--- title: Diagnostic Precision Blog | Yves Konigshofer, PhD description: A SeraCare blog focused on precision medicine and advanced clinical diagnostics --- [![SeraCare](https://blog.seracare.com/hs-fs/hubfs/0.%20Logos/SeraCare/SeraCare.png?width=400&name=SeraCare.png "SeraCare")](https://www.seracare.com) - [Home](https://blog.seracare.com/ngs) - [About](https://digital.seracare.com/about-blog) - [News and Events](http://www.seracare.com/NewsEvents/NewsCenter/tabid/354/Default.aspx) - [Contact](http://www.seracare.com/Contact/tabid/366/Default.aspx) ## [Diagnostic Precision](https://blog.seracare.com/) A SeraCare blog focused on precision medicine and advanced clinical diagnostics Choose your Article Focus | [NGS](https://blog.seracare.com/ngs) | [Molecular & Serology](https://blog.seracare.com/molecular-serology-blog) ## Yves Konigshofer, PhD ### Recent Posts ## [Development of a Novel Reference Material for MRD Monitoring Assays](https://blog.seracare.com/ngs/development-of-a-novel-reference-material-for-mrd-monitoring-assays) Category: [MRD](https://blog.seracare.com/ngs/tag/mrd), [ccfDNA](https://blog.seracare.com/ngs/tag/ccfdna), [cfDNA](https://blog.seracare.com/ngs/tag/cfdna), [Minimal Residual Disease](https://blog.seracare.com/ngs/tag/minimal-residual-disease), [NGS](https://blog.seracare.com/ngs/tag/ngs), [ctDNA](https://blog.seracare.com/ngs/tag/ctdna), [reference materials](https://blog.seracare.com/ngs/tag/reference-materials) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Aug 17, 2021 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/ctDNA%20MRD%20Blood.jpg)](https://blog.seracare.com/ngs/development-of-a-novel-reference-material-for-mrd-monitoring-assays) Authors: Yves Konigshofer, PhD; Andrew Anfora, PhD; Omo Clement, PhD; and Krystyna Nahlik, PhD. LGC Clinical Diagnostics. Introduction Liquid biopsy methods developed for circulating tumor DNA (ctDNA) analysis in solid tumors are transforming clinical practice, allowing for non-invasive detection and assessment of earlier stages of disease, monitoring for resistance to therapy, and post-treatment monitoring for minimal residual disease (MRD) and recurrence of cancer. The presence of minimal residual disease may be prognostic in that is has been found to correlate with worse patient outcomes, so early and accurate measurement is crucial. ctDNA-based assays allow for the detection of MRD at earlier time points than standard clinical and imaging surveillance, and could allow for treatment modification based on real-time assessment of the tumor genomic landscape. [Read More](https://blog.seracare.com/ngs/development-of-a-novel-reference-material-for-mrd-monitoring-assays) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/development-of-a-novel-reference-material-for-mrd-monitoring-assays#comments-listing) ## [How to resolve the challenges of MRD?](https://blog.seracare.com/ngs/how-to-resolve-the-challenges-of-mrd) Category: [MRD](https://blog.seracare.com/ngs/tag/mrd), [cfDNA](https://blog.seracare.com/ngs/tag/cfdna), [NGS](https://blog.seracare.com/ngs/tag/ngs), [ctDNA](https://blog.seracare.com/ngs/tag/ctdna), [reference materials](https://blog.seracare.com/ngs/tag/reference-materials) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Oct 7, 2020 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/Figure%201%20Yves%20blog%20part2.png)](https://blog.seracare.com/ngs/how-to-resolve-the-challenges-of-mrd) This is part 2 of 2 of the MRD blog post. (Click here for part 1). In this section, we will discuss how to overcome some of the most common challenges of MRD testing. Overcoming the Challenges In order to mitigate sequencing errors, methods using Molecular Barcodes (MBCs), Unique Molecular Identifiers (UMIs), etc. (which are essentially all the same) may be used, where each starting molecule is sequenced many times. The MBCs are then used to generate consensus sequences from sequences that were likely obtained from the same starting molecule. The assumption is that errors appear due to somewhat stochastic processes and that the consensus sequences will likely be correct. This requires many observations of the same starting molecule, so it will be recommended to generate 10-fold more sequences than there are molecules. Therefore, with 8,000 