Message from Leadership
The New York Genome Center (NYGC) continues to play a vital role as a convening hub for scientific collaboration and innovation in New York.
In June, we hosted the second annual meeting of the ALS Consortium, a worldwide collective of ALS researchers and clinicians, led by NYGC’s Center for Genomics of Neurodegenerative Disease. The ALS Consortium is sharing and analyzing genomic and clinical data of ALS patients through MetroNome, the NYGC-developed data visualization interface. Just prior to the meeting, members of the ALS Consortium were credited as contributing co-authors to a study, published in Neuron, that identified a new gene associated with ALS.
In August, NYGC’s Genome Center Cancer Group held a summer retreat for leaders of our region’s cancer research community to discuss Polyethnic-1000, a new multi-institutional endeavor to study the genomics of cancer across the ethnically-diverse communities of New York City. We are grateful to The Mark Foundation for Cancer Research for their recent gift of $1 million for Phase 1 of this project. We will continue our efforts to secure additional funding for the second and third phases of this important initiative.
These scientific meetings are of critical importance to our efforts to advance genomic science – along with the many other collaborations and innovative research activities led by our teams. Our Affiliate Membership Program (AMP), which was launched late last year, has grown to include 53 members. We look forward to hosting a special AMP event on October 22 to foster collaborative research in our community. And as of late June, our facility now includes JLABS @ NYC, a collection of 30 life science companies, selected for support by Johnson & Johnson Innovation, who are our new neighbors – and potential new collaborators – on our third floor.
We are pleased to announce that Simon Tavaré, former Director of the Cancer Research UK Cambridge Institute, and Professor in the Departments of Oncology and Applied Mathematics and Theoretical Physics at the University of Cambridge, who has been engaged with the NYGC as a Senior Researcher for the past two years, has relocated to New York to take up a position with Columbia University leading the development of the Irving Institute for Cancer Dynamics. He will become a Senior Associate Core Member with the NYGC, beginning September 19. He will also lead a community-wide working group, building collaborations in cancer analytics at the NYGC.
We are especially excited to be welcoming a new member to the NYGC faculty. David Knowles, PhD, currently a postdoctoral research fellow at Stanford University and an expert in the development of machine learning methodologies for functional genomics, will join the NYGC faculty in January 2019 with a joint academic appointment at Columbia University. We look forward to his joining our team and to his further contributions to the field of statistical genetics, and to deciphering the role of intergenic and intronic DNA sequence variants in human genetic disease mechanisms.
It’s an exciting time at the NYGC, with much to celebrate and recognize among our team’s accomplishments. The newsletter below is a showcase of NYGC’s remarkable achievements and ongoing excellence.
|Tom Maniatis, PhD
Scientific Director and Chief Executive Officer
|Cheryl A. Moore
President and Chief Operating Officer
In the News
Funding supports the new multi-institutional endeavor, led by the Genome Center Cancer Group, to improve outcomes for patients by increasing the participation of ethnic groups currently underrepresented in existing genomic databases. READ MORE
The New York Genome Center is honored to partner with Johnson & Johnson Innovation and New York State to bring the JLABS network to New York, further strengthening the life sciences sector. READ MORE
The project-oriented course for graduate students from multiple universities in the New York area, taught by NYGC Core Faculty Members Tuuli Lappalainen, PhD, and Neville Sanjana, PhD, and featuring an array of guest speakers, returns to NYGC this September. READ MORE
Lancet Study Published; Cancer Cell Mutation Detection Tool Receives NIH/NCI Grant for Further Development
“New Cancer Somatic Variant Caller Promises Greater Accuracy,” is how GenomeWeb heralded the study published this spring, in Communications Biology, describing Lancet, the novel computational method developed by the NYGC Bioinformatics team.
Lancet represents a major advance in the identification of tumor cell mutations, known as somatic variant calling, by bringing new dimension and color to the process. The tool deploys a new micro-assembly approach that examines tumor and normal cell data at the same time, representing a more powerful way of identifying mutations since researchers previously were dependent on analyzing sequence data from tumor and normal cells separately. Additionally, Lancet uses a data structure called a colored de Bruijn graph, offering researchers a visualization aid to confirm variants of clinical importance. NYGC’s Giuseppe Narzisi, PhD, Lead Bioinformatics Scientist, and Michael Zody, PhD, Senior Director, Computational Biology, are first and senior authors, respectively, on the study. (Access links to the study, the GenomeWeb article and NYGC press release here.)
