NEW YORK GENOME CENTER: A YEAR IN REVIEW – 2016 A Message from Leadership

2016 was an exciting year of progress and transition at the New York Genome Center. By strengthening our reputation as a convening center of academic, medical and industry leaders in the rapidly evolving field of genomic research, we made important strides to further our mission of translating into clinical solutions for serious diseases.

This past year, we recruited distinguished faculty and staff, broadening our research focus and capabilities. Working collaboratively with member institutions, our scientists were the recipients of grants totaling more than $20 million. Our cancer genomics study with IBM’s Watson was recognized and featured at the 2016 White House Precision Medicine Initiative Summit. To meet the growing demand, we expanded our clinical laboratory services, receiving approval from New York State for constitutional whole genome sequencing.

As a young organization, we have relied on generous, forward-thinking individuals and foundations to help us make advances that will lead to treatments for patients. In 2016, philanthropic support of the New York Genome Center was catalyzed by the visionary and transformative $100 million challenge grant presented by the Simons Foundation and The Carson Family Charitable Trust. Thanks to our supporters, we are enhancing our core programs and fostering vibrant collaborations to advance the development of new treatments, therapies and therapeutics against human disease.

Thank you for your interest in and support of the New York Genome Center. We are pleased to share the important accomplishments highlighted in this report.

Sincerely,

Tom Maniatis, PhD Cheryl A. Moore Interim Scientific Director President and Chief Operating Officer

INSTITUTIONAL FOUNDING MEMBERS

1 | A Year In Review BOARD OF Tom Maniatis, PhD NYGC Interim Scientific Director DIRECTORS Director, Columbia Precision Medicine Initiative, Isidore S. Edelman Professor and Chair, Russell L. Carson Department of Biochemistry and Molecular NYGC Board Co-Chair Biophysics, Co-Founder and General Partner, Welsh, Carson, Anderson & Stowe Cheryl A. Moore NYGC President and Chief Operating Officer Ivan G. Seidenberg NYGC Board Co-Chair Herb Pardes, MD Former Chair and CEO, Executive Vice Chairman of the Board of Trustees, Verizon Communications NewYork-Presbyterian Hospital

Dafna Bar-Sagi, PhD Frank E. Richardson, MA, JD Professor of Biochemistry and Molecular Co-founder and Senior Advisory Partner, Pharmacology and Medicine, Sentinel Capital Partners Senior Vice President and Vice Dean for Science, Chief Scientific Officer, Arthur J. Samberg NYU Langone Medical Center Manager, Hawkes Financial LLC

Dennis S. Charney, MD Frank V. Sica Dean, Icahn School of Medicine at Partner, Tailwind Capital Mount Sinai; President for Academic Affairs, Mount Sinai Health System Jim Simons, PhD Chair, Simons Foundation Augustine M.K. Choi, MD President, Euclidean Capital, LLC Stephen and Suzanne Weiss Dean, Board Chair, Renaissance Technologies ; Provost for Medical Affairs, Cornell University Steven D. Singer Partner, WilmerHale Nicholas Donofrio IBM Fellow Emeritus and EVP Innovation Allen M. Spiegel, MD and Technology, IBM (retired) The Marilyn and Stanley M. Katz Dean, Albert Einstein College of Medicine, John B. Ehrenkranz Executive Vice President and Chief Chief Investment Officer, Ehrenkranz Partners Academic Officer, Montefiore Medicine

Anthony B. Evnin, PhD Samuel L. Stanley Jr., MD Partner, Venrock President,

Lee Goldman, MD, MPH Bruce Stillman, PhD Dean, Faculties of Health Sciences and Medicine, President and CEO, Chief Executive, Cold Spring Harbor Laboratory Columbia University Medical Center Craig B. Thompson, MD John Havens President and CEO, Partner and Non-Executive Chair, Memorial Sloan Kettering Cancer Center Napier Park Global Capital Kevin J. Tracey, MD Weslie R. Janeway President and CEO, President, Pyewacket Foundation Feinstein Institute for Medical Research, Professor of Neurosurgery and Molecular Richard P. Lifton, MD, PhD Medicine, Hofstra Northwell School of Medicine President, The