genomic equivalents, we might want to target a sequencing depth of 80,000. This is a reason why using 10-fold more input ccfDNA may not necessarily be a good thing (in addition to having to obtain a 10-fold larger liquid biopsy) since we may have to increase sequencing depth accordingly to 800,000, which could increase the cost of sequencing 10-fold, which could reduce the likelihood for payment and running the assay profitably. [Read More](https://blog.seracare.com/ngs/how-to-resolve-the-challenges-of-mrd) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/how-to-resolve-the-challenges-of-mrd#comments-listing) ## [So, you want to monitor Measurable Residual Disease? What are the challenges?](https://blog.seracare.com/ngs/so-you-want-to-monitor-measurable-residual-disease-what-are-the-challenges) Category: [MRD](https://blog.seracare.com/ngs/tag/mrd), [cfDNA](https://blog.seracare.com/ngs/tag/cfdna), [Minimal Residual Disease](https://blog.seracare.com/ngs/tag/minimal-residual-disease), [NGS](https://blog.seracare.com/ngs/tag/ngs), [ctDNA](https://blog.seracare.com/ngs/tag/ctdna), [reference materials](https://blog.seracare.com/ngs/tag/reference-materials) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Oct 1, 2020 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/Laboratory%20Pipette%20with%20Blue%20Liquid%20Over%20Glass%20Test%20Tubes_.jpeg)](https://blog.seracare.com/ngs/so-you-want-to-monitor-measurable-residual-disease-what-are-the-challenges) Part 1 of 2 Background Measurable Residual Disease (MRD) monitoring – for purposes of this blog – will be the act of looking for somatic variants in a liquid biopsy sample by analyzing circulating cell-free DNA (ccfDNA). This is done to monitor the disappearance of a metastatic solid tumor during treatment and to follow any future reemergence of that cancer. Analyzing ccfDNA assumes that circulating tumor DNA (ctDNA) will be present, and the median ctDNA frequency in patient samples across cancers seems to be around 0.5 to 1 %. Thus, the median variant allele frequencies (VAFs) of the somatic variants will start around this range, and the goal of MRD monitoring is to be able to detect them at much lower VAFs. This can be challenging and if we are going to design an assay for MRD monitoring, then we need to be aware of them and overcome them. [Read More](https://blog.seracare.com/ngs/so-you-want-to-monitor-measurable-residual-disease-what-are-the-challenges) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/so-you-want-to-monitor-measurable-residual-disease-what-are-the-challenges#comments-listing) ## [The Full Authority Companion Diagnostic](https://blog.seracare.com/ngs/the-full-authority-companion-diagnostic) Category: [FDA](https://blog.seracare.com/ngs/tag/fda), [clinical genomics](https://blog.seracare.com/ngs/tag/clinical-genomics), [NGS](https://blog.seracare.com/ngs/tag/ngs) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Feb 21, 2019 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/avian_influenza_flu_bird_pandemic_nature_host_imperial.jpg)](https://blog.seracare.com/ngs/the-full-authority-companion-diagnostic) It is very likely that on your last flight the turbofan engines were controlled by full authority digital engine controls – FADECs for short. FADECs have played a significant role in keeping airline ticket prices low (except during holidays) by continually adjusting engine parameters so that the engine operates with maximum fuel efficiency and within operational limits, allowing pilots to focus on other tasks. [Read More](https://blog.seracare.com/ngs/the-full-authority-companion-diagnostic) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/the-full-authority-companion-diagnostic#comments-listing) ## [Developing a Rock-Solid Lung Cancer Assay, Part 2](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay-part2) Category: [NGS](https://blog.seracare.com/ngs/tag/ngs), [cancer](https://blog.seracare.com/ngs/tag/cancer), [Assay Development](https://blog.seracare.com/ngs/tag/assay-development), [Lung Cancer](https://blog.seracare.com/ngs/tag/lung-cancer) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Jul 2, 2018 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/iStock-902874274.jpg)](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay-part2) In