition through diet or therapy, the platform can be used to constantly track and monitor outcomes.
In this OncomineWorld 2021 presentation, learn how next-generation sequencing is playing a crucial role in cancer research. To watch the full presentation, visit www.oncomine.com/events.
In this presentation we showcase the latest advancements in myeloid genomic profiling: The Ion Torrent Oncomine Myeloid Assay GX.
Learn how this solution addresses key challenges in myeloid molecular testing and see recent data from the University of Pennsylvania.
Learn more at www.oncomine.com/myeloid
MM-KBAC – Using Mixed Models to Adjust for Population Structure in a Rare-var...Golden Helix Inc
Confounding from population structure, extended families and inbreeding can be a significant issue for burden and kernel association tests on rare variants from next generation DNA sequencing. An obvious solution is to combine the power of a mixed model regression analysis with the ability to assess the rare variant burden using methods such as KBAC or CMC. Recent approaches have adjusted burden and kernel tests using linear regression models; this method adjusts for the relatedness of samples and includes that directly into a logistic regression model.
Θρησκευτικά ήθη και έθιμα στο Νέο Σκοπό Σερρών.
Συνεργάστηκαν οι μαθητές της Α΄1 τάξης του Γυμνασίου
Ν. Σκοπού Σερρών: Χρήστος Βασιλάκης, Δημήτρης Καραμπατζάκης, Γιώργος Μπεχτσής, Χρυσοβαλάντης Μπεχτσής.
The premedical competencies as outlined in a recent American Association of Medical Colleges (AAMC)-HHMI report on Scientific Foundation for Future Physicians calls for stronger connections between course content and the underlying principles in health and medicine. To meet this need, I am developing chemistry courses at the University of Illinois for pre-health professionals that teach concepts and content in a personally meaningful way, thereby stimulating deep student interest and promoting curiosity-driven learning. Scientific evidence shows that people who feel curious devote more attention to an activity, process information more critically, remember information more effectively and persist on task until goals are met.
Στα πλαίσια του μαθήματος της Αρχαίας Ελληνικής Ιστορίας,
οι μαθήτριες της Α΄1 τάξης του γυμνασίου Νέου Σκοπού, Καμακάμη Ευαγγελία και Κουζουτζίδου Παρασκευή,παρουσιάζουν τη Διατροφή στην Αρχαία Ελλάδα
Disabilities in Israel - Facts and Figures 2013mjbinstitute
An updated compendium of statistics and information on the population with disabilities in Israel, developed jointly by JDC-Israel Unlimited and the Myers-JDC-Brookdale Institute.
Οι μαθητές της Β΄1 τάξης του Γυμνασίου Νέου Σκοπού Σερρών με αφορμή το κείμενο της Νεοελληνικής Λογοτεχνίας,
"Ο μικρός πρίγκιπας και η αλεπού" του Αντουάν ντε-Σαιντ Εξυπερύ, μιλούν για την αληθινή φιλία.
Οι μαθήτριες της Α΄2 τάξης, Τσώνη Σταυρούλα, Ράντου Χρύσα και Σέκρα Σοφία, ζωγραφίζουν και δραματοποιούν τη συνομιλία του Τηλέμαχου με την Αθηνά- Μέντη
Making a Difference Through Research: Myers-JDC-Brookdale 40th Anniversary Br...mjbinstitute
Celebrating 40 years of the Myers-JDC-Brookdale Institute, with testimonials from key partners and highlights of research impacts. Learn how MJB has used applied socal research to help shape Israel's social policy and social service landscape since 1974.
Leadership for Affordable Housing Evaluation Studymjbinstitute
The Leadership Program for Affordable Housing is a multi-sectoral program that was created in the context of the sharp increase in housing costs incurred by Israeli households and the belief that a concerted multi-sectoral effort is required to address the challenge.
The program was a collaboration between the Ministry of Construction and Housing and the JDC Institute for Leadership and Governance, together with senior level professional representatives from ten ministries and government agencies, local government, civil society organizations and the business sector.