Following publication of the Lancet study, the Bioinformatics team was awarded a new R21 grant from the National Institutes of Health (NIH) and National Cancer Institute (NCI) to support further development of the tool for the next two years. The team project, described in detail here, will include development and testing of Lancet’s novel framework using a combination of synthetic and genuine datasets designed to assess its variant calling abilities under diverse sequencing conditions, tumor clonality and sequencing platforms. The grant is funded specifically by the NIH Informatics Technology for Cancer Research program, a trans-NCI program supporting investigator-initiated cancer research informatics technology projects across the development lifecycle.
In May, Dr. Narzisi, the project’s principal investigator (PI), attended the yearly grantee meeting at the main NIH campus in Bethesda to present an overview of the project. Joining Dr. Narzisi was Michael C. Schatz, PhD, Bloomberg Distinguished Associate Professor, Johns Hopkins University; Adjunct Associate Professor of Quantitative Biology, Cold Spring Harbor Laboratory (CSHL), and Adjunct Assistant Professor of Computer Science, Stony Brook University, who serves as co-PI on the project. Dr. Narzisi had previously developed a micro-assembly variant caller Scalpel while at CSHL.
Other recent research/publications with contributions by the NYGC Bioinformatics team include the following:
Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data, a study with the Rockefeller University and the Hospital for Special Surgery, published in the May issue of Arthritis & Rheumatology, uncovering important genetic patterns that may help clinicians develop optimal pain management and treatment strategies for arthritis patients. The study included microscopic study of patient tissues and deployed such data analysis tools as consensus clustering and support vector machine learning to integrate RNA sequencing data into tissue analysis data to model and predict disease subtypes. Senior Bioinformatics Scientist Phaedra Agius, PhD, was one of the five equally-contributing lead authors; other NYGC co-authors are Nicolas Robine, PhD, Assistant Director, Computational Biology; Heather Geiger, Senior Bioinformatics Analyst; Mayu Frank, Consultant, Darnell Lab; and NYGC Founding Director Robert Darnell, MD, PhD. Read more about the study here.
taxMaps: Comprehensive and highly accurate taxonomic classification of short-read data in reasonable time, published in the May 28 edition of Genome Research. This publication, co-authored by Andre Corvelo, PhD, Senior Bioinformatics Scientist; Wayne Clarke, PhD, Bioinformatics Scientist; Nicolas Robine, PhD, Assistant Director, Computational Biology; and Michael Zody, PhD, Senior Director, Computational Biology, describes the team’s novel computational tool capable of delivering high classification accuracy within comprehensive genomic databases at greater speed and less computational cost than existing tools. The tool’s performance and comprehensiveness make it highly suitable for unbiased contamination detection in large-scale sequencing operations, microbiome studies comprising a large number of samples, and for applications where delivery time and accuracy are both critical factors, such as pathogen identification from clinical or environmental samples.
Organoid profiling identifies common responders to chemotherapy in pancreatic cancer, a study led by Cold Spring Harbor Laboratory’s David Tuveson, MD, PhD, published in the May 31 edition of Cancer Discovery, facilitating personalized treatments for pancreatic cancer patients. The Bioinformatics team’s work included assessing RNA levels in patient-derived individual organoids — hollow spheres of cells cultured from tumors — to determine gene signatures that predict sensitivity to different types of chemotherapies. Read more about the study and NYGC contributions here.
YES1amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics, a study with scientists at Memorial Sloan Kettering Cancer Center, reported in the June 6 edition of Proceedings of the National Academy of Sciences, identifying one way that lung cancer cells outsmart a common targeted drug therapy. The results pave the way for improved treatments. Read more about the study and NYGC contributions here.
Technology Innovation Lab
CITE-seq and Cell Hashing Protocols Included in BioLegend’s TotalSeq™ and 10X Genomics Kits
NYGC’s Technology Innovation Lab continues to develop new technologies for enhanced single-cell analysis and make them widely accessible to the scientific community.
In May, the lab released protocols for making its novel methods CITE-seq and Cell Hashing compatible with 10x Genomics’ new 5P/V(D)J kit. This release extension allows researchers to measure proteins and multiplex experiments using the lab’s methods while also taking advantage of 10x’s assay to obtain both the gene expression profile and T-cell receptor and B-cell immunoglobulin repertoires from the same input sample. This allows users to analyze the adaptive immune response inside complex tissue samples, observe the effects of immunotherapies, and investigate complex autoimmune, infectious and other immune diseases.