a recent post, we discussed key considerations for designing a robust next-generation sequencing (NGS)-based lung cancer assay. Putting those plans into action in the development phase brings forth a new set of challenges. Through our experience developing NGS reference materials and the relationships we’ve built with assay developers of all stripes, we’ve identified those important factors and ways to navigate them. But before you begin designing and optimizing your assay, you should become very familiar with binomial and Poisson distributions and their use because the outcome of many analytical steps can be modeled and explained with them. [Read More](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay-part2) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay-part2#comments-listing) ## [Developing a Rock-Solid Lung Cancer Assay](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay) Category: [NGS](https://blog.seracare.com/ngs/tag/ngs), [cancer](https://blog.seracare.com/ngs/tag/cancer), [Lung Cancer](https://blog.seracare.com/ngs/tag/lung-cancer), [reference materials](https://blog.seracare.com/ngs/tag/reference-materials) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Mar 15, 2018 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/LungCancer_iStock-837105016.jpg)](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay) Next-generation sequencing (NGS) allows deeper insights than ever before into the human genome and a host of diseases and conditions. So it makes sense that there is a worldwide movement to employ NGS in a growing number of applications. But as the saying goes, with great power comes great responsibility. [Read More](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/developing-a-rock-solid-lung-cancer-assay#comments-listing) ## [Extracting Formalin-fixed, paraffin-embedded (FFPE) nucleic acids for NGS](https://blog.seracare.com/ngs/extracting-formalin-fixed-paraffin-embedded-ffpe-nucleic-acids-for-ngs) Category: [NGS](https://blog.seracare.com/ngs/tag/ngs) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Mar 14, 2017 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/stained_tissue_slide_iStock-150678562.jpg)](https://blog.seracare.com/ngs/extracting-formalin-fixed-paraffin-embedded-ffpe-nucleic-acids-for-ngs) In the course of patient care, formalin-fixation and paraffin-embedding (FFPE) of biopsy tissue samples are routinely performed, where these samples can be analyzed by histology and archived to link the sample with clinical long-term follow-up. With the development of advanced NGS-based oncology gene panels, it is becoming increasingly important to consider pre-analytic variables when extracting nucleic acids from FFPE-treated samples. This post covers frequently asked questions (FAQs) around the extraction of nucleic acids from FFPE samples for downstream NGS analysis. [Read More](https://blog.seracare.com/ngs/extracting-formalin-fixed-paraffin-embedded-ffpe-nucleic-acids-for-ngs) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/extracting-formalin-fixed-paraffin-embedded-ffpe-nucleic-acids-for-ngs#comments-listing) ## [FDA-AACR Liquid Biopsies in Oncology Drug and Device Workshop](https://blog.seracare.com/ngs/fda-aacr-liquid-biopsies-in-oncology-drug-and-device-workshop) Category: [FDA](https://blog.seracare.com/ngs/tag/fda), [clinical genomics](https://blog.seracare.com/ngs/tag/clinical-genomics), [NGS](https://blog.seracare.com/ngs/tag/ngs), [cancer](https://blog.seracare.com/ngs/tag/cancer), [LDT](https://blog.seracare.com/ngs/tag/ldt), [ctDNA](https://blog.seracare.com/ngs/tag/ctdna), [reference materials](https://blog.seracare.com/ngs/tag/reference-materials) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Aug 8, 2016 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/Poisson_Figure_2.png)](https://blog.seracare.com/ngs/fda-aacr-liquid-biopsies-in-oncology-drug-and-device-workshop) The presentations during the FDA-AACR Liquid Biopsies in Oncology Drug and Device Development Workshop on July 19, 2016 included several important pieces of information that will likely guide the development of assays and their review by the FDA. [Read