It was implemented under the professional guidance of Dr. Chaim Fialkoff and Dr. Emily Silverman.
The Myers-JDC-Brookdale Institute was commissioned to evaluate the program. For more information on this or other MJB research studies, please contact us at brook@jdc.org, visit our webpage at http://brookdale.jdc.org.il/ or catch us on Facebook at https://www.facebook.com/MJBInstitute
Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) from patient plasma is becoming more widespread in oncology clinical trials. The noninvasive nature of acquiring these samples is particularly important when resection of representative tumor samples is not advised or not possible. However, profiling of ctDNA has challenges to overcome, such as low concentration of ctDNA shed from the tumor and a low signal:noise ratio caused by somatic alterations with less than 1% variant allele fraction. Improving the sensitivity of these assays to detect low allele frequency events with high confidence requires robust sequencing of low input libraries while employing error correction to reduce background noise. To overcome these challenges, we have incorporated unique molecular identifiers (UMIs) into our NGS workflow. Using these novel adapters paired with our proprietary bioinformatics pipeline (AstraZeneca), the number of false positive variants reported for allele fractions less than 0.5% was reduced tenfold. We also refined our curation based on the mapping quality and strand bias in the vicinity of each variant to further reduce the background noise. The use of xGen® Dual Index UMI Adapters—Tech Access (Integrated DNA Technologies) has enabled us to sequence thousands of plasma samples from diverse tumor indications and at differing time points during our trials. The generated data are highly informative with the potential to answer critical questions relating to individual response or resistance to experimental therapies. During this webinar, we discuss our current NGS ctDNA workflow and our future plans to increase our sequencing sensitivity with these novel UMI adapters.
Developing a framework for for detection of low frequency somatic genetic alt...Ronak Shah
Cancer is a complex, heterogeneous disease of the genome. Most cancers result
from an accumulation of multiple genetic alterations that lead to dysfunction of cancer-associated
genes and pathways. Recent advances in sequencing technology have enabled comprehensive
profiling of genetic alterations in cancer. We have established a targeted sequencing platform
(IMPACT: Integrated Mutation Profiling of Actionable Cancer Targets) using hybridization capture and
next-generation sequencing (NGS) technology, which can reveal mutations, indels and copy number
alterations involving 340 cancer related genes.
Next Generation Companion Diagnostics; Adoption, Drivers, and Moderators of N...Andrew Aijian
Analysis and synthesis of a pulse survey conducted across >140 oncologists, pathologists, and lab directors regarding current adoption and trends associated with emerging oncology biomarkers and companion diagnostics (CDx), with an emphasis on next-generation sequencing (NGS)-based CDx.
Acibadem City Clinic Cancer Center is a modern specialized medical facility for cancer patients. The structure comprises of departments and clinics in Medical oncology, Radiation Oncology, Nuclear Medicine, Radiology and Imaging Diagnostics, Gastroenterology and Clinical Pathology. Chemotherapy, targeted therapy, rehabilitation and psychological support for the patients and their families. Patients have access to cutting-edge technologies such as PET / CT and SPECT / CT imaging, 3D mammography with tomosintesis, robot for automated mixing of medicines and many others. The leading specialists in the hospital are reknown and certified in famous clinics in Europe and around the world.
Update on the Adoption and Utilization of Emerging Precision Medicine Biomark...Andrew Aijian
In this 2nd wave of our precision oncology pulse survey, we explore how recent clinical, commercial, and regulatory events have impacted the adoption of emerging precision oncology biomarkers and diagnostic tools. We also examine the key technological trends likely to impact the landscape in the near-mid term.
di Pier Giuseppe Pelicci, MD-PhD, Istituto Europeo di Oncologia IEO, Università degli Studi di Milano.
Slide per l'intervento tenuto in Fondazione Giannino Bassetti in occasione del primo incontro del ciclo "La medicina di precisione", primo progetto dalla convenzione tra Università di Pavia e Fondazione Bassetti.