The lab also continues to have many requests to speak about its work, with Marlon Stoeckius, PhD, Senior Research Scientist, and Peter Smibert, PhD, Manager, Technology Innovation, presenting at the American Association of Immunologists annual meeting in Austin, Texas, and giving webinars for GenomeWeb and Nature, respectively. (You can view the 10X sponsored Nature webcast after submitting free registration information here). In addition, Dr. Stoeckius was invited to present at the Antibody Industrial Symposium in Montpelier, France, and Eleni Mimitou, PhD, Senior Research Scientist, presented at the NYC Illumina user group meeting.
As part of an exclusive worldwide license and collaborative research agreement, the lab is also continuing its work with BioLegend, a developer and manufacturer of antibodies and reagents for biomedical research. Currently, BioLegend has a CITE-seq-focused kit of over 200 oligo-conjugated antibodies available for purchase under the brand name TotalSeq™, as well as Cell Hashing reagents for both human and mouse cells. The lab and BioLegend are engaged in ongoing efforts to develop further applications for the lab’s technologies.
In June, Will Stephenson, PhD, Senior Research Engineer, published a single-author paper in Micro and Nano Systems Letters describing a novel technology for droplet microfluidics, which has emerged as a promising technique to perform high-throughput, massively-parallel chemical and molecular biological reactions. In his efforts to build modules to recapitulate common laboratory operations in droplets, Dr. Stephenson noted that there was no good option for washing magnetic particles in high-throughput droplet microfluidic methods. By using serial operations of fluid injection and droplet splitting, Dr. Stephenson was able to achieve high particle recovery and high wash efficiency. This work has important “lab-on-chip” applications for miniaturization and automation of molecular biology protocols.
New Genomic Services Offerings, Outreach Initiative Launched
NYGC’s Sequencing Operations – encompassing NYGC’s Production Lab, Methods Development Lab and Genomic Services Project Management teams – has had a busy spring/summer, rolling out new service offerings as well as launching an outreach initiative to showcase its range of services to researchers.
In collaboration with Albert Einstein College of Medicine researchers and NYGC computational biologists, Sequencing Operations has now fully developed and started offering its whole genome bisulfite sequencing (WGBS) assay as a service. Bisulfite treatment of DNA is a standard approach to study DNA methylation, a form of DNA modification that plays an important role in an array of biological processes. Coupled with next-generation sequencing, WGBS allows DNA methylation to be evaluated at a genome-wide scale. However, bisulfite conversion is a harsh treatment of DNA, leading to substantial degradation and short fragments of DNA, which makes it difficult to take advantage of the most economical sequencing modalities of the relatively longer reads of the newest generation of Illumina sequencers since short fragments will lead to overlapping reads and redundant information. The NYGC-developed assay enables the generation of relatively longer DNA fragments while maintaining the relatively low DNA input requirements, thus representing an advance in efficiency and cost. Whole-genome bisulfite sequencing with improved accuracy and cost, the team’s manuscript describing the performance of the method, was published in Genome Research in August.
The team also recently completed a Cell Hashing pilot project with Mount Sinai researchers, generating data for 20,000+ cells in a single experiment by leveraging the doublet-detection and multiplexing power of this innovative single-cell technology developed in the NYGC Technology Innovation Lab. Sequencing Operations plans to make Cell Hashing a standard service option for researchers.
This spring, the Project Management team also began a new outreach initiative to visit all of NYGC’s institutional founding member (IFM) sites over the next six to 12 months to discuss current service offerings, showcase new and exciting initiatives and research at NYGC, and network with the research community to learn about how NYGC can best serve its IFMs.
In May, IFM visits were held at Weill Cornell Medicine (WCM) and Stony Brook University. Research presenters at both events were Hemali Phatnani, PhD, Director, Center for Genomics of Neurodegenerative Disease; Peter Smibert, PhD, Manager, Technology Innovation; and Mike Zody, PhD, Senior Director, Computational Biology. Marcin Imielinski, MD, PhD, NYGC Core Faculty Member and Assistant Professor of Computational Genomics and Assistant Professor of Pathology and Laboratory Medicine at WCM, joined the group at the WCM event.
Rapid WGS Analysis Guides Treatment Plan for Children with Nephrotic Syndrome
Get a “genetic diagnosis” early – and avoid prolonged and potentially detrimental treatments in patients for whom it is inappropriate.
That is an important ongoing goal in precision medicine – and a key part of the ongoing work of NYGC’s Clinical Lab, which is licensed to offer whole genome sequencing (WGS) services, among other diagnostic tests, to patients across the country when ordered by their physicians.
