Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE) Webinar Series
The Epidemiology and Genomics Research Program hosts a webinar series entitled "Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE)." The purpose of this forum is to provide an opportunity for our grantees and other interested individuals to share lessons learned and practical information regarding the application of next generation sequencing to cancer epidemiology studies.
By sharing lessons learned across funded projects, EGRP aims to facilitate higher quality research and more interpretable genetic research studies for the future. In addition, the webinar participants may work together to establish best practices for epidemiology research.
Any interested individual is invited to participate, however pre-registration is required. Each presentation will be about 30 minutes in length and allow for 30 minutes of discussion. Instructions for connecting to the webinars will be sent via e-mail to individuals who register for the webinars.
The past decade has seen a transformation in genetic epidemiology of complex diseases, from linkage to association studies, which progressed from investigating single variants in candidate genes, to genome-wide approaches, including genome-wide association studies (GWAS). GWAS have successfully identified hundreds of common genetic variants associated with cancer and other complex diseases, however with the advent of next-generation parallel DNA sequencing technologies, there is a renewed interest in examining the role of rare variants and other forms of genetic variation in complex disease etiology. While sequencing of thousands of cancer-normal genomes is estimated to be completed worldwide by the end of 2014, germline sequencing in epidemiologic studies of cancer risk are relatively nascent.
Sequencing technology is more technically difficult than genotyping using GWAS arrays and requires unique considerations related to the study design and techniques used for sequencing and analysis. Quality control standards are needed for sequencing across samples, platforms, and institutions. GWAS arrays had high reproducibility and concordance, but this is not yet the case for sequencing data. In addition, combining data from different studies is more challenging in sequencing studies than GWAS. Poorly designed studies will result in uninterpretable or even biased results.
Upcoming Topics and Speakers
Predisposition Genes and Breast Cancer Risk in African American Women
3:00 p.m. to 4:00 p.m. ET
Dr. Julie Palmer is a cancer epidemiologist based at the Slone Epidemiology Center, with research projects spanning cancer early detection, etiology, and survivorship. Her primary focus is on elucidating reasons for the disproportionately high incidence of hormone receptor negative breast cancer in African American women and on understanding and reducing racial disparities in breast cancer mortality. She is a founding leader of the Black Women’s Health Study (BWHS), a prospective cohort study of 59,000 African American women who enrolled in 1995 and have been followed by biennial questionnaire since that time. Her breast cancer research within the BWHS includes work on risk prediction models for breast cancer in African American women, identifying differences in childbearing patterns as a contributing cause to the excess incidence of estrogen receptor negative breast cancer in African American women, and investigating the interrelationships of type 2 diabetes, obesity, and inflammation on breast cancer risk. In this webinar, Dr. Palmer will be presenting on predisposition genes and breast cancer risk in African American women.
GWAS of Persistent High-Risk HPV Infection: Results from an H3Africa Collaborative Center
3:00 p.m. to 4:00 p.m. ET
Dr. Clement Adebamowo is a Professor of Epidemiology and Public Health as well as the Director of Global Health Research at the University of Maryland School of Medicine. He is also the Principal Investigator (PI) of the NIH-funded African Collaborative Center for Microbiome and Genomics Research (ACCME) which is one of the NIH/Wellcome Trust funded Human Heredity and Health in Africa (H3Africa) initiative on genomics research and education in Africa. In addition, he is the PI for the NIH-funded Training Program in Non-Communicable Diseases Research in Nigeria (Traping-NCD) that has trained 12 advanced degrees and post-doctoral trainees to date. In this webinar, Dr. Adebamowo will be presenting on genomic results from an H3Africa collaborative center.
Unbiased Identification of Spliceosome Vulnerabilities Across Cancer
3:00 p.m. to 4:00 p.m. ET
Dr. Nathan Salomonis is an Assistant Professor in the UC Department of Biomedical Informatics at the Cincinnati Children’s Hospital Medical Center. His research group at the Salomonis Lab is working to understand the role of alternative splicing in human development and disease and integrate these results with epigenetic, gene expression, proteomic, and single-cell sequencing data. They also develop new computational methods for analyzing data generated by emerging sequencing technologies. In this webinar, Dr. Salomonis will be presenting on unbiased identification of spliceosome vulnerabilities across cancer.