12 marzo 2018
Similar to Personalized Medicine through Tumor Sequencing (20)
Two Clinical Workflows - From Unfiltered Variants to a Clinical ReportGolden Helix Inc
Clinical labs need to be able to process samples down to a short list of variants and publish a professional report. Two common clinical applications for genetic tests include Cancer Gene Panels and Whole Exome Trios. Using VarSeq and VSReports, we will demonstrate how easy it is to go from a variant file created by a secondary analysis pipeline containing unfiltered variants to a report containing information for variants of interest. Along the way we will discuss tips and tricks and answer frequently asked questions to help you get the most out of your data!
We are excited to announce and demonstrate some new and highly requested features in this webcast, including predicting phenotypes by applying existing GBLUP or Bayesian models and meta-analysis for GWAS studies.
Using VarSeq to Improve Variant Analysis Research WorkflowsGolden Helix Inc
In this webinar presentation, we will review workflow strategies for quality control and analysis of DNA sequence variants using the VarSeq software package from Golden Helix. VarSeq is a powerful platform for analysis of DNA sequence variants in clinical and translational research settings. VarSeq provides researchers with easy access to curated public databases of variant annotation information, and also enables users to incorporate their own local databases or downloaded information about variants and genomic regions.
Genome-wide association studies (GWAS) have been providing valuable insight to the genetics of common and complex diseases for many years. In this webcast we will walk through one possible workflow for completing GWAS in Golden Helix SNP & Variation Suite (SVS) with special attention paid to adjusting analysis for population stratification.
Introducing VSWarehouse - A Scalable Genetic Data Warehouse for VarSeqGolden Helix Inc
As Precision Medicine is taking off, the number of samples in a testing lab and the associated data volume is increasing exponentially. In order to organize the data and build a knowledge base of cases that can be used for future analysis as well as ongoing research, labs need to leverage state of the art warehousing technology.
Clinical labs must have the ability to go from a collection of samples and associated variants to a professional report documenting a short list of clinically relevant variants. Cancer Gene Panels are a common clinical application for genetic tests. In this webcast we will show how VarSeq and VSReports can be used to go from an unfiltered variant file created by a secondary analysis pipeline to a report containing information about interesting variants.
Getting Started with VSWarehouse - The User ExperienceGolden Helix Inc
Built on the algorithms and high-performance storage technology that powers the VarSeq software, VSWarehouse offers a scalable, multi-project warehouse for NGS variant call sets, clinical reports, and a knowledge base of variant classifications.
In this presentation we will demonstrate how to customize your VarSeq workflow to handle the following family scenarios:
*Full Quad (mother, father and 2 affected children)
*Siblings with different affection status (mother, father, 1 affected and 1 unaffected child)
*No parents (2 affected siblings)
Using Clinical Reports as a part of a Gene Panel PipelineGolden Helix Inc
This webcast will walk through preparing a template for automatic report generation, running new data through the pipeline and reviewing the generated report.
Big Data at Golden Helix: Scaling to Meet the Demand of Clinical and Research...Golden Helix Inc
With a focus on scalable architecture and optimized native code that fully utilizes the CPU and RAM available, we can scale genomic analysis into sizes conventionally considered Big Data on a single host. In this webcast, we demonstrate recent innovations and features in Golden Helix solutions that enable the analysis of big data on your own terms.
Join us in this webcast to see how we have written an open-source C++ port of Beagle v4.1 that is fully integrated into SVS and allows you to run your genotype phasing and imputation on human and animal data as part of your SVS analytics workflow.
Population Structure & Genetic Improvement in LivestockGolden Helix Inc
The genetic improvement of livestock has been a hot topic for almost a century, bringing together researchers, industry, and producers to work towards a common goal. Many countries currently employ extensive genetic selection programs in their cattle with pigs, sheep, and chicken close behind.
In this webcast, Heather J. Huson, Ph.D. from Cornell University will focus on population dynamics and trait association in cattle and goats using high density SNP datasets. Population structure plays a critical role in understanding the relatedness among livestock, ancestral origins of traits, and identification of unique sub-populations or breeds for production improvement and conservation. This also lays the foundation for understanding and improving species such as the goat which is a vital food source in developing countries but has little recorded production or health data.