More](https://blog.seracare.com/ngs/fda-aacr-liquid-biopsies-in-oncology-drug-and-device-workshop) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/fda-aacr-liquid-biopsies-in-oncology-drug-and-device-workshop#comments-listing) ## [The FDA NGS-based Oncology Panels Workshop](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/38/the-fda-ngs-based-oncology-panels-workshop.aspx) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Apr 1, 2016 12:00:00 AM [![](https://blog.seracare.com/hubfs/Imported_Blog_Media/FDA_logo.jpg)](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/38/the-fda-ngs-based-oncology-panels-workshop.aspx) The U.S. Food and Drug Administration on February 25, 2016 held an all-day public workshop entitled “Next Generation Sequencing-based Oncology Panels” at their White Oak campus in Silver Spring, Maryland. Companion diagnostics were a recurring theme of the initial FDA presentations at this Next Generation Sequencing-Based Oncology Panels Workshop and these important tests will be our focus here. The slides that were presented at the workshop are available (PDF) and are referenced below, and those presented by SeraCare’s CSO Russell Garlick start on page 196. [Read More](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/38/the-fda-ngs-based-oncology-panels-workshop.aspx) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/38/the-fda-ngs-based-oncology-panels-workshop.aspx#comments-listing) ## [Does synthetic DNA sequence behave the same as cell-line DNA?](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/32/does-synthetic-dna-sequence-behave-the-same-as-cell-line-dna.aspx) Posted by [Yves Konigshofer, PhD](https://blog.seracare.com/ngs/author/yves-konigshofer-phd) on Feb 5, 2016 12:00:00 AM A recurring question SeraCare has been asked is whether synthetic DNA sequences perform similarly to cell line-derived sequences. For example, it could be hypothesized that secondary structure and/or the GC content of the DNA around a particular amplicon might lead to a detection bias when only 400 bases on either side of the amplicon are present compared to when many kilobases are present. [Read More](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/32/does-synthetic-dna-sequence-behave-the-same-as-cell-line-dna.aspx) 0 Comments [Click here to read/write comments](https://blog.seracare.com/ngs/home/tabid/294/artmid/989/articleid/32/does-synthetic-dna-sequence-behave-the-same-as-cell-line-dna.aspx#comments-listing) [All posts](https://blog.seracare.com/ngs/all) [Next](https://blog.seracare.com/ngs/author/yves-konigshofer-phd/page/2) ### Subscribe Here!   ### Posts by Tag - [NGS (64)](https://blog.seracare.com/ngs/tag/ngs) - [reference materials (37)](https://blog.seracare.com/ngs/tag/reference-materials) - [clinical genomics (30)](https://blog.seracare.com/ngs/tag/clinical-genomics) - [ctDNA (29)](https://blog.seracare.com/ngs/tag/ctdna) - [cancer (24)](https://blog.seracare.com/ngs/tag/cancer) - [SeraSeq (16)](https://blog.seracare.com/ngs/tag/seraseq) - [cfDNA (14)](https://blog.seracare.com/ngs/tag/cfdna) - [NIPT (12)](https://blog.seracare.com/ngs/tag/nipt) - [RNA fusion (11)](https://blog.seracare.com/ngs/tag/rna-fusion) - [AACR (10)](https://blog.seracare.com/ngs/tag/aacr) - [AMP (10)](https://blog.seracare.com/ngs/tag/amp) - [liquid biopsy (10)](https://blog.seracare.com/ngs/tag/liquid-biopsy) - [FDA (7)](https://blog.seracare.com/ngs/tag/fda) - [ccfDNA (7)](https://blog.seracare.com/ngs/tag/ccfdna) - [LDT (6)](https://blog.seracare.com/ngs/tag/ldt) - [Assay Development (5)](https://blog.seracare.com/ngs/tag/assay-development) - [Reproductive Health (5)](https://blog.seracare.com/ngs/tag/reproductive-health) - [Accuplex (4)](https://blog.seracare.com/ngs/tag/accuplex) - [NTRK (4)](https://blog.seracare.com/ngs/tag/ntrk) - [Non-invasive Prenatal Testing (4)](https://blog.seracare.com/ngs/tag/non-invasive-prenatal-testing) - [QC Challenges (4)](https://blog.seracare.com/ngs/tag/qc-challenges) - [qc management (4)](https://blog.seracare.com/ngs/tag/qc-management) - [Lung Cancer (3)](https://blog.seracare.com/ngs/tag/lung-cancer) - [MRD (3)](https://blog.seracare.com/ngs/tag/mrd) - [New Reference Material (3)](https://blog.seracare.com/ngs/tag/new-reference-material) - [#Quality (2)](https://blog.seracare.com/ngs/tag/quality) - [EGFR (2)](https://blog.seracare.com/ngs/tag/egfr) - [Inherited