Somatic Mutations in High Grade Endometrial Cancers
3:00 p.m. to 4:00 p.m. ET
Dr. Michele Cote is a Professor of Oncology at the Wayne State University School of Medicine and the Associate Center Director for Education at the Karmanos Cancer Institute. The focus of Dr. Cote’s research is the intersection of molecular epidemiology and health disparities. Specifically, she is interested in examining genetic and molecular factors in lung and female cancers that impact disease occurrence or prognosis in underserved populations. Highlights of her previous work include the first report in African Americans of increased risk of lung cancer associated with familial aggregation of lung cancer, and assessment of somatic mutations in endometrial tumors from African American women. In this webinar, Dr. Cote will be presenting on somatic mutations in high grade endometrial cancers.
Lessons Learned Sequencing in Familial Glioma
3:00 p.m. to 4:00 p.m. ET
Dr. Melissa Bondy is Chair of the Department of Epidemiology and Population Health at Stanford University, and Dr. Matthew Bainbridge is CEO of Codified Genomics and Associate Director of Clinical Genomics Research at Rady Children’s Hospital’s Genomic Institute. At the Bondy Lab, Drs. Bondy (Director) and Bainbridge (Co-Investigator) head up Gliogene, the largest genetic study of glioma in families which aims to learn more about the heritable genes that may contribute to brain tumors. In this webinar, Drs. Bondy and Bainbridge will be presenting on lessons learned sequencing in familial glioma.
Lessons Learned from GenoMEL’s Next Generation Sequencing Cloud Project
3:00 p.m. to 4:00 p.m. ET
Dr. Alisa Goldstein is a Senior Investigator in NIH’s Division of Cancer Epidemiology and Genetics (DCEG), Clinical Genetics Branch. Her research focuses on genetic epidemiologic studies of several cancers, including melanoma and upper gastrointestinal (UGI) cancer. The main goal of her studies is to understand the role of genetic and environmental factors in the etiology of these cancers. Her studies combine epidemiologic, genetic, clinical, and molecular methodologies. Dr. Goldstein is one of the leads of the Melanoma Genetics Consortium (GenoMEL). In this webinar, Dr. Goldstein will be presenting on lessons learned from GenoMEL’s Next Generation Sequencing cloud project.
Genetics, Genomics and Precision Medicine of Gastric Cancer in Latinos
3:00 p.m. to 4:00 p.m. ET
Dr. Luis Carvajal-Carmona is Professor and Auburn Community Cancer Endowed Chair in Basic Science in the Department of Biochemistry and Molecular Medicine at UC Davis Health School of Medicine. He also is the leader of the Cancer Center’s Latinos United for Cancer Health Advancement (LUCHA) initiative and the co-director Community Engagement Program at the Clinical and Translational Science Center. His research group at the Carvajal-Carmona Lab is interested in the study of cancer genetic susceptibility. They use genetic, genomic, and functional approaches to identify novel cancer-causing gene and mutations in human populations, to investigate the function of genetic variation associated with disease, and to carry out pre-clinical studies aimed at developing better molecularly guided therapies. In this webinar, Dr. Carvajal-Carmona will be presenting on genetics, genomics, and precision medicine of gastric cancer in Latinos.
Past Topics and Speakers
Next Generation Sequencing and Tumor Initiation and Progression
3:00 p.m. to 4:00 p.m. ET
Dr. Christina Curtis is an Associate Professor in the Departments of Medicine (Oncology) and Genetics in the School of Medicine at Stanford University where she leads the Cancer Computational and Systems Biology Group and is Co-Director of the Molecular Tumor Board at the Stanford Cancer Institute. The Curtis laboratory is focused on the development and application of innovative experimental, computational, and analytical approaches to improve the diagnosis, treatment, and early detection of cancer. Dr. Curtis presented on next generation sequencing and tumor initiation and progression.
Polygenic Risk Scores: Development, Validation and Applications
3:00 p.m. to 4:00 p.m. ET
Nilanjan Chatterjee, Ph.D.