One of the lab’s current projects is working with Columbia University Medical Center (CUMC) physicians, with pilot funding by CUMC’s Precision Medicine Initiative, to return rapid WGS results (within two weeks) to guide clinical management of children and young adults with nephrotic syndrome (NS), a kidney disorder that is a major contributor to end-stage renal disease, at which point patients need dialysis or kidney transplant to stay alive.
Traditionally, the treatment plan for these patients has been as follows: give them a full course of steroids to induce remission; then, if remission fails, perform a kidney biopsy, with the majority of patients then exposed to high-dose prolonged immunosuppressive therapy following biopsy, irrespective of the individual genetic makeup, prior to undergoing dialysis or transplant.
Recent research has revealed, however, that more than 35 genes are implicated in forms of NS, and a genetic cause can be found in the approximately 20-30% of patients below the age of 18 who have poor response to steroid therapy. Patients with certain monogenic forms of NS are also usually resistant to treatment with immunosuppression and – most significantly – the disease rarely recurs after kidney transplantation for these patients.
To date, the CUMC/NYGC initiative has conducted WGS testing on five patients. Based on findings from the testing, returned quickly to physicians, two of these patients will now bypass other treatments and become eligible for transplant.
CGND’s ALS Consortium Contributes to New ALS Gene Discovery, Holds Information-Sharing Meeting at NYGC
“Our commitment to sharing research insights and data is essential to expanding our understanding of ALS. You are an outstanding group of scientists, and we are proud to work with you.”
So concluded the note of thanks from Lucie Bruijn, PhD, MBA, Chief Scientist, ALS Association, and Hemali Phatnani, PhD, Director of NYGC’s Center for Genomics of Neurodegenerative Disease (CGND), sent to the attendees of the second-ever ALS Consortium Meeting, held June 24-26, 2018 at the NYGC.
More than 120 clinicians, scientists, geneticists, computational biologists and industry partners from around the globe gathered at NYGC for this meeting, presenting their latest findings and discussing the opportunities and challenges in advancing collaborative ALS research. The group was approximately double in size to the inaugural ALS Consortium Meeting held at the NYGC in 2016.
This year’s meeting was kicked off by a keynote speech by Cori Bargmann, PhD, Head of Science at the Chan Zuckerberg Initiative, Head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, and the Torsten N. Wiesel Professor at The Rockefeller University, and included updates from other consortia and partnerships working closely with the ALS Consortium, including Answer ALS, Target ALS, Project MinE, Genomic Translation for ALS Care (GTAC), and The DIALS (Dominant Inherited ALS) Network. View the full agenda of the meeting here.
Launched by Dr. Phatnani just over three years ago, the CGND’s ALS Consortium has grown to include 27 institutional members across the globe. Established with the support of The Tow Foundation and The ALS Association, its goal is to establish a framework for applying state-of the-art genetics, genomics and bioinformatics to the study of ALS to help facilitate early diagnosis and effective drug discovery. Through MetroNome, a data repository and visualization tool developed at the NYGC, the CGND makes available to its ALS Consortium members and the research community at large an ever-growing resource of genomic sequencing and clinical data, with several thousand clinically well-annotated ALS samples currently available through the tool. Christian Stolte, Data Visualization Designer, NYGC, provided a formal presentation on MetroNome at the meeting, and workstations were also available for attendees to receive on-on-one demos of the tool.
The CGND’s ALS Consortium also recently reached a key milestone in its data-sharing mission, having contributed to the identification of a novel gene associated with ALS – KIF5A – in a study led by John Landers, PhD, at UMass Medical School, and Bryan Traynor, MD, PhD, at the National Institute on Aging at the National Institutes of Health. The discovery, published as a cover story in Neuron, further implicates the role of defects in the axon, the threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells, as a common factor in the disease and a potential target for new drug development. Dr. Phatnani is credited as an individual co-author on study with the NYGC ALS Consortium a group co-author. In a press release, Dr. Landers noted that ALS Association funding to study collaborators, including the NYGC ALS Consortium, was “instrumental” to the success of what he termed “the largest collaborative genetics effort in ALS.” Dr. Phatnani and the ALS Consortium are also co-authors of another recent study, Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism, published in eLife in July.
