Melissa Gymrek, PhD, Speaks This Friday, Feb. 26: “Dissecting the Contribution of Complex Genetic Variation to Human Traits”

Computer Science and Engineering Colloquium Talk / Winter 2016

Melissa Gymrek, PhD
Massachusetts General Hospital and the Broad Institute

Friday, February 26, 2016
12 – 1 p.m.

Computer Science and Engineering Building EBU-3B, Room CSE 1202

Title: Dissecting the Contribution of Complex Genetic Variation to Human Traits

Abstract:
Recent studies have made substantial progress in identifying genetic variants associated with disease and molecular phenotypes in humans. However, these studies have primarily focused on single nucleotide polymorphisms (SNPs), ignoring more complex variants that have been shown to play important functional roles. Here, I focus on short tandem repeats (STRs), one of the most polymorphic and abundant classes of genetic variation. I will first present lobSTR, a novel algorithm for genotyping STRs from whole-genome sequencing datasets. Next, I will describe insights into population-wide trends of STR variation revealed by applying lobSTR to thousands of sequencing datasets to generate the largest and highest-quality STR catalog to date. I will then show how we used this catalog to conduct a genome-wide analysis of the contribution of STRs to gene expression in humans. This survey revealed that STRs explain 10-15% of the heritability of expression mediated by all common cis variants and potentially play an important role in clinically relevant conditions. Finally, I will discuss preliminary analyses incorporating functional genomics data with high-quality complex variant genotypes to predict and validate the function of non-coding variants driving common human diseases. Altogether, these results highlight the putative phenotypic contribution of complex variants and the opportunity for a wealth of genetic discoveries to be gained by expanding analyses to less-understood regions of the genome.

Bio:
I am currently a post-doctoral fellow at Massachusetts General Hospital and the Broad Institute. I recently received my PhD in Bioinformatics and Integrative Genomics from the Harvard/MIT Division of Health Sciences and Technology under the supervision of Yaniv Erlich and Mark Daly. Prior to my PhD, I received my B.S. in Computer Science and Mathematics at MIT.

My major research interest is to understand complex genetic variants that underlie phenotypic changes, ultimately leading to human disease. My recent work focuses on repetitive DNA variants known as short tandem repeats (STRs) as a model for complex variation. I develop computational methods for analyzing and visualizing complex variation from large-scale sequencing data. These tools allow us for the first time to answer many questions regarding STRs and other variant types, including their contribution to complex human phenotypes. In future work, I aim to build on my experience dissecting challenging regions of the genome to develop and test predictive models of the regulatory effects of complex sequence variation.

Faculty Host:
Vineet Bafna, PhD
Professor of Computer Science and Engineering
Jacobs School of Engineering
UC San Diego
vbafna@ucsd.edu

GenomeSpace “Recipes” Help Biologists Interpret Genomic Data

Data analysis platform will enlist the user community to streamline use of multiple bioinformatics tools —

Many biomedical researchers are striving to make sense of the flood of data that has followed recent advances in genomic sequencing technologies. In particular, researchers are often limited by the challenge of getting multiple bioinformatics tools to “talk” to one another. To help address this need, researchers at University of California, San Diego School of Medicine, in collaboration with labs at the Broad Institute of MIT and Harvard, Stanford University, Weizmann Institute and Pennsylvania State University, developed GenomeSpace, a cloud-based, biologist-friendly platform that connects more than 20 bioinformatics software packages and resources for genomic data analysis.

The team is now developing and crowdsourcing “recipes” — step-by-step workflows — to better enable non-programming researchers to interpret their genomic data … Read the full story from the UC San Diego Newsroom


Dr. Jill Mesirov

Dr. Jill Mesirov

Jill Mesirov, PhD, is senior investigator on the GenomeSpace project. Dr. Mesirov joined UC San Diego in 2015 as Associate Vice Chancellor for Computational Health Sciences and Professor of Medicine in the Division of Medical Genetics.

Trey Ideker, PhD, Professor of Medicine, is a coauthor.

The article citation: Qu K, Garamszegi S, Wu F, et al. Nature Methods. 2016 Jan 18. doi: 10.1038/nmeth.3732.