Bloomberg Distinguished Professor
Professor, Biostatistics, Johns Hopkins School of Public Health
Professor, School of Medicine, Johns Hopkins University
Professor, Epidemiology, Johns Hopkins School of Public Health
Dr. Chatterjee leads a broad research program in quantitative research that cuts across multiple areas of modern population-based biomedical science including statistical genetics/genomics, precision medicine and big data. The scientific goals of his studies include discovery of new biomarkers, understanding disease mechanisms, characterizing disease risk and developing risk-stratified approaches to disease prevention. In this webinar, Dr. Chatterjee presented research on polygenic risk scores.
Leveraging Cross-Cancer Shared Heritability to Better Understand the Genetic Architecture of Cancer
3:00 p.m. to 4:00 p.m. ET
Dr. Sara Lindstroem is an Assistant Professor of Epidemiology at the University of Washington School of Public Health in Seattle, WA. Dr. Lindstroem’s research focuses on understanding the genetic contribution to common complex diseases, with a primary emphasis on cancer and linked traits. By leveraging long-running large population-based studies, she investigates how our genetics and environment affect our risk of developing disease. Current research projects include studying the shared genetic origin between common cancers and the genetics underlying childhood obesity, breast tissue composition and venous thromboembolism. Dr. Lindstroem is also interested in finding approaches to incorporate information about the functional characteristics of the genome in my studies. Dr. Lindstroem presented on leveraging cross-cancer shared heritability to better understand the genetic architecture of cancer.
Sequencing in Diverse Populations
3:00 p.m. to 4:00 p.m. ET
Dr. Eimear Kenny is Founding Director of the Center for Genomic Health, and Associate Professor of Medicine and Genetics and Genomic Sciences as well as the Icahn Institute for Data Science and Genomic Technology at Mount Sinai. She is a statistical and population geneticist by training. She leads a multi-disciplinary team focused on solving problems at the interface of genetics, ancestry and medicine. She is a scientific advisor to many genomic medicine initiatives in government, non-profit and industry arenas. Dr. Kenny presented on sequencing in diverse populations.
Methods of Functional Annotation of Genetic Variants
3:00 p.m. to 4:30 p.m. ET
Frederick Roth, Ph.D.
Canada Excellence Research Chair in Integrative Biology, Department of Molecular Genetics, University of Toronto
Professor, Department of Computer Science, University of Toronto
Senior Scientist, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto
Rachel Karchin, Ph.D.
The William R. Brody Faculty Scholar Institute for Computational Medicine, School of Engineering, Johns Hopkins University
Professor, Oncology and Computer Science, Johns Hopkins University
In this webinar, the panelists each presented on methods of functional annotation of genetic variants.
Dr. Frederick (Fritz) Roth is the Canada Excellence Research Chair in Integrative Biology at the University of Toronto. He studies designs and interprets large-scale genetic and biochemical experiments to understand pathway structure and its relationship to phenotype and human disease, with a strong emphasis on protein interaction mapping, genetic interaction mapping, and identifying causal genes and variants in human disease.
Dr. Rachel Karchin is the William R. Brody Faculty Scholar for the Whiting School of Engineering from 2013 to 2019 at Johns Hopkins University. Dr. Karchin is a leading translational computational biologist. She develops novel algorithms and software to analyze genomic data and interpret its impact on cancer, the immune system, and tumor evolution. As a core member of the Johns Hopkins University Institute for Computational Medicine, Dr. Karchin has created leading-edge tools to interpret genomic variants, identify cancer drivers, and model multivariate biomarkers of cancer prognosis and of tumor evolution.
Dr. Jinghui Zhang is the Chair of Department of Computational Biology and the St. Jude Endowed Chair in Bioinformatics at St. Jude’s Research Hospital. Dr. Zhang is a computational biologist focused on the integrative analysis of large-scale, multi-dimensional genomic data to understand the initiation and progression of diseases. Her research interest has been in the development of highly accurate and sensitive computational methods for analyzing large-scale genomic data, especially in the area of detecting and analyzing genetic variations and somatic mutations.
Research Identifying Germline Predisposition Variants in Sequencing Studies
3:00 p.m. to 4:00 p.m. ET
Ms. Fernanda Martins Rodrigues is a Ph.D. student in Molecular Genetics at Washington University in Saint Louis working with Dr. Li Ding at the Ding Lab. The goal of her research is to use computational tools to better understand cancer genetics. In this webinar, Ms. Martins Rodrigues presented on research identifying germline predisposition variants in sequencing studies.