Disease (2)](https://blog.seracare.com/ngs/tag/inherited-disease) - [Methylated DNA (2)](https://blog.seracare.com/ngs/tag/methylated-dna) - [Minimal Residual Disease (2)](https://blog.seracare.com/ngs/tag/minimal-residual-disease) - [Molecular Pathology (2)](https://blog.seracare.com/ngs/tag/molecular-pathology) - [PGT (2)](https://blog.seracare.com/ngs/tag/pgt) - [QC Management Software (2)](https://blog.seracare.com/ngs/tag/qc-management-software) - [TMB (2)](https://blog.seracare.com/ngs/tag/tmb) - [Women's health (2)](https://blog.seracare.com/ngs/tag/womens-health) - [myeloid cancer reference materials (2)](https://blog.seracare.com/ngs/tag/myeloid-cancer-reference-materials) - [ngs validation (2)](https://blog.seracare.com/ngs/tag/ngs-validation) - [trisomy (2)](https://blog.seracare.com/ngs/tag/trisomy) - [zika virus (2)](https://blog.seracare.com/ngs/tag/zika-virus) - [BioFidelity (1)](https://blog.seracare.com/ngs/tag/biofidelity) - [Breast Cancer (1)](https://blog.seracare.com/ngs/tag/breast-cancer) - [COVID-19 (1)](https://blog.seracare.com/ngs/tag/covid-19) - [Customer Testimonial (1)](https://blog.seracare.com/ngs/tag/customer-testimonial) - [Genomic Testing (1)](https://blog.seracare.com/ngs/tag/genomic-testing) - [HIV (1)](https://blog.seracare.com/ngs/tag/hiv) - [Immuno-Oncology (1)](https://blog.seracare.com/ngs/tag/immuno-oncology) - [PGS (1)](https://blog.seracare.com/ngs/tag/pgs) - [PGT-A (1)](https://blog.seracare.com/ngs/tag/pgt-a) - [Preimplantation genetic testing (1)](https://blog.seracare.com/ngs/tag/preimplantation-genetic-testing) - [QC Reporting (1)](https://blog.seracare.com/ngs/tag/qc-reporting) - [QC data management (1)](https://blog.seracare.com/ngs/tag/qc-data-management) - [Quality Management Systems (1)](https://blog.seracare.com/ngs/tag/quality-management-systems) - [SARS-CoV-2 (1)](https://blog.seracare.com/ngs/tag/sars-cov-2) - [bioinformatics (1)](https://blog.seracare.com/ngs/tag/bioinformatics) - [laboratory training (1)](https://blog.seracare.com/ngs/tag/laboratory-training) - [listeria (1)](https://blog.seracare.com/ngs/tag/listeria) - [methylated (1)](https://blog.seracare.com/ngs/tag/methylated) See all ### Recent Posts **About SeraCare** With over 30 years of experience as a leading partner to global in vitro diagnostics manufacturers and clinical testing laboratories, SeraCare’s clinical genomics technologies enable the promise of precision medicine by helping scientists and clinicians build and implement better clinical genomics assays. [Learn More](http://www.seracare.com/Company/WhoWeAre/tabid/335/Default.aspx)    - - - [Privacy Policy](http://www.seracare.com/PrivacyPolicy/tabid/211/Default.aspx)  |  [Legal Statement ](http://www.seracare.com/LegalStatement/tabid/212/Default.aspx) **Learn More** [Home](http://seracare.com/)  [About Us](http://seracare.com/Company/WhoWeAre/tabid/335/Default.aspx) [News and Events](http://www.seracare.com/NewsEvents/NewsCenter/tabid/354/Default.aspx)  [Blog](https://blog.seracare.com/)  [Contact](http://seracare.com/Contact/tabid/366/Default.aspx)  ![LGC+Marine-logo-FINAL-teal](https://blog.seracare.com/hs-fs/hubfs/1.%20Logos/LGC+Marine-logo-FINAL-teal.png?width=150&name=LGC+Marine-logo-FINAL-teal.png) 37 Birch Street Milford, MA 01757 [508-244-6400](tel:508-244-6400) l [800-676-1881](tel:800-676-1881) [info@seracare.com](mailto:info@seracare.com) ©2017 SeraCare Life Sciences, Inc. - [About SeraCare](http://www.seracare.com/Company/WhoWeAre/tabid/335/Default.aspx) - [Learn More](http://seracare.com/) - 37 Birch Street Milford, MA 01757 - Google Maps - 508-244-6400 - 508-634-3334 Fax - - - ![logo](https://blog.seracare.com/hubfs/logo.png "logo") 37 Birch Street Milford, MA 01757 508-244-6400 508-634-3334 Fax #### Products #### SeraCare #### Support & Resources - NGS & Digital PCR Tools - Controls & Reference Materials - Validation & Qualification Materials - Plasma & Serum Diluents & Derivatives - Cell Culture Reagents - KPL Antibodies & Conjugates - KPL Immunoassay Reagents & Kits - About Us - Careers - Press Releases - News Articles - Quality Systems - Terms & Conditions - Privacy Policy & Legal Statement - Register for an Account - Contact Us - Sign In - Resource Library - FAQs - Scientific Posters - White Papers - Videos