In August, the preprint Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis, a CGND collaborative study with the Lundeberg group of Stockholm’s SciLifeLab and the Bonneau group of NYU and the Flatiron Institute, was posted on bioRxiv. In this study, the researchers used an emerging method for spatially resolved RNA sequencing, termed Spatial Transcriptomics, combined with a novel computational approach, to assemble a transcriptome-wide atlas of disease-driven gene expression changes in ALS. The atlas is in 4D, spanning the dimensions of length, width, and depth, and time, for three mouse genotypes and also maps the disease in spinal cord sections from ALS patients. The atlas details the molecular pathology of ALS not only in individual cell types, but also within distinct subpopulations of each cell type present in the spinal cord, across space and time, and also identifies early changes that are not observable using traditional bulk RNAseq methods. Taken together, the study gives a previously unavailable view of disease progression in ALS and also provides a general experimental framework for understanding disease in complex tissue. Access the suite of interactive data exploration and visualization tools that accompany the preprint directly at: als-st.nygenome.org.
Connecting with ALS patients and their caregivers is an often heartbreaking yet critically essential element of the work of the CGND and its ALS Consortium members. On June 23, Dr. Phatnani took part, with Dr. Bruijn and Matthew Harms, MD, Associate Professor of Neurology at Columbia University College of Physicians and Surgeons, as fellow panelists, in an “Ask the Experts” Patient Symposium panel held at the NYGC and organized by The ALS Association Greater New York Chapter, which also sponsored this year’s ALS Consortium Meeting. In addition to sharing information and answering questions at this event, Dr. Phatnani also recently gave a tour of her lab, at the request of Project ALS, which also provides funding for her research, to a group of mothers who had lost children to ALS and found each other on Facebook. She was also featured in the recent documentary “Living with ALS.” Watch the documentary here.
Dr. Marcin Imielinski Will Explore Melanoma’s “Telomere Crisis” in Award-Winning MRA Project
It is a critical marker of cancer evolution and development: the loss of the protective telomeric elements at the ends of chromosomes, causing chromosome ends to stick together, creating an unstable genome. This telomeric element of DNA withers away during the many cell divisions involved in cancer development.
In April, NYGC Core Faculty Member Marcin Imielinski, MD, PhD, and collaborators from The Rockefeller University and Memorial Sloan Kettering Cancer Center were recipients of the Black Family-Melanoma Research Alliance (MRA) Team Science Award, for a project specifically focused on this phenomenon, entitled “Telomere crisis in acral melanoma: Diagnostic and prognostic potentials.” Unlike cutaneous melanoma, which is caused by UV damage to DNA, the origin of acral melanoma, which usually appears as brown or black discoloration in palms and soles or beneath the nails and can be deadly if it spread to other organs when left untreated, is poorly understood. Previous studies have suggested that acral melanoma genomes show evidence of the type of changes known to result from telomere crisis, and the team will use its expertise in studying telomere function, telomere crisis, and genomic alteration, to determine whether and how telomere crisis shapes the acral melanoma genome, with the goal to develop tools to predict the progression and evolution of the cancer and treatment response of individual acral melanomas. Dr. Imielinski, who holds joint appointment as Assistant Professor of Computational Genomics and Assistant Professor of Pathology & Laboratory Medicine, Weill Cornell Medicine, and Rockefeller’s Titia de Lange, Ph.D., are principal investigators working with Memorial Sloan Kettering Cancer Center’s John Maciejowski, PhD, on this project.
As part of the Imielinski Lab’s ongoing work with the Pan-Cancer Analysis of Whole Genomes (PCAWG) initiative, an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes, Dr. Imielinski is co-author of Portraits of genetic intra-tumour heterogeneity and subclonal selection across cancer types, posted as a preprint on bioRxiv in July. The study delves into the role of intra-tumor heterogeneity (ITH) in cancer evolution, specifically how tumor cells can be subtly or dramatically different even within the same tumor from the same patient, which creates challenges for clinicians to characterize patients’ cancer and guide their treatment. The team’s work provides an unprecedented pan-cancer resource of extensively annotated detail that lays a foundation for future cancer genomic studies.
Other recent Imielinski Lab collaborations include work on genomic tools SvABA: genome-wide detection of structural variants and indels by local assembly, published in Genome Research in April, and Pore-C: using nanopore reads to delineate long-range interactions between genomic loci in the human genome, a collaboration with Oxford Nanopore Technologies.
Dr. Dan Landau Receives Inaugural ASPIRE Award to Accelerate “Liquid Biopsy” Cancer Detection
Improving liquid biopsy, the emerging science which allows for early detection of cancer through the measurement of tumor DNA in a patient’s blood, is a key focus of the research team led by NYGC Core Faculty Member Dan Landau, MD, PhD, who holds a joint appointment as Assistant Professor of Medicine in the Division of Hematology and Medical Oncology and the Department of Physiology and Biophysics at Weill Cornell Medicine. Increasingly, a liquid biopsy approach is being used as an alternate diagnostic tool to patient imaging scans, which can be inconclusive, or invasive tumor biopsies.