Lessons Learned Sequencing Precancerous Lesions
3:00 p.m. to 4:00 p.m. ET
Dr. Jennifer Beane's research interests include smoking effects on airway epithelial gene expression; gene expression-based diagnostic for lung cancer; and lung cancer chemoprevention and understanding biology associated with the development of lung squamous premalignant lesions. In this webinar, Dr. Beane presented on lessons learned sequencing precancerous lesions.
Strategies for Sequencing the Microbiome
3:00 p.m. to 4:00 p.m. ET
Andrew T. Chan, M.D., M.P.H.
Professor, Medicine, Harvard Medical School
Vice Chair, Education, Gastroenterology, Massachusetts General Hospital
Chief, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital
Dr. Andrew Chan’s overall mission is to advance epidemiologic investigation for the translation of discoveries into effective clinical interventions. He currently focuses on chronic digestive diseases, including gastrointestinal cancer (colorectal, esophageal, pancreatic), inflammatory bowel disease, diverticulitis, and gastrointestinal bleeding. He utilizes molecular approaches encompassing genetic, metabolomic, proteomic, and biochemical platforms applied to populations ranging from large cohort studies to small biomarker-driven clinical trials. He also investigates the oral and gut microbiome as a determinant and mediator of chronic disease. Dr. Chan presented on strategies for sequencing the microbiome.
Practical Considerations for Genomic Sequencing Studies in a Low Resource Setting
3:00 p.m. to 4:30 p.m. ET
Dr. Timothy Rebbeck is a Vincent L. Gregory, Jr. Professor of Cancer Prevention and Epidemiology at the Harvard T.H. Chan School of Public Health as well as a Professor of Medical Oncology at the Dana-Farber Cancer Institute. He leads molecular epidemiology studies of cancer etiology, outcomes, health disparities, and global health. His work has led to an understanding of the genetic and environmental causes of breast, prostate, skin, endometrial and ovarian cancers. He founded and lead international cancer consortia that study risk and outcomes of 1) cancer in BRCA1/BRCA2 mutation carriers, and 2) prostate cancer in men of African descent in North America, the Caribbean, and Africa. Dr. Rebbeck presented on practical considerations for genomic sequencing studies in a low resource setting.
Sequencing in the CARRIERS Consortium and Other Lessons Learned from Cancer Predisposition Gene Sequencing Studies
3:00 p.m. to 4:30 p.m. ET
Dr. Fergus Couch is a Zbigniew and Anna M. Scheller Professor of Medical Research and Chair of the Division of Experimental Pathology and Laboratory Medicine at the Mayo Clinic in Rochester, MN. He studies how genetic alterations influence the development of both breast and pancreatic cancer. The long-term goals of his research program are to develop methods that predict an individual's risk of developing breast cancer and facilitate cancer prevention efforts, as well as develop tests that improve selection of treatment for individuals with breast and pancreatic cancer. In this webinar, Dr. Couch presented on sequencing in the CARRIERS consortium and other lessons learned from cancer predisposition gene sequencing studies.
Sequencing Studies of Germline Variation in Prostate Cancer
Dr. Nicholas Mancuso is currently a post-doctoral researcher in computational/statistical genetics in Dr. Bogdan Pasaniuc’s laboratory at University of California, Los Angeles (UCLA). His research interests include developing novel computational and statistical methods to identify genetic risk factors for prostate cancer using low-coverage sequencing data, rare genetic variation, and gene expression variation in large studies. Dr. Mancuso presented on whole genome sequencing study of prostate cancer.
Dr. Christopher Haiman is an Associate Professor of Preventive Medicine in the Zilkha Neurogenetic Institute at University of Southern California (USC) Keck School of Medicine. His major research focus is in the genetic basis of cancer in minority populations. He has led several large genetic studies on the prostate, including the African Ancestry Prostate Cancer GWAS Consortium (AAPC, PI) and the ELLIPSE U19 GAME-ON project (co-PI). Dr. Haiman presented on a sequencing study of aggressive prostate cancer.
