MAQC Society – SEQC2 Webinar Series
It is an FDA‐led community wide consortium effort to address issues relating to the application of constantly evolving high‐throughput genomics technologies to either assess safety and efficacy of FDA regulated products or their safe and effective use in clinical applications as in vitro diagnostic devices. The MAQC consortium completed three projects between 2005 ‐2014 (namely MAQC I, II and III), resulting in ~30 publication. The fourth phase of efforts are captured under the initiative of Sequencing Quality Control (SEQC2) which will be covered in this webinar series. Shortly, previous webinars will be available to all MAQC Society members.
Previous Webinars and Video Recordings
Tuesday, February 16th, 2021
A MAQC/SEQC Journey Towards Reproducible Genomics and the MAQC Society
Weida Tong, PhD
President, MCBIOS, and Director, Division of Bioinformatics and Biostatistics, FDA-NCTR
Wendell Jones, PhD
Executive Chair and President, MAQC Society, and Principal Bioinformaticist and Scientific Advisor, Q2 Solutions / EA Genomics
Dr. Wenming Xiao
Senior Scientific Reviewer, Division of Molecular Genetics and Pathology, FDA-OIR
Tuesday, February 23, 2021
Towards Best Practice in Cancer Mutation Detection with Whole-genome and Whole-exome Sequencing
Here we systematically interrogated somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy. Different types of samples with varying input amount and tumor purity were processed using multiple library construction protocols. Whole-genome (WGS) and whole-exome sequencing (WES) were carried out at six sequencing centers followed by processing with nine bioinformatics pipelines to evaluate reproducibility. We identified artifacts of C>A mutations in WES due to sample and library processing and highlighted limitations of bioinformatics tools for artifact detection and removal.
Dr. Xiao had advanced training in biology and computer science in China and United States. He has numerous publications in peer-reviewed journals such as Nature, PNAS, and N. Engl. J. Med and received NIH Director Award in 2010 in recognition to his contributions to cancer biomarkers discovery. Dr Xiao was a principle investigator in FDA and led an international working group to establish reference materials, data sets, analysis pipelines, and quality metrics for cancer mutation detection with NGS technology. Currently, Dr. Xiao is a lead reviewer for NGS related diagnosis products/applications (510k, IDE or PMA), including: Onco-Panel, Whole-Exome Panel, NIPT, Gene Expression Signature, and analytical software (bioinformatics pipelines, knowledge databases), and provides recommendation on regulatory decisions regarding the safety and effectiveness of medical devices.
March 2, 2021, 11:00 am - 12:00 Noon ET
Establishing Reference Data and Call Sets for Benchmarking Cancer Mutation Detection using Whole-genome Sequencing
Dr. Li Tai Fang is currently a Staff Scientist at Endpoint Health, Inc. He worked on the SEQC2’s somatic reference project when he was at Roche Sequencing Solutions. Previously at Bina Technologies Inc., he led Bina Team’s participation in the ICGC-TCGA DREAM Somatic Mutation Calling Challenge (#1 and #2 in Stage 5 indel and SNV sub-challenges), and developed software such as SomaticSeq.
Li Tai Fang, PhD
Staff Scientist, Endpoint Health, Inc.
Charles Wang, MD, PhD, MPH
Professor and Director of Center for Genomics, Loma Linda University School of Medicine
Tuesday, March 9, 2021 11:00 am - 12:00 Noon ET
A Multicenter Study Benchmarking Single-cell RNA Sequencing Technologies using Reference Samples
Companion single-cell Scientific Data paper: https://www.nature.com/articles/s41597-021-00809-x
Charles Wang, MD, PhD, MPH is Director of the Center for Genomics and a tenured full Professor at the Loma Linda University School of Medicine. He had held the positions as Clinical Transcriptional Genomics Core Director at Cedars-Sinai Medical Center, Associate Professor of Medicine at the David Geffen School of Medicine at UCLA and Director of the Functional Genomics Core at City of Hope. Dr. Wang is a well-recognized expert in genomics, with many high visibility publications published in prestigious journals including Nature Biotechnology, Nature Communications and PNAS. He was one of the pioneers for the MAQC- and SEQC-consortium projects.