In June, in support of the lab’s work in this area, The Mark Foundation for Cancer Research selected Dr. Landau as the inaugural recipient of its new ASPIRE (Accelerating Scientific Platforms and Innovative Research) Award. The lab’s award-winning project is focused on developing a more highly sensitive platform for liquid biopsy, seeking to overcome current barriers to accurately diagnosing cancer when tumors are very small and only minute amounts of tumor DNA are available in the quantities of blood that can be taken from a patient. Read more about the award here. Also in July, the Landau Lab received a Lung Cancer Discovery Award from the American Lung Association, providing $100,000 per year for up to two years, to support its work.
In May, Dr. Landau was one of seven winners of a 2018 Pershing Square Sohn Prize for Young Investigators in Cancer Research, part of the Pershing Square Sohn Cancer Research Alliance’s efforts to further New York City’s growth as a biomedical research hub, with each awardee receiving $200,000 per year for up to three years. Here, the lab’s award-winning project is focused on studying the non-genetic mechanisms driving cancer evolution, which remains an underexplored yet emerging theme across the field of oncology. Using novel molecular and computational tools developed in the lab to analyze DNA, epigenetic information and gene expression in single cells, Dr. Landau’s team of biologists, physician scientists, data analysts and engineers will generate experimental models and measurements in patient leukemia samples, seeking to enable precision customization of anti-cancer therapy to prevent non-genetic evolution to treatment resistance.
In late March, Dr. Landau, a 2016 recipient of a Stand Up to Cancer (SU2C) Innovative Research Grant, and Columbia University’s Raul Rabadan, PhD, currently a principal investigator on the SU2C-National Science Foundation’s Drug Combination Convergence Team, were winners of a 2018 SU2C Philip A. Sharp Innovation in Collaboration Award. He will work with Dr. Rabadan on a project, supported by SU2C’s $250,000 grant, entitled “Cupid-seq—high throughput transcriptomic spatial mapping of immune-tumor interactions in the micro-environment.” The investigators will devise a novel sequencing technique and computational method for better understanding immune recognition mechanism in glioblastoma.
Dr. Tuuli Lappalainen Receives Leena Peltonen Prize for Excellence in Human Genetics
On June 16, in Milan, Italy, Tuuli Lappalainen, PhD, Core Faculty Member, NYGC, and Assistant Professor in the Department of Systems Biology at Columbia University, was presented with the Leena Peltonen Prize for Excellence in Human Genetics at the 52nd Annual European Society of Human Genetics (ESHG) meeting, the largest human genetics conference in Europe. Dr.Lappalainen is the third-ever recipient and first-ever Finnish genomic researcher to receive this prize, an award established in 2010 to honor the late Leena Peltonen, one of Finland’s most renowned scientists.
“Among all the many excellent candidates, Tuuli Lappalainen clearly stood out for both her prestigious scientific talents and her extraordinary contribution within large ‘team science’ projects,” noted Professor Mark McCarthy from the University of Oxford, chair of the selection committee, in a news story about the event.
Dr. Lappalainen and her lab team are currently involved in an array of team science collaborative research, including ongoing work with the Genotype-Tissue Expression (GTEx) Consortium to study patterns and mechanisms of gene regulation across tissues and genetic regulatory variants that are active in specific cell types. On May 8, the lab served as host for a workshop for a GTEx analysis group at the NYGC, and is now working on a number of papers based on the final GTEx data release.
The National Heart, Lung, and Blood Institute (NHLBI) also recently awarded R01 funding, with Dr. Lappalainen as principal investigator, for a proposed two-year project to integrate large biological datasets to improve interpretation of genetic risk variants in lung disease. The work is part of NHLBI’s Multi-Ethnic Study of Atherosclerosis (MESA) and Trans-Omics for Precision Medicine (TOPMed) initiatives and part of the lab’s collaborative research activities with Graham Barr, MD, PhD, Columbia University Medical Center.
In March, Dr.Lappalainen and Harmen Bussemaker, PhD, a fellow faculty member at Columbia and a leader in the field of motif discovery and quantitative prediction of protein-DNA interaction, were recipients of an inaugural Roy and Diana Vagelos Precision Medicine Pilot Award, new grant funding within Columbia’s Precision Medicine Initiative. One of three winning proposals awarded out of a pool of 56 applications, their collaboration will bridge quantitative genetics and mechanistic biology to obtain a mechanistic understanding of regulatory effects of genetic variants in humans. Read more about their collaboration here.