A Single Cell Atlas of Mammalian Chromatin
Dr. Jay Shendure is a Professor in the Department of Genome Sciences at the University of Washington School of Medicine and an Affiliate Investigator in the Human Biology Division at the Fred Hutchinson Cancer Research Center. Dr. Shendure’s research is focused on developing and applying new technologies in genomics. In 2005, his doctoral research with George M. Church resulted one of the first successful proof-of-concepts of next-generation DNA sequencing. His research group at the University of Washington pioneered exome sequencing and its application to Mendelian disorders, a strategy that has been applied to identify hundreds of disease-causing genes. Dr. Shendure presented on lessons learned and insights from application of single cell sequencing.
Developing dbGaP Access for Read Data Stored in Google and Amazon using Fusera
Stephen Sherry, Ph.D.
Head, Sequence Enhancements Program, National Center for Biotechnology Information (NCBI)
Chief, Reference Collections Section, Information Engineering Branch, NCBI
Dr. Stephen Sherry is Head of the Sequence Enhancements Program and Chief of the Reference Collections Section (Information Engineering Branch) at the National Center for Biotechnology Information (NCBI) in Bethesda, MD. His research focuses on the architecture of population genetic information and how it relates to modern notions of privacy. Dr. Sherry presented on the development dbGaP access for read data stored in Google and Amazon using Fusera.
Analytical Methods for Next Generation Sequencing Data
Dr. Kathryn Roeder is a Professor of Statistics and Computational Biology and Vice Provost for Faculty at Carnegie Mellon University. The primary goal of Dr. Roeder's research focuses on using statistical tools to find associations between patterns of genetic variation and complex disease. Dr. Roeder presented on analytical methods for next generation sequencing data.
Lessons Learned from the Broad Sequencing Center
Dr. Stacey Gabriel is the Senior Director of the Genomics Platform at the Broad Institute of MIT and Harvard and an Institute Scientist at the Broad Institute. Under Dr. Gabriel's guidance, the Genomics Platform operates as one of the largest sequencing centers in the world and continually explores, validates, optimizes, and implements new technologies, methods, and analysis tools to meet the needs of the Broad community. In addition to her activities with the Genomics Platform, her research interests lie in using genomic techniques to understand the genetic basis of common diseases. Dr. Gabriel presented on lessons learned from the Broad sequencing center.
The Relation Between Germline Genetic Variations and Tumor Development
Dr. Hannah Carter is an Assistant Professor of Medicine at UC San Diego. Her research focuses on computationally modeling how DNA mutations in tumor genomes impact intracellular biological processes and cellular behaviors, and how these cellular level changes cause cancer. Dr. Carter presented on the relation between germline genetic variations and tumor development, including somatic mutation events in cancer.
Informatics Tools for Analysis of Next Generation Sequencing Studies Supported by the NCI ITCR Program
NCI's Information Technology for Cancer Research (ITCR) program promotes research-driven informatics technology across the development lifecycle to address priority needs in cancer research. ITCR supports a wide range of informatics tools to serve current and emerging needs across the cancer research continuum. The SeqSPACE panel of speakers highlighted several of the informatics tools from ITCR that are useful for next generation sequencing applications including transcriptomics, functional and clinical interpretation of variants.
Analyzing Large Scale Sequenced Based Epidemiological Studies
Suzanne Margaret Leal, Ph.D.
Professor, Molecular and Human Genetics, Baylor College of Medicine
Adjunct Professor, Department of Statistics, Rice University
Senior Research Associate, The Rockefeller University
Dr. Suzanne Leal is a Professor in the Department of Molecular and Human Genetics at Baylor College of Medicine and Director of the Center for Statistical Genetics, an Adjunct Professor in the Department of Statistics at Rice University, and a Senior Research Associate at The Rockefeller University. Her primary research interests are statistical genetics and genetic epidemiology. Currently, Dr. Leal's concentration is in the development of methods to analyze rare variants. In addition to applied work, mapping disease\trait loci, she has worked extensively in developing methods to aid in gene identification and understanding disease etiology. Dr. Leal presented on software for analyzing sequencing-based epidemiological studies and rare variant aggregation association tests.