Tuesday, March 16, 2021 11:00 am - 12:00 Noon ET
Critical Assessment of Copy Number Variation Calling Using Next Generation Sequencing
Dr. Pirooznia is also an Adjunct Associate Professor at the Johns Hopkins University School of Medicine, where he served for 8 years as a faculty prior to joining the NIH in 2016, and provided leadership, scientific direction and was responsible for implementing the high-performance computational laboratory and bioinformatics system. Dr. Pirooznia serves as an editor and reviewer for several scientific journals such as Bioinformatics, Nature Scientific Data, BMC Bioinformatics, and Human Genomics. He is also a member of The American Society of Human Genetics (ASHG), and the International Society for Computational Biology (ISCB).
Mehdi Pirooznia , MD, MSc, PhD
Director of Bioinformatics and Computational Biology Core, NHLBI
Wendell Jones, PhD
Principal Bioinformaticist and Scientific Advisor, Q2 Solutions / EA Genomics - Executive Chair and President, MAQC Society
March 23, 2021, 11:00 am - 12:00 Noon ET
A Verified Genomic Reference Sample for Assessing Performance of Cancer Panels Detecting Small Variants of Low Allele Frequency
March 30, 2021, 11:00 am - 12:00 Noon ET
Multi-lab Cross-oncopanel Study Reveals High Sensitivity and Reproducibility Tailored to Targeted Regions and Allele Frequency Ranges
Best practices for oncopanel sequencing, a tool in cancer diagnosis and treatment, requires comprehensive assessments of reproducibility and detection sensitivity. By employing reference materials characterized by the FDA-led SEQC project phase2 (SEQC2), we performed a cross-platform multi-lab evaluation of eight Pan-Cancer panels representing a broad spectrum of oncopanel technologies. The study reveals consistently high sensitivity across targeted high confidence coding regions, variant types (SNVs vs small indels or MNVs) for the variant allele frequency (VAF) above 5%. Sensitivity was reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Conversely, enforcing a VAF threshold for reporting had a positive impact on reducing false positive (FP) calls. All panels have low FP rates of approximately 1 FP per Mb or less for VAF greater than 5% in the high confidence coding regions, and thus led to good reproducibility. Importantly, the FP rate was found to be noticeably and significantly higher outside the high confidence coding regions, resulting in lower reproducibility. Region restriction and VAF thresholds led to low relative technical variability in estimating the promising biomarkers such as tumor mutational burden. This study details actionable insights into factors underpinning the sensitivity and reproducibility of oncopanel sequencing.
Binsheng Gong, PhD
Staff Fellow, Division of Bioinformatics and Biostatistics, FDA-NCTR
Joshua Xu, PhD
Branch Chief for Research-to-Review — Division of Bioinformatics and Biostatistics, FDA-NCTR and Executive Secretary, MAQC Society
April 6, 2021, 11:00 am - 12:00 Noon ET
Evaluating the Analytical Validity of Circulating Tumor DNA Sequencing for Precision Oncology
April 7, 2021, 11:00 am - 12:00 Noon ET
Robust Cancer Mutation Detection with Deep Learning Models Derived from Tumor-Normal Sequencing Data
Mohammad Sahraeian, PhD
Senior Bioinformatics Scientist, Roche Sequencing Solutions
Christopher Mason, PhD
Associate Professor; Director, WorldQuant Initiative for Quantitative Prediction Physiology and Biophysics/Feil Family Brain and Mind Institute/Institute for Computational Biomedicine, Weill Cornell Medicine
April 13, 2021, 11:00 am - 12:00 Noon ET
The Epigenome Quality Control (EpiQC) Project
April 14, 2021, 11:00 am - 12:00 Noon ET
Multi-Platform Assessment of DNA Sequencing Performance using Human and Bacterial Reference Genomes in the ABRF Next-Generation Sequencing Study
With a background in evolutionary biology, I researched for my PhD the phylogenomics of Myxozoa, a group of bizarre, microscopic endoparasites of economically critical fish (among other hosts) around the world. I explored the genomic underpinnings of how myxozoans, whose closest living relatives are medusozoans (jellyfish, hydras, cube jellies), became so radically different in biology, ecology, and life history.
Jonathan Foox, PhD
Research Associate in Computational Biomedicine, Weill Cornell Medicine
Huixiao Hong, PhD
Chief, Bioinformatics Branch, FDA-NCTR