The Lappalainen Lab’s latest preprint is RecNW: A fast pairwise aligner for targeted sequencing, posted to bioRxiv in July, outlining new open-source implementation of the Needleman-Wunsch algorithm, which allows much faster alignment of targeted sequencing data, on average more than four times faster than comparable software. Senior co-authors on the study are Pejman Mohammadi, PhD, a former lab team member and now an Assistant Professor at the Scripps Translational Science Institute, San Diego, and Nicholas Tatonetti, PhD, Assistant Professor of Computational Biology at Columbia University. Alexandre Yahi, a rotation graduate student in the Lappalainen Lab in 2016 and now working in the Tatonetti Lab, is the first author. Dr. Lappalainen also contributed to another recent publication, led by Zeynep Coban-Akdemir from James Lupski’s lab at the Baylor College of Medicine, where data that Dr. Lappalainen previously studied was reanalyzed to understand dominant disease-causing mutations.
In August, the Lappalainen Lab’s paper Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk, was published in Nature Genetics. The study, led by Dr. Lappalainen alongside post-doctoral research fellow Stephane Castel, PhD, offers insights into modified penetrance, in which genetic variants that regulate gene activity modify the disease risk caused by protein-coding gene variants. The researchers leveraged large genomic datasets and CRISPR to link modified penetrance to specific diseases at the genome-wide level, which has implications for future prediction of the severity of serious diseases such as cancer and autism spectrum disorder. For the NYGC press release and highlights of media coverage of this study, click here.
Dr. Neville Sanjana Receives AAAS Award, $1M DARPA Grant In Recognition of CRISPR-Focused Research
A genome-wide net to catch and understand cancer is the title of the prize-winning essay written by NYGC Core Faculty Member Neville Sanjana, PhD, describing his research focused on pioneering gene-editing technology CRISPR, and featured as the August 8 cover story of Science Translational Medicine.
The essay was selected by the American Association for the Advancement of Science (AAAS) and the AAAS journal Science Translational Medicine for its prestigious 2018 AAAS Martin and Rose Wachtel Cancer Research Award, which recognizes early-career investigators who have performed outstanding work in the field of cancer research. In addition to his essay being published in Science Translational Medicine, Dr. Sanjana, one of only two recipients honored this year, gave a public lecture on the essay at the National Institute of Health’s Lipsett Amphitheater on August 10.
In July, Dr. Sanjana, who holds joint appointments as Assistant Professor of Biology, New York University (NYU) and Assistant Professor of Neuroscience and Physiology, NYU School of Medicine, was the recipient of a 2018 Young Faculty Award from the Defense Advanced Research Projects Agency (DARPA). The award, a grant of $1M over three years, will fund work to accelerate development of new methods for precision gene editing to repair disease-causing mutations. “Over the past five years, CRISPR systems have made it relatively easy to knock-out or block expression of certain genes in human cells,” noted Dr. Sanjana in the NYU press release about the award. “However, it has been more challenging to perform precise gene surgery to correct DNA mutations in these genes — a significant obstacle as many serious genetic diseases are caused by small mutations.”
The Sanjana Lab’s recent publications include Dr. Sanjana’s joint lead authorship on a study on rare variants in the autism spectrum disorder known as Angelman Syndrome, published by the American Journal of Medical Genetics in April.
Dr. Sanjana also gave recent talks on his lab’s research to the medical/science community at the European Society for Human Genetics and the National Human Genome Research Institute’s Advanced Genomic Technology Development meetings in June; the University of Pennsylvania’s Institute for Biomedical Informatics Genomics and Computational Biology Retreat (as keynote speaker) in May; St. John’s University’s Department of Biological Sciences and Yale University’s Department of Genetics in April, and the Mount Sinai School of Medicine Child Health Research Series Seminar and Duke University Center for Applied Genomics and Precision Medicine Seminar in March.
Dr. Rahul Satija Publishes New Findings in Immune and Neuronal Development
This spring, Nature published a study by NYGC Core Faculty Member Rahul Satija, PhD, and his lab, working in a close collaboration with NYU Medical School, in which the researchers sequenced 65,000 single cells from the developing mouse brain in order to understand how newly born interneurons decide between different fates. The team found that fate specification occurs even in the early embryo, and identifies specific genes involved in the process – many of which have been linked to neuropsychiatric and neurodevelopment disorders. Read more about the study, and the fascinating cells which Ramon y Cajal deemed “butterflies of the soul,” here.