Lessons Learned in the Application of Next Generation Sequencing to Pancreatic Cancer
Dr. Alison Klein is a Professor of Oncology at Johns Hopkins School of Medicine. She is the Director of the National Familial Pancreas Tumor Registry, the largest pancreatic cancer family registry in the world. Her current work focuses on the identification the genetic and environmental risk factors for pancreatic cancer as well as other complex genetic diseases. As part of this work, she developed PancPRO, a clinical risk assessment tool for high-risk pancreatic cancer families, that facilitates the translation of her research findings into the clinical setting. Dr. Klein presented on lessons learned in the application of next generation sequencing to pancreatic cancer.
The Application of Next Generation Sequencing Technologies in Diverse Populations and Methods for Evaluating the Pathogenicity of Variants
Dr. Carlos Bustamante is a Professor of Biomedical Data Science, of Genetics, and, by courtesy, of Biology. Additionally, he is the Founding Director of the Stanford Center for Computational, Evolutionary, and Human Genomics and the Director of Informatics at the Stanford Center for Genomics and Personalized Medicine. He is a population geneticist whose research focuses on analyzing genome wide patterns of variation within and between species to address fundamental questions in biology, anthropology, and medicine. Dr. Bustamante presented on next generation sequencing in diverse populations and evaluated pathogenicity of variants using different methods.
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes – Relationships Between Germline and Somatic Mutations
Dr. Jan Korbel is the Group Leader of the Korbel Lab in the GenomeBiology Unit of the European Molecular Biology Laboratory (EMBL). His research applies experimental and computational genomics approaches to study the extent, functional impact, as well as mutational and evolutionary origins of genetic variants. In addition, Dr. Korbel's group plays a leadership role in the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. Integrating data from somatic and germline whole genomes, DNA methylomes, transcriptomes, and clinical data from more than 2800 cancer patients, this group aims to unravel commonalities and discrepancies between the emergence of cancer types and subtypes, to facilitate molecular classification of malignancies with impact on diagnostics and treatment, and uncover causalities linking genotype, environment, and phenotype. Dr Korbel presented on the PCAWG and results from whole genome sequencing germline studies.
Deep Sequencing of 10,000 Human Genomes and Sequencing Quality Standards for Human Variation Discovery
Amalio Telenti, M.D., Ph.D.
Chief Data Scientist, Human Longevity, Inc.
Adjunct Scientist, J. Craig Venter Institute
Professor, The Skaggs School of Pharmaceutical Sciences, University of California, San Diego
Dr. Amalio Telenti is the Chief Data Scientist at Human Longevity, Inc. and Adjunct Scientist at J. Craig Venter Institute, as well as a Professor at the Skaggs School of Pharmaceutical Sciences at the University of California, San Diego. He directs HLI-X, the unit at Human Longevity, Inc. that develops advanced analytics in genomics and data sciences. He recently led the analysis of the first 10,000 deep sequenced human genomes, as well as the definition of the complete map of conservation of the regulatory structures in the human genome. Dr. Telenti presented on his experience deep sequencing 10,000 human genomes with an emphasis on the importance of sequencing quality standards for human variation discovery.
Lessons Learned in the Application of Exome Sequencing to Cancer Epidemiology Studies
Dr. Chad Huff is an Assistant Professor in the Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences at The University of Texas MD Anderson Cancer Center. His research concentrates on understanding human evolution and the genetic basis of human disease through statistical, computational, and population genomics and spans a number of human genetics subdisciplines, including disease-gene identification, mutation rate estimation, detection of recent positive selection, and reconstruction of demographic history. Dr. Huff presented on lessons learned and best practices in the application of exome sequencing to cancer epidemiology studies.
Lessons Learned in Applying Functional-Annotation for Rare Variant Analysis
Dr. Bogdan Pasaniuc is an Assistant Professor of Pathology and Laboratory Medicine at the University of California, Los Angeles (UCLA), David Geffen School of Medicine. His primary research interests are statistical and computational methods for understanding genetic risk factors for common diseases with a particular focus on the study of admixed populations. Dr. Pasaniuc presented on lessons learned and best practices in applying functional-annotation for rare variant analysis.