Understanding population structure is essential for designing complex trait association studies such as those related to production and health characteristics. Here, Huson shows examples of her lab's investigation into population structure in both goats and cattle to identify distinct groups and study traits such as thermo-tolerance.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
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This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
2. My Background
I am an Assistant Professor of Pathology and Laboratory Medicine at the
Rutgers Robert Wood Johnson Medical School
I supervise the computational aspects of the Precision Medicine Initiative at
Rutgers University Cancer Institute of New Jersey (CINJ) in addition to
working in the bioinformatics core
We are the only NCI Designated Comprehensive Cancer Center in NJ
I have been working with Golden Helix software since 2009. First with SVS
and now with VarSeq
3. Cancer
Traditionally cancer has been treated with chemotherapy with all of its harsh
effects
Treatment was mainly focused on the site of a tumor
Since cancer is caused by mutations driving tumor growth, targeting those
mutations should control the cancer
Starting in 2001, focused drugs such as imatinib/Gleevec, have been developed
▪ Targets the bcr-abl fusion protein in chronic myelogenous leukemia (CML)
BRAF V600E
▪ Mutated in a significant percentage of cancers, especially melanoma
4. We are realizing that cancer is many diseases not one disease
Individual patients have unique tumors and the treatment should be
personalized
pancan.org, thegrouproom.tv,mycancergenome.org
5. Druggable Mutations
Currently, there are 70 drugs FDA approved for targeted cancer treatment
▪ Some of these drugs are highly similar and simply competing products
In many cases, the drug will be approved for one type of cancer, but doctors
will prescribe it off-label for other types of cancer
A large number of drugs are currently making their way through clinical
trials
▪ Genetic testing is helping to be targeted in trials
7. Determining Mutations in a Tumor
When sequencing is performed, it can use either a tumor-only or a tumor-normal
approach
▪ Can be drivers or passengers
The number of sequenced tumors is rapidly growing and it may limit the need for
sequencing a matched normal
▪ TCGA - 11,000 samples
▪ ICGC - 17,867 samples
Sequencing a tumor and a matched normal sample is twice as expensive as just
doing the tumor
Tumor
Mutations - Germline
Mutations = Mutations only
in the Tumor
9. Commercial Lab
1. Tumor biopsy samples are sent to an outside lab for processing
The lab does all of the work including billing
Easy to implement, but no possibility of customization
Hard to get access to the raw BAM files for research
11. In-house
2. Develop everything in-house
Example: Memorial Sloan Kettering MSK-IMPACT
Test is a custom designed panel of genes
Analysis software is maintained by a team of local developers
Database of mutations is curated by local scientists
Allows for complete control over the data
Requires a large investment of time and a substantial amount of
individuals with a wide range of skills
12. Hybrid Approach
3. Run the test locally, using different commercial parts
Companies have developed specialized products including target panels,
analysis software and annotation databases
Lesser requirement of resources than developing everything locally
Maintain control of the data
Not relying simply on a “black-box” for the testing
14. Our Pipeline in a Nutshell
RainDance Thunderbolts Cancer Panel
MiSeq
BaseSpace
VarSeq
N-Of-One
Designed to be a low-cost primary test
Patients who do not receive a test result beneficial to their treatment can be
relaxed to a larger panel
15. RainDance
Enriches the genome for mutational hotspots in 50 top cancer genes
Droplet PCR allows for even amplification
Total of ~200 amplicons
All amplicons together only equal <40kb of DNA
Does NOT cover full genes or even all exons, only hotspots
16. Sequencing and primary analysis
Samples can be multiplexed to put 8 on a single Mi-seq run
Keeps the costs down as compared to the need for a HiSeq lane for other
panels
Alignment and variant calling are performed using BaseSpace using standard
tools
Only SNPs and indels can be called
No fusions, amplifications or deletions can be detected
Calls the most highly studied tumor mutations
17. Data transfer
Extensive infrastructure is needed to maintain CLIA/CAP and HIPPA compliance
The sequencing lab and the analysis machines are located on different networks
with intervening firewalls
