New & Improved COSMIC Database for NGS Cancer Analyses
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With Next-Gen Sequencing becoming a routine method of rapidly investigating cancer mutations, having access to accurate and large somatic variant catalogs is paramount. We at Golden Helix are excited to announce our newly released COSMIC 87 track. This updated version of the world's largest and most comprehensive somatic track provides a number of significant improvements. This includes not only an increase of ~1.1 million variants but also improvements on evidence accessibility and as always maintaining data quality. As a result of our 20+ years of bioinformatics experience, users have come to trust and rely on our data curation since our goal is to ensure highly efficient and accurate variant analysis. With this webcast, we are going to focus on the new capabilities users have when integrating COSMIC into their cancer workflow. We will also discuss the implications and value of relying on top data quality data curation maintained here at Golden Helix. Please join us as we seek to inform you on methods to optimize your cancer variant analysis!
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New & Improved COSMIC Database for NGS Cancer Analyses
- 1. Darby Kammeraad – FAS Manager New and Improved COSMIC Database for NGS Cancer Analysis
- 2. NIH Grant Funding Acknowledgments Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: - Award Number R43GM128485 - Award Number 2R44 GM125432-01 - Award Number 2R44 GM125432-02 - Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 PI is Dr. Andreas Scherer, CEO Golden Helix. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 3. Q & A Please enter your questions into your GoToWebinar Panel
- 4. Golden Helix – Who We Are Golden Helix is a global bioinformatics company founded in 1998 CNV Analysis GWAS Genomic Prediction Large-N Population Studies RNA-Seq Large-N CNV-Analysis Variant Warehouse Centralized Annotations Hosted Reports Sharing and Integration Filtering and Annotation ACMG Guidelines Clinical Reports CNV Analysis Pipeline: Run Workflows
- 5. Cited in over 1,400 peer-reviewed publications
- 6. Over 400 customers globally
- 7. Golden Helix – Who We Are When you choose a Golden Helix solution, you get more than just software REPUTATION TRUST EXPERIENCE INDUSTRY FOCUS THOUGHT LEADERSHIP COMMUNITY TRAINING SUPPORT RESPONSIVENESS INNOVATION SPEED
- 8. VarSeq Clinical Workflows Stack
- 9. NGS-based Cancer Analysis Sanger Institute COSMIC VarSeq Analysis and Demo Q/A Agenda
- 10. Cancer Analysis In 2018, ~ 18 million new cases of cancer occurred globally (National Cancer Inst 2018) - 9.5 million deaths globally Financial cost of cancer = $1.16 trillion per year as of 2010 (World Cancer Report 2014) Oncology is an iconic example for the value of clinical genomics testing* - Testing can improve outcomes for cancer patients: better treatment plans, diagnosis, and prognosis - NGS test range from targeted “hotspot” panels to WES or genome scale platforms How does GHI software fit in? - From “hotspot” panels up to WGS data; you need easy, accurate, comprehensive tertiary analysis capability - VarSeq is the clinical tertiary analysis solution - Provides top quality curated cancer annotations and many more.. - COSMIC, ICGC, CIViC, and more to come! *Zehir et al. Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 patients. Nat Med. 2017; 23-703-13
- 11. Wellcome Sanger Institute* British center of genomic diversity - Opened in 1993 - World leader in genome research: - DNA Seq - Cellular genetics - Mouse genetics - Research areas - Cancer, aging, somatic mutations - Cellular genetics - Human genetics - Parasites and microbes *https://www.sanger.ac.uk/
- 12. COSMIC Catalog of Somatic Mutations in Cancer - Recent update to v87 - Now over 3.2 million variants: increase of ~1.1 million variants - 4 new fully curated genes: ARID1B, RBM10, B2M, BCORL1 - Curation updates for mesothelioma, KRAS, gene fusions, resistance mutations, and whole genome data. - COSMIC team manual curation process - Provides improved quality control over systematic approaches - Controls for inconsistencies or errors in publications - Accurate frequency data In VarSeq: New filter criteria - Now includes frequency counts - Tissue, site, histology, sample, zygosity, somatic status, tumor origin - PubMed IDs
- 13. VarSeq Project Somatic mutation search - Variant filtering and prioritization: - Variant quality - Presence in COSMIC - Potentially pathogenic - Investigate two example variants - First obvious pathogenic: KRAS common oncogene - Second likely pathogenic: EGFR receptor protein – proto-oncogene
- 14. Demonstration
- 15. Q & A Please enter your questions into your GoToWebinar Panel
- 16. Abstract Competition – Don’t forget to enter! All testing labs, hospital labs, academic, government or commercial organizations who are Golden Helix users are invited to apply Enter our abstract competition for a chance to win our great prizes: - First Place: One-year SNU license of SVS or VarSeq, Dell laptop, webcast presentation - Second & Third Place: One-year SNU license of SVS or VarSeq, webcast presentation Enter on our website, applications accepted until January 30th
- 17. Secondary Analysis 3.0 New, updated version! Many other eBooks on our site
- 18. PAG XXVII – Plant & Animal Genome Conference January 12-16, 2019 – San Diego, CA Visit us in booth #116 for demos and t-shirts!