PrediXcan and Genotype-Tissue Expression (GTEx) Program: Use for Interpretation of Genetic Associations
Dr. Nancy Cox is the Founding Director of the Vanderbilt Genetics Institute and is a quantitative human geneticist with a long-standing research program in identifying and characterizing the genetic component to common human diseases. Her current research is focused on large-scale integration of genomic with other "-omics" data as well as biobank and electronic medical records data. Dr. Cox presented on using PrediXcan, a computational method that links genetic variation and gene activity to disease traits. In addition, she provided updates on the Genotype-Tissue Expression (GTEx) project and using this data to aid in the interpretation of genetic association studies.
ACMG Guidelines for Interpreting Sequence Variants
Dr. Richards is a Professor within the Department of Molecular and Medical Genetics at Oregon Health & Science University. The focus of her clinical research laboratory is to develop sequence-based testing for rare disorders, develop custom analysis to address copy number variants, design algorithms using analysis tools for interpretation of sequence variations, and translation of these products into clinical practice. Dr. Richards presented on the American College of Medical Genetics guidelines for interpretation.
Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
Dr. Rotunno is a Program Director in the Genomic Epidemiology Branch of the Epidemiology and Genomics Research Program in NCI's Division of Cancer Control and Population Sciences and holds an adjunct appointment to the Genetic Epidemiology Branch, of NCI's intramural Division of Cancer Epidemiology and Genetics. Her grant portfolio and research area focus on the many analytic and computational challenges accompanying the application of next generation sequencing technologies to large scale epidemiology studies. Dr. Rotunno described a study of whole exome sequencing in families at high risk for Hodgkin lymphoma which led to the identification of a predisposing mutation in the KDR gene. She described methodological aspects related to family sequencing studies and prioritization of variants.
Targeted Sequencing Of GWAS-Identified Cancer Loci In Multiethnic Populations: Lessons (Re)Learned
Dr. Peter Kraft is a Professor within the Department of Epidemiology and the Department of Biostatistics at the Harvard T.H. Chan School of Public Health. He played a leading role in the design and analysis of genome-wide association studies (GWAS) of breast, prostate, and pancreatic cancers as part of the NCI's Cancer Genetic Markers of Susceptibility (CGEMS) and PanScan projects. Dr. Kraft's current research focuses on methods that link low-frequency variation, emerging functional annotation, and risk of complex disease and genetic risk prediction using common and rare genetic variation, as well as clinical and environmental risk factors. During this webinar, Dr. Kraft discussed his experience with targeted sequencing in breast cancer genetic epidemiology studies.
Considerations in Design of Sequencing Studies – Lessons Learned from the Center for Inherited Disease Research
Dr. Kim Doheny is the Lead Co-Principal Investigator and Director of the Center for Inherited Disease Research (CIDR) at Johns Hopkins University. CIDR provides high quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to disease. On-site statistical geneticists provide valuable insight into analysis issues as they relate to study design, data production and quality control. Completed studies encompass more than 180 phenotypes across 750 projects and 800,000 samples. The impact is evidenced by more than 600 peer-reviewed papers published in 160 journals. Dr. Doheny presented on considerations regarding study design (e.g. coverage, selection of technologies) and lessons learned from CIDR regarding quality control and data cleaning.
Considerations in Design of Sequencing Studies – Lessons Learned from The Genome Institute
Dr. Elaine Mardis is the Co-Director of The Genome Institute and Professor of Genetics at Washington University. She also serves as an editorial board member of Molecular Cancer Research, Disease Models and Mechanisms and Annals of Oncology, and as a reviewer for Nature, the New England Journal of Medicine, Cell, and Genome Research. Dr. Mardis' research focuses on the application of next-generation sequencing to characterize cancer genomes and transcriptions, and using these data to support therapeutic decision-making. She presented on considerations regarding the design of whole genome and exome sequencing studies, including such topics as balancing sample size and coverage, comparisons between sequencing capture technologies, and new technologies. She also discussed experiences and lessons learned on data quality control and cleaning from The Genome Institute.
Update and Lessons Learned from Haplotype Reference Consortium
Dr. Goncalo Abecasis is Chair of the Department of Biostatistics at University of Michigan's School of Public Health. His research focuses on the development of statistical tools for identification and study of genetic variants important in human disease, and has developed gene-mapping software that has been used in hundreds of gene-mapping projects around the world. Dr. Abecasis presented an update from the Haplotype Reference Consortium related to the imputation panel, and discussed methods of combining sequencing data from different studies and sources.