Also this spring, a study of the Satija Lab’s new algorithm for single cell data integration was published in Nature Biotechnology. By applying analytical patterns specialized at aligning image datasets to sequencing data, the lab found that shared cell types could be effectively aligned across single cell experiments. The method can be used to correct for batch effects across labs, compare drug-treated and control samples, or even to identify shared cell types across species. The method is freely available as part of the lab’s Seurat software package, and has been downloaded 50,000 times in the past year.
The lab also had a study published in Molecular Systems Biology that was focused on understanding the gene expression programs hematopoietic stem cells switch on when transitioning through development. Lab researchers found that early progenitors simultaneously express genes that are associated with multiple outcomes, a conflict that is resolved later in differentiation, and also identified novel markers of cell state and potential in human cord blood.
In June, lab’s collaborative study with Claude Desplan’s lab at NYU was published in Cell and presents an atlas of 52 transcriptomic subtypes in the fruit fly optic lobe. Jan Slabbaert, PhD, Postdoctoral Research Fellow, was awarded a fellowship from the Belgian American Educational Foundation to build upon these results and understand how different cell types emerge during fly development.
Lastly, the lab celebrated a grant from the Chan Zuckerberg Initiative to develop computational tools for the Human Cell Atlas. The lab is excited to pursue new projects focused on the integration of cutting-edge imaging technologies with single-cell sequencing.
Publications & Preprints
NYGC faculty and staff continue to advance genomic science with research studies published in high-impact scientific journals. For an up-to-date listing of the NYGC publications and preprints by NYGC faculty and staff, visit the Publications section of the NYGC website.
Education & Outreach
NYGC Hosts Inaugural Polyethnic-1000 Summer Retreat and Second NCBI Hackathon
On August 8, NYGC’s Genome Center Cancer Group (GCCG) hosted a summer retreat to discuss Polyethnic-1000, the new collaborative effort organized by GCCG to advance cancer genomics and its practice in clinical care by leveraging the City’s large and ethnically diverse population. The vision of Polyethnic-1000 is to deepen understanding of the contributions that ethnicities make to the incidence and behavior of cancers, thereby improving outcomes especially for patients who currently lack access to the most recent advances in medical science. The retreat introduced GCCG’s plans for the three phases of this important study to both new participants and existing NYGC partner institutions.
The Polyethnic-1000 steering committee includes Drs. Harold Varmus, Weill Cornell Medicine & NYGC; Charles Sawyers, Memorial Sloan Kettering Cancer Center; David Tuveson and Fieke Froeling, Cold Spring Harbor Laboratory; as well as NYGC’s Nicolas Robine, PhD, Assistant Director, Computational Biology, Mike Zody, PhD, Senior Director, Computational Biology, Dayna Oschwald, Chief of Staff, Office of the Scientific Director & CEO, and Ben Hubert, Scientific Collaboration Manager. Guest speakers at the retreat were Laura Martello-Rooney, SUNY Downstate; Peter Kingham, Memorial Sloan Kettering Cancer Center; David Beer, University of Michigan; Jianjiong Gao, Memorial Sloan Kettering Cancer Center; Timothy Rebbeck, Dana-Farber Cancer Institute; and Vijai Joseph, Memorial Sloan Kettering Cancer Center.
More information about Polyethnic-1000 is also available on the project’s newly launched website.
From August 6 to August 8, the NYGC also hosted its second Genomics Hackathon in collaboration with the National Center for Biotechnology Information. Six teams comprised of researchers, postdocs and students spent three days building pipelines and tools to analyze large datasets, addressing challenging scientific problems related to genomics and general data science. Projects at this year’s Hackathon focused on building a tool to find RNAseq and epigenomics for biosamples with underlying structural variants, building a database of DNA repair sites and mechanisms, and building a web framework for visualizing and interacting with drug safety data, among other subjects. Lead Bioinformatics Scientist Giuseppe Narzisi, PhD, served as NYGC scientist host for this year’s Hackathon, with Toby Bloom, PhD, Senior Director, Strategic Genomic Analytics, and Nicolas Robine, PhD, Assistant Director, Computational Biology, also giving presentations to the group.
Ongoing Education & Outreach Events
The NYGC continues to host New York Cancer Genomics Research Network Meetings and Five Points Lectures for the scientific community and Evening Talks for the general public.
For more on all upcoming events, visit the Events section of the NYGC website.
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