- 19. Thank you! Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: - Award Number R43GM128485 - Award Number 2R44 GM125432-01 - Award Number 2R44 GM125432-02 - Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 PI is Dr. Andreas Scherer, CEO Golden Helix. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- 20. Q & A Please enter your questions into your GoToWebinar Panel
Editor's Notes
- Before getting started with todays content, we at Golden Helix would like to give a massive thank you to the NIH for their grant support. The Research reported in this publication was supported by the National Institute General Medical Sciences of the National Institutes of Health under the following awards. Our PI is our CEO at Golden Helix, Dr. Andreas Scherer, and the content today is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Again, thank you very much for the financial support.
- Also, before we deep dive, I’d like to remind our viewers to enter any questions into the questions panel in GoToMeeting.
- GoldenHelix is a global bioinformatics software and analytics company that enables research and clinical practices to analyze large genomic datasets. We were originally founded in 1998 based of pharmacogenomics work performed at GalxoSmithKline who was and still is a primary investor in our company. We currently have two flagship products Varseq and SNP and Variation Suite (SVS) for short. SVS is our research application platform that enables researchers to perform complex analysis and visualizations on genomic and phenotypic data. SVS has a broad range of tools to easily perform GWAS, Genomic Prediction, Differential expression analysis on RNA-Seq Data and has the ability to process CNV analysis, which we will demonstrate today. VarSeq, on the other hand, is our clinical application platform that is used for filtering and annotating variants of interest. We can also evaluate variants according to the ACMG guidelines with VSCLincal and have the option to automatically create clinical reports from the results of various workflows. Using the same software, we can also perform CNV analysis on targeted gene panels and whole genome sequencing, which we will demonstrate today and We also have an add-in function called VSPipeline – which can take the workflow that you created and automates the process with very little human interaction. Now all of the information produced from VarSeq can be stored in our Warehouse solution, which is designed to be installed on a server location and serve as a repository for your variants evaluations, annotations, and hosted reports. Lastly, VSWarehouse can also be implemented for sharing and integration between license holders.
- Our software has been very well received by the industry. We have been cited in over 1300 peer-reviewed publications
- Global We work with over 350 organizations that can be categorized into 5 groups comprising of pharmaceutical companies, Bayer and Lilly top-tier institutions, Stanford and yale government organizations, NCI clinics, Sick kids genetic testing labs, prevention genetics and lineage Approaching 10,000 installs of our products and have 1,000’s of unique users. So why is this relevant to you.
- Well what that means to you is that over the course of 20 years our products have received a lot user feedback, which we are always very receptive to when developing and releasing newer versions of our products. This user feedback allows our software to stay relevant and well vetted in it’s capabilities and qualities which builds our products reputation, trust, and client experience. We also stay on the forefront of the needs of the industry and community by regularly attending conferences and providing useful product information via eBooks, tutorials, and blog posts. Golden Helix is on the leading edge in today’s competitive environment and strives to provide a software that is innovative and fast for all of your data analysis. But one of the greater values that comes with the license is the Service. Training and support are included in our packages and Our team of experts are available to provide the resources needed to help complete your analysis. Ultimately, we aim to support our customers every step of the way.