Edison T. Liu, MD President and CEO, The Jackson Laboratory

INSTITUTIONAL ASSOCIATE MEMBERS FOUNDING TECHNOLOGY MEMBER

A Year In Review | 2 hroughout the past year, the New York Genome Furthering our mission to enhance the life sciences Center (NYGC) celebrated a number of important in New York, the NYGC will launch a life science T accomplishments. innovation incubator at our facility in partnership with Johnson & Johnson Innovation and New York State. We were pleased to welcome as Called JLABS @ NYC, the incubator will make use our newest Institutional Associate Member, bringing our of our third-floor space to host up to 30 life science member institutions to a total of 18. Our collaboration with startup companies in , pharmaceutics, Princeton, a world-renowned research university, and its medical devices and consumer health. This new Lewis-Sigler Institute for Integrative Genomics strengthens partnership, announced in Governor Cuomo’s annual the NYGC’s focus on clinically actionable genomics State of the State address in January 2017, generated and science. Princeton’s faculty have the opportunity to wide print, broadcast and social media coverage. participate in the NYGC’s robust scientific culture, including Governor Cuomo has proposed $17 million in funding scientific symposia, workshops, conferences and training for capital investments to support this initiative. JLABS programs. This new partnership paves the way for new @ NYC, scheduled to open in 2018, will offer an invaluable collaborations and innovation between researchers at opportunity for the NYGC and our member institutions to Princeton, the Lewis-Sigler Institute, the NYGC and our establish new collaborations and partnerships with these other member institutions. emerging companies.

Our CLEP-certified Clinical Lab received conditional approval from New York State to offer clinical constitutional NYGC Research whole genome sequencing testing for undiagnosed In 2016, researchers at the NYGC helped contribute to diseases and presymptomatic individuals. This is an advancements in the field of genomics through their expansion of our clinical genomic services, which includes translational research on a wide range of diseases. Their constitutional exome sequencing for undiagnosed diseases, findings were published in more than 50 high-impact reference sequencing and Sanger validations. We are scientific journals. awaiting approval from New York State to conduct whole genome and transcriptome testing for cancer. Our scientists conducted an array of investigations, including research on renal cell carcinoma, In fall 2016, Governor Cuomo appointed Cheryl A. Moore, autism and breast cancer. The Bioinformatics team President and Chief Operating Officer of the NYGC, as also developed and will shortly launch the MetroNome Co-Chair of the Regional Economic database, a web application that allows researchers Development Council (NYCREDC). She and Co-Chair to explore data visually, with the goal of correlating Winston Fisher, Executive Vice Chair of Fisher House genotypes with phenotypes. The system accepts genomic Foundation, are working to help bring new investments sequencing and clinical data from any research project. and growth into the New York City area economy. Participating researchers can explore their data in an

JLABS @ NYC COMING TO THE NEW YORK GENOME CENTER

“ The new, vital incubator JLABS will be the catalyst that pushes our state into the forefront of this exciting field. I look forward to working with Johnson & Johnson and the New York Genome Center to build momentum in the life science industry and establish New York as the home of discoveries that will drive the economy and create a better future for all.”

— Andrew Cuomo Governor, New York State

3 | A Year In Review MISSION The New York Genome Center is an independent, nonprofit academic research organization at the forefront of transforming biomedical research and clinical care with the mission of saving lives.

A collaboration of renowned academic, medical and industry leaders in New York and other partners throughout the country, the New York Genome Center focuses on translating genomic research into clinical solutions for serious diseases. New York Genome Center member institutions and partners are united in this unprecedented collaboration of technology, science and medicine.

We advocate and educate, sharing our findings and discoveries with the scientific, medical and thought leadership communities. We integrate our genomic research with cutting-edge technologies and leading physician-scientists so that patients around the world can benefit from more effective clinical treatments.