Experience Using Next Generation Sequencing at NCI Division of Cancer Epidemiology and Genetics (DCEG)
Dr. Stephen Chanock is the Director of the Division of Cancer Epidemiology & Genetics (DCEG) at the National Cancer Institute. He is a leading expert in the discovery and characterization of cancer susceptibility regions in the human genome. Before becoming director of DCEG, Dr. Chanock co-led the Cancer Genetic Markers of Susceptibility project, served as Chief of both the Laboratory of Translational Genomics and the Cancer Genomics Research Laboratory, and co-directed the NCI Center for Cancer Genomics. Dr. Chanock discussed the utilization of next generation sequencing by DCEG researchers to provide insights into future studies.
Genomic Approaches to Defining Inherited Basis of Childhood Cancer
Dr. Sharon Plon is a medical geneticist who is the Director of both the Cancer Genetics Clinical and Research Programs, and the Neurofibromatosis Clinic at Texas Children's Hospital. In addition, she is a Professor of Pediatrics-Oncology and Molecular and Human Genetics at Baylor College of Medicine, and a Professor at Baylor's Human Genome Sequencing Center. Her professional interests include cancer predisposition syndromes, mechanisms of genomic instability, and the use of genome sequencing in clinical medicine. Recently, Dr. Plon's lab initiated a project in collaboration with the Human Genome Sequencing Center to develop a large-scale sequencing to identify the causative mutation or chromosome imbalance in families with unusual patterns of childhood cancer. Dr. Plon's presentation provided an update of her NCI-funded study sequencing childhood cancer families for discovery of loci associated with childhood cancer. Her talk covered topics ranging from study design, population selection, sequencing strategy, and analytic approach.
Epigenomics and Networks of Variants Underlying Common Disease and Cancer
Dr. Manolis Kellis is an Associate Professor of Computer Science at MIT, a member of the Computer Science and Artificial Intelligence Laboratory, and is the director of the MIT Computational Biology Group within the Broad Institute of MIT and Harvard. Recently, the Computational Biology Group was awarded funding to lead integrative analysis efforts of the modENCODE project and the NIH Roadmap Epigenomics Project. Dr. Kellis presented on his experience interpreting results from sequencing data by using functional annotation obtained from data sources such as ENCODE and the Roadmap Epigenomics Project. He also discussed how these methods relate to interpretation of variants from non-coding regions during whole genome sequencing.
Experience Sequencing FFPE Tumor Specimens and Implications for Integrative Studies of Germline and Somatic Variation
Dr. Tom Hudson is President and Scientific Director of the Ontario Institute of Cancer Research (OICR). He is also Co-Founder and Member of the Executive Committee for the International Cancer Genome Consortium (ICGC). Dr. Hudson is internationally renowned for his work in genomics and human genome variation. Dr. Hudson's laboratory at OICR is involved in the study of genome variation that affects cancer predisposition, progression, and response to therapy. His main project focuses on the genetic architecture of loci associated with risk to colorectal cancer. In this presentation, Dr. Hudson spoke about OICR experience with targeted resequencing from tumor specimens stored as FFPE, lessons learned in developing a large scale colon cancer tumor sequencing project and germline-somatic integration, and commented on recent ICGC-TCGA DREAM Mutation Calling challenges.
Introduction of SeqSPACE Forum and Brainstorming Key Issues
The Epidemiology and Genomics Research Program currently supports a portfolio of sequencing grants that use a wide range of study designs to investigate genetic susceptibility for a number of cancers across diverse populations. As reported at our workshop, "Making Sense of the Sequence," and in several recent publications about next generation sequencing, a clear challenge identified is the multiple approaches for applying sequencing to epidemiology studies and lack of standardized pipeline and best practices for next generation sequencing studies. This webinar series serves as a discussion forum to share lessons learned in research performed by next generation sequencing in cancer epidemiology studies. The inaugural webinar is an informal discussion where participants can brainstorm and suggest future topics and speakers for the SeqSPACE webinar series.
- Tabitha Harrison, M.P.H., Fred Hutchinson Cancer Research Center
- Frederick Schumacher, Ph.D., M.P.H., University of Southern California