BAM and VCF files need to be encrypted to be copied
Transfer is automatic based upon a daemon recognizing files in a designated
directory
Data files are automatically replicated archived for mandated long-term storage
18. Analysis Software Tradeoffs
Commercial vs. Open source
Robust support from professionals
Software will exist beyond the timeline of a graduate student or postdoc
Need to pay for the software
Graphical vs. Command Line
Usability for a clinician or technician without extensive computational skills
Potential for a bioinformatician to automate jobs and build pipelines
Pay-per-sample vs. License model
Set cost that can be built into a medical bill
Fixed annual expenditure
No need to pay for re-running of samples or for non-billable/research samples
19. VarSeq
Produced by Golden Helix
A graphical interface to filter variants and to classify them using public and
private data
Roughly equivalent to what can be done using ANNOVAR or VAAST, but with
a graphical interface (GUI)
A command-line version is available where the analysis parameters can be set up
in the GUI, but run automatically from a script
Software is highly configurable by the user
Can process our samples in < 1 minute each
A full genome or exome will take a few minutes or longer to process
Reduces the number of variants we find in a tumor from hundreds to <10
Software is purchased as an annual license rather than paying per-sample
At Rutgers we were very attracted to the annual license model
Allows us to run research samples without worrying about the cost
20. Variant Filtering
The raw VCF has >100 variants called for each tumor
Most of these variants are not important in the treatment of the cancer
Could be germ-line variants
Could be passenger mutations from highly mutating tumors
Variants could have low read depth
Could reflect sequencer errors
Minor allele frequency could be very low
Variant could be noise
A mutation only found in a very small proportion of the tumor sequencing
reads is not an important clinical target
21. Filtration
Passes the standard BaseSpace filters
Read Depth is > 1000X
Minor allele frequency is > 0.05
Not found in the >=1% in any 1000 Genomes population
Non-synonymous
Not a known false positive from the assay
25. Clinical evaluation of variants
After the variant list is narrowed down, there is a need to determine whether
the variants are clinically actionable
Literature on variants is continually changing
Hundreds of papers are published each week
Clinical Trials are constantly opening and closing
Trials can have very strict criteria for accepting patients
Patients have different geographical constraints on where they can travel
for treatment
27. N-Of-One
Instead of needing to maintain a database of publications and trials, we
outsource to N-Of-One
Provided the analysis for Foundation Medicine several years
Company maintains a thorough database of literature and clinical trials
relating to genome variants
28. N-Of-One
Data is exported from VarSeq as a text or Excel file and then converted to
XML
We transfer our results to them using XML and they identify all known
clinical information about a variant
Report is returned to us as XML and used to generate a signed clinical report
for physicians
Results are returned within a few hours for known mutations, but may
require a few days for a novel mutation
29. Reporting
The annotations from N-Of-One are reviewed by the Molecular Pathologist
and a final signed report is generated
This report becomes part of the patient’s electronic medical record (EMR)
and is used to help determine their treatment
31. Molecular Tumor Board
At CINJ, we have a weekly molecular tumor board where oncologists,
pathologists, and bioinformaticians review the findings from the molecular
testing
With all of the professionals working together, and taking into account the
patient’s condition, we determine the proper course of treatment
32. Clinical Data Warehouse
The molecular test results along with diagnostic and treatment data from the
EMR and histology images are collected into a database
This data can be queried to ask innovative research questions on the
population of patients
How well did breast cancer patients with a particular mutation do on a
specific drug?
Can we better determine which mutations should be targeted by specific
drugs by using a set of mutations rather than just a single mutation?
33. Summary
Clinical Tumor Sequencing is dramatically changing cancer treatment
There are a large number of computational steps that are needed for doing
clinical tumor sequencing
Through the use of these panels, we have greatly enhanced the outcomes for
our patients.