A Year In Review | 4 “Our collaborative work with the NYGC is on the frontier of molecular medicine. We hope our research can advance knowledge of how non-coding as well as protein-coding regions of the genome can contribute to neurological disease. We really like the opportunity the NYGC offers to interact with other genomic scientists throughout the city and the world, and it certainly accelerated our progress. The collaboration stimulated better work and created a synergistic environment that enhanced our research and made the whole process a lot more fun.”

— M. Elizabeth Ross, MD, PhD Nathan Cummings Professor of Neurology and Head, Laboratory of Neurogenetics and Development Director, Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine

5 | A Year In Review NUMBER OF WHOLE GENOME 20,000SAMPLES SEQUENCED interactive, visual interface and organize data along many dimensions. MetroNome enables investigators to search for genomic differences across large populations, investigate the effects of genomic variants and relate them to phenotypic conditions. The Bioinformatics team’s research in 2016 has resulted in more than a dozen publications in journals such as Nature, The American We strengthened collaborative research Journal of Human Genetics and The Journal of Clinical projects with our Institutional Founding Investigation. Members and were jointly awarded a National Cancer Institute grant with Weill Cornell Marcin Imielinski, MD, PhD, discovered a new class of Medicine for a specialized genomic data mutations in cancer that may represent a novel class of driver in liver, lung, thyroid and stomach cancer, and his center, with Michael Zody, PhD, Senior findings were subsequently published in Cell. Neville Director, Computational , as the Sanjana, PhD, utilized CRISPR, an advanced gene-editing co-principal investigator at the NYGC. technique, to analyze non-coding regions of the human genome that drive drug-resistant cancer. His study, which may offer new treatment options for patients with or determining which alleles of genetic variants lie in the melanoma and other cancers, was published in Science same chromosome and may act together. This study, which and featured in an article in TIME. was published in Nature Communications, is part of her lab’s ongoing work to uncover general rules of the genomic Joseph Pickrell, PhD, and Yaniv Erlich, PhD, completed sources of human traits and diseases. several breakthrough genome-wide association studies in 2016. One study discovered multi-tasking genes that Collaborative Projects influence a wide variety of human traits and conditions, Working together with researchers from our member identifying some unexpected connections between institutions, as well as renowned scientists worldwide, the diseases. This research could provide a powerful new NYGC participated in many collaborative research projects tool for scientists to identify shared causal relationships on a wide range of diseases, including pediatric and adult between diseases and better understand how diseases cancer, autism, Alzheimer’s disease, ALS, arthritis, interrelate. In another study, Drs. Pickrell and Erlich glaucoma, brain injury, schizophrenia and hemophilia. deployed advanced data analytics and genome-wide association by proxy, using the DNA of patients’ families to The NYGC’s Center for Common Disease Genomics map risk factors. They uncovered 17 new disease-causing received funding from the National Human Genome mutations for Alzheimer’s disease, cardiac disease and Research Institute to help us expand our research on diabetes. Both studies were published in Nature Genetics. autism, asthma and Alzheimer’s disease.

Research done by Tuuli Lappalainen, PhD, and her team The Cancer Genomics Alliance study, a joint initiative resulted in the development of phASER, a novel method and between the NYGC and IBM, was recognized and software tool that substantially improves haplotype phasing, highlighted at the 2016 White House Precision Medicine

A Year In Review | 6 The New York Genome Center participated in many collaborative research projects on a wide range of diseases, including pediatric and adult cancer, autism, Alzheimer’s disease, ALS, arthritis, glaucoma, brain injury, schizophrenia and hemophilia.

As part of our efforts to advance the field of epigenomics, our scientists collaborated on a whole genome bisulfite sequencing pilot study with researchers at Albert Einstein NUMBER OF PROJECTS College of Medicine. We developed a whole genome COMPLETED bisulfite sequencing library prep compatible with the HiSeq X, reducing the cost of whole genome bisulfite sequencing by two-thirds and cutting the turnaround time in half, 1,000 making it accessible to more researchers worldwide.