- First and foremost, any presentation on COSMIC as an annotation for somatic variants warrants a discussion on the value of performing NGS based cancer analysis. Once we cover some major highlights, we will talk about what is new with the recent COSMIC update, explore a project in VarSeq that demonstrates the software usability and exploration of COSMIC content, then share some valuable insight on GHI quality standards for database curation. Then to wrap things up, we will work to answer any of our viewers questions
- So, if we take a step back for a minute, let’s get a framework of the need for NGS-based analysis in oncology. In 2018 there were approximately 18.1 million new cancer cases reported around the globe. More importantly, we saw 9.5 million cancer related deaths globally that year. We take cancer extremely seriously and as of 2010 we’ve spent 1.16 trillion dollars for research and treatment around the world. NGS Based analysis is a huge benefit to oncology especially since such a large number of cancers are due to genomic changes. This is relevant whether you are investigating targeted gene panels on known cancer genes, whole exome data, or even across an entire genome. So this is where the value of VarSeq really shines, allowing users to assess mutations across all genomic landscapes, gene panels to whole genome. The tertiary analysis is performed by stacking annotations against each variant, and in this case COSMIC is one among many cancer related tracks we curate. Let’s take a look at what the updated COSMIC track provides.
- We wouldn’t be able discuss the value and application of known somatic mutations in COSMIC without recognizing all the effort put forth from the Sanger institute to provide this data. The sanger institute has made huge contributions in genome research and provide many foundations for further research in human and pathogen biology. The work done at Sanger can be organized into key programs that include the focus of todays webcast, cancer and somatic mutations as well as cellular genetics, human genetics and parasites and microbes. As quoted on their site Sanger is conceptually an idea engine driven by a collective of imaginative scientists with a shared commitment to understanding genomes and their biological implications, with competencies and experience in their analysis, but with diverse expertise in everything from biology and genetics, medicine, mathematics and computer science. It is worth giving a sincere thank you to Sanger for all of their hard work, of which we will only cover a fraction of today.
- With the most recent version 87 release, users gain access to over 1.1 million new variants in VarSeq. From the COSMIC end on updates, users will see 4 new genes added, more detailed curation for mesothelioma, KRAS, gene fusions, resistance mutations, and whole genome data. The COSMIC team worked hard to improve quality control on the curation process overall, correcting inconsistencies or errors in publications as well as provide accurate frequency data. From the VarSeq side, users have access to the new frequency count data that can be used for filtering, and also easy access to the publication information available for each variant. In the demonstration, I will show you where you go to access this premium annotation, and use the fields in COSMIC to build a simple workflow to filter known somatic variants.
- In the project, I have imported a set of variants and filtered through them with a simple workflow that not only captures high quality/true positive variants, but also those known somatic variants in COSMIC, and any that may be pathogenic. We are also going to deep dive into a couple variants through the ACMG guidelines in VSClinical. VSClinical is a great interactive display of many annotations and variant scoring details that allows us to understand the intricacies of how a variant interacts with a gene. The two example variants I will cover will include a straightforward assessment of a pathogenic variant in KRAS, as well as a more challenging EGFR missense variant that will best demonstrate the value that COSMIC adds to variant clinical significance.
- The ACMG guidelines provide a set of criteria to score variants and place them into one of five classification tiers. Following the guidelines requires diving into the annotations, genomic context and existing clinical assertions about every variant. VSClinical provides a tailored workflow to score each relevant criterion, while also providing all the bioinformatic literature and evidence from clinical knowledgebases. This includes population frequencies, functional prediction scores, conservation scores, and effect prediction. Through standardized questions, automatically computed evidence, and historical context, VSClinical provides clinicians with everything they need to reach a final classification consistently and reproducibly, thereby reducing the subjectivity of the variant classification process. While a final classification of a variant requires the manual inspection of the sample’s clinical details, published literature and the content of existing related clinical interpretations, many criteria from the ACMG guidelines can be automatically computed with bioinformatic algorithms and specially curated annotation sources. The work done in your lab to classify variants will be automatically included in future analyses. As the number of samples processed increases, the number of variants requiring classification will be reduced, along with sample turn-around time. Previously classified variants will be marked with their last evaluation date, allowing them to be accepted in the context of the current sample without extra analysis time. Look at 16 and 12