Initiative Summit. In collaboration with IBM, our With support from the Sohn Conference Foundation, our Founding Technology Member, we are working to build scientists are working closely with researchers at Columbia a comprehensive and open repository of genetic data to University, Memorial Sloan Kettering Cancer Center and accelerate cancer research. NYGC scientists sequenced the on a collaborative project that involves DNA and RNA from 200 cancer patients being treated at our whole genome and RNA sequencing to find potential new member institutions. We are housing the contributed data clinical treatments for children with acute lymphoblastic and training Watson’s cognitive computing capacities for leukemia and neuroblastomas. With a grant from the genomic analysis. The genetic information and clinical data Hereditary Disease Foundation and the W.M. Keck from the patients were fed into Watson to review massive Foundation, we are collaborating with researchers at amounts of medical evidence to help identify existing drugs Columbia University and the Massachusetts Institute of that may be candidates to potentially target patients’ Technology on a study to find modifiers of Huntington’s cancer-causing mutations. All clinically actionable results disease. These research findings may also be relevant in other were shared with treating physicians. neurological diseases, including autism and schizophrenia.

7 | A Year In Review Faculty Update NYGC scientists were awarded several prestigious grants. Rahul Satija, PhD, received a New Innovator Award from the National Institutes of Health to fund NUMBER OF INVESTIGATORS research focusing on how the interaction between molecular and environmental factors governs cell behavior. Yaniv Erlich, PhD, and Joseph Pickrell, PhD, were awarded a grant from the National Breast Cancer Coalition to expand 260 the services of DNA.Land, the nonprofit web-based platform they created that houses genomes from 40,000 people, To advance collaborative efforts on cancer genomics, for a targeted collection of data of breast cancer Nobel Laureate Harold Varmus, MD, Senior Associate Core patients. Dan Landau, MD, PhD, was the recipient of a Member, NYGC, and Lewis Thomas University Professor of Stand Up to Cancer Innovative Research Grant for a project Medicine, Weill Cornell Medicine, established the New York with Weill Cornell Medicine, focused on a new mathematical Cancer Genomics Research Network. Dr. Varmus convenes approach to design combination therapies for chronic monthly meetings at the NYGC with leading cancer lymphocytic leukemia. researchers and clinicians from our Institutional Founding Members and other key academic institutions around the Our Center for Genomics of Neurodegenerative Disease’s world. The objective of this multidisciplinary approach is to ALS Consortium, led by Hemali Phatnani, PhD, was joined help set critical priorities in translating genomic science into by two new members, The Jackson Laboratory and the more effective treatment options for all cancer patients in University of California, Irvine. The Consortium now New York and beyond. includes 15 leading institutions in the and abroad. Scientists and clinicians work collaboratively to Since its inception, the NYGC has attracted world-class apply state-of-the-art clinical and functional genomics scientists whose genomic expertise – including single cell together with bioinformatics to study ALS disease genomics, genome engineering, population and evolutionary mechanisms and better understand how mutations genomics, technology and methods development, statistics, underlying ALS cause disease. The target of this global computational biology and bioengineering – bring a multidisciplinary effort is whole genome sequencing and multidisciplinary and in-depth approach to the evolving analysis of 3,200 clinically well-annotated ALS samples field of genomics. In 2016, we recruited two distinguished within the next three years to enhance early diagnosis researchers, Drs. Neville Sanjana and Simon Tavaré, and effective drug discovery. to our faculty.

A Year In Review | 8 Neville Sanjana, PhD, joined the NYGC as a Core Cognitive Sciences and completed his undergraduate Member and Assistant Investigator. Dr. Sanjana’s scientific education at Stanford University. In his postdoctoral expertise includes genome engineering, functional genomic research, Dr. Sanjana helped develop two classes of screening using programmable nucleases, autism genetics targeted nucleases for genome engineering: TALEs and synaptic pathophysiology. He holds a joint appointment ( activator-like effectors) and the at New York University as an Assistant Professor in the microbial immune system-derived CRISPR (clustered Department of Biology and the Center for Genomics and regularly-interspaced short palindromic repeats) Systems Biology and an associate faculty appointment enzymes. He uses these genome-engineering tools in with the Institute for Systems Genetics at New York a variety of contexts to understand how genetic University Langone Medical Center. variants affect human health and disease.

Previously at the of Harvard and Simon Tavaré, PhD, joined the NYGC as a Senior the Massachusetts Institute of Technology and in the Researcher while continuing his appointments as Departments of Brain and Cognitive Sciences and the Director of the Cancer Research UK Cambridge Bioengineering at the Massachusetts Institute of Technology, Institute and Professor in the Departments of Oncology Dr. Sanjana was a postdoctoral scientist in the laboratory and Applied Mathematics and Theoretical Physics of Dr. Feng Zhang. Dr. Sanjana received his PhD from at the University of Cambridge. Dr. Tavaré is widely the Massachusetts Institute of Technology in Brain and recognized as one of the world’s leading experts in

9 | A Year In Review statistics and probability in computational biology. His research interests include statistical genetics, evolutionary approaches to cancer and stochastic computation.

Dr. Tavaré received his BSc degree, MSc degree and PhD in probability and statistics from the University of Sheffield, UK. He spent 25 years in academia in the United States before moving to Cambridge in 2004. He was elected a Fellow of NUMBER OF COLLABORATING the Academy of Medical Sciences in 2009 and named a INSTITUTIONS Fellow of the Royal Society in 2011. Dr. Tavaré currently serves as President of the London Mathematical Society. 89 Dr. Tavaré is helping to forge connections and collaborations between the NYGC and other cancer research centers worldwide.

A Year In Review | 10 “ W e chose to work with the NYGC because of its high-quality sequencing services, coupled with its skilled bioinformatics team, which provided the flexibility to meet the unique needs of our study. We’ve had a tremendously positive experience collaborating with the NYGC faculty and staff. The project managers that we have worked with have been organized, cordial and highly responsive. Communication about questions, data transfers, meetings, budgets and timelines have been addressed promptly and thoroughly.”

— Brian J. Reid, MD, PhD Full Member, Divisions of Public Health Sciences and Human Biology, Fred Hutchinson Cancer Research Center; Professor of Medicine and Adjunct Professor of Genetics, University of Washington

11 | A Year In Review Education & Outreach As part of our educational mission, we hosted many Using next-generation sequencing, the NYGC scientific meetings, workshops, conferences and lectures in can sequence genomes more efficiently and cost effectively than previously possible — more 2016. We held Evening Talks, our lecture series for the than 500 whole genomes are sequenced general public on advances in genomic science, sponsored each week. by the New York Community Trust–Pyewacket Fund. We hosted Five Points lectures for the scientific community, featuring leading researchers from around the country We generated 9,000 terabytes of data — the and abroad. In addition, the NYGC held well-attended equivalent of 4.5 million Netflix movies. workshops for the medical community on single cell genomics, epigenomics, sequencing informatics and ancestry. We used more than 22.4 million core In October, the NYGC hosted its inaugural Single Cell hours of compute, which would take 1,269 years on a typical computer. Genomics Day: A Practical Workshop to provide researchers a basic overview of single cell sequencing. The event, organized by the NYGC’s Rahul Satija, PhD, attracted Also in September, the NYGC hosted its first Sequencing 200 attendees from 30 academic and commercial institutions. Informatics Workshop, which was organized by The program focused on technology development, molecular Michael Zody, PhD, Senior Director, Computational protocols and computational analysis. Biology. Colleagues at our Institutional Founding Members, graduate students, postdocs, faculty and research laboratory staff learned the basics of sequence data alignment, data analysis and identifying somatic variations in cancer samples. Participants also learned how to read and understand common file formats and analyze RNA-seq data for expression and differential expression. This past September, the NYGC hosted the first DNA.Land User Group Meeting. This unique “family reunion” was In May, the NYGC hosted our second annual New York attended by more than 100 people and attracted media Epigenomics Symposium. This day-long event, organized coverage on Fox 5 News. The panel featured best-selling by NYGC’s Will Liao, PhD, was attended by more than 160 author A.J. Jacobs and NYGC’s Yaniv Erlich, PhD, people. It included sessions that explored recent discoveries, Joesph Pickrell, PhD, Dina Zielinski, Jie Yuan and Sophie Zaaijer. ongoing work and novel methods in the field of epigenomics.

A Year In Review | 12 Looking Forward

Thanks to the continued support of our donors, the New York Genome Center has made important strides in contributing to the advancement of knowledge in the field of genomics.

The NYGC harnesses the diversity of New York’s leading academic and medical institutions to drive scientific discoveries that aim to improve medical treatment for patients. Our momentum is strong, and the upcoming year holds great promise for continued leaps forward.

Our progress is made possible by the incredible generosity of friends that allowed us to put in place the necessary personnel, faculty, technology and infrastructure to help us translate genomic research into actionable solutions to improve and save lives.

We continue to benefit from the Simons Carson challenge grant, wherein NYGC Directors Jim Simons and Russ Carson match each philanthropic gift made to the NYGC over the next two years. The generosity of our donors inspires others to invest in our work, and our donor base continues to expand. We are grateful for the confidence these gifts signify as we move toward our $100 million goal.

For more information on how to help further our progress, please contact:

Kathleen Kearns Vice President, Development and Communications Email: [email protected] Phone: 646.977.7026

New York Genome Center 101 Avenue of the Americas, 7th Floor New York, NY 10013

13 | A Year In Review NYGC DONORS William Randolph Hearst Foundation

AE Family Foundation Hereditary Disease Foundation

The ALS Association Weslie R. Janeway

Bloomberg Philanthropies Paul Tudor Jones

Bright Funds Foundation JSRM Foundation

Megan and Bob Burbridge Ruth Ellen Kaplan

The Carson Family Charitable Trust Marie-Josée and Henry R. Kravis Foundation

Lisa and Dick Cashin Elaine and Ken Langone

Robert and Jennifer Darnell Christy and John Mack Foundation

Anthony J. and Christie B. de Nicola Robert B. Millard

Bucky Dent/Embraced by Love National Breast Cancer Coalition

Stanley and Fiona Druckenmiller The New York Community Trust – Pyewacket Fund Andra and John B. Ehrenkranz Dorothy Oertel-Albright Roger W. and Carol B. Einiger Philanthropic Fund of the Jewish Communal Fund Project ALS

Barbara and Burton Einspruch Philanthropic Fund Frank E. Richardson of the Dallas Jewish Community Foundation David Rockefeller Empire State Development Corporation The Sackler Trust Judith and Anthony Evnin Arthur and Rebecca Samberg Gerald J. & Dorothy R. Friedman New York Foundation for Medical Research, Inc. Gleniss Schonholz

Eugene and Emily Grant Family Foundation Phyllis and Ivan Seidenberg

Bill Harvey The Honorable Colleen McMahon and Frank V. Sica John P. Havens Simons Foundation Peter H. and Louise Havens The Alfred P. Sloan Foundation Andria and Paul Heafy The Sohn Conference Foundation

The Speyer Family Foundation, Inc.

The Starr Foundation

Mr. & Mrs. Anthony Tamer

Target ALS

Three Little Pigs Foundation (William E. Ford)

The Tow Foundation

Sue and Edgar Wachenheim III Foundation

Lulu C. Wang

Brian F. Wruble

Mortimer B. Zuckerman

A Year In Review | 14 CONTACT US CONNECT WITH US

101 Avenue of the Americas New York, NY 10013

646.977.7000 [email protected] www.nygenome.org