Spotting the Earliest Signs of Type 1 Diabetic Kidney Disease

JDRF network grant to fund study to find new types of diagnostic markers —

In an effort to pinpoint the earliest signs of diabetic kidney disease, researchers at University of California, San Diego School of Medicine are leading a multi-institutional international effort dedicated to finding a new breed of disease indicators.

The study, funded by a $2.5 million JDRF (formerly known as the Juvenile Diabetes Research Foundation) grant, will tap the potential of three emerging “omics” sciences to discover new ways to determine which patients are most likely to develop diabetic kidney disease. Samples from more than 2,000 type 1 diabetes patients, collected over a period of years by several medical centers around the world, will be used in the analyses. …Read the full story from the UC San Diego Newsroom


Kumar Sharma, MD, FAHAPrincipal investigator of the study is Kumar Sharma, MD, FAHA, Professor of Medicine in the Division of Nephrology. He directs the Center for Renal Translational Medicine and the Institute of Metabolomic Medicine in UC San Diego School of Medicine.

Jill P. Mesirov Appointed Associate Vice Chancellor for Computational Health Sciences

UC San Diego School of Medicine recruits world leader in computational biology —

Leading computational biologist Jill P. Mesirov, PhD, has been appointed associate vice chancellor for computational health sciences and professor of medicine at University of California, San Diego School of Medicine and Moores Cancer Center. Mesirov most recently served as associate director and chief informatics officer at the Broad Institute of MIT and Harvard, where she directed the Computational Biology and Bioinformatics Program. … Read the full story from the UC San Diego Newsroom


Dr. Mesirov joins the Department of Medicine as a professor in the Division of Medical Genetics.

Division of Regenerative Medicine Holds First Research Symposium

Catriona H. M. Jamieson, MD, PhD

Dr. Catriona Jamieson

On Friday, January 30, the Division of Regenerative Medicine presented its inaugural symposium on novel research and technologies in regenerative medicine.

The meeting featured scientific presentations by world-renowned academic investigators and industry leaders as well as a discussion panel including keynote speakers Dr. Hans Clevers, Dr. Derrick Rossi, Dr. Carl June and Dr. Wolfgang Dillmann.

Division Chief Catriona Jamieson, MD, PhD, presented the mission and milestones of the new Division of Regenerative Medicine after introductions from UC San Diego Chancellor Pradeep Khosla; Vice Chancellor Health Sciences and Dean of UC San Diego School of Medicine Dr. David Brenner; and Chief Executive Officer of UC San Diego Health System and Associate Vice Chancellor of UC San Diego Health Sciences Paul Viviano.

UC San Diego Moores Cancer Center

UC San Diego Moores Cancer Center

Catriona Jamieson, MD, PhD, is associate professor in the Division of Hematology-Oncology, deputy director of the Sanford Stem Cell Clinical Center, chief of the Division of Regenerative Medicine and director of stem cell research at the Moores Cancer Center.

UC San Diego, UC San Francisco Launch New Cancer Cell Mapping Initiative

Researchers from the University of California, San Diego School of Medicine and University of California, San Francisco, with support from a diverse team of collaborators, have launched an ambitious new project – dubbed the Cancer Cell Map Initiative or CCMI – to determine how all of the components of a cancer cell interact.

“We’re going to draw the complete wiring diagram of a cancer cell,” said Nevan Krogan, PhD, director of the UC San Francisco division of QB3, a life science research institute and accelerator, an investigator at Gladstone Institutes and co-director of CCMI with Trey Ideker, PhD, chief of medical genetics in the UC San Diego Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics. … Read the full story from the UC San Diego Newsroom

 


Trey Ideker, PhD

Trey Ideker, PhD

Trey Ideker, PhD, is professor of bioengineering and professor of medicine in the Division of Medical Genetics. He was recently named a fellow of the American Association for the Advancement of Science (AAAS).

Dr. Ideker’s Laboratory Website

Century-Old Drug Reverses Autism-like Symptoms in Fragile X Mouse Model

Autism spectrum disorders (ASD) affect 1 to 2 percent of children in the United States. Hundreds of genetic and environmental factors have been shown to increase the risk of ASD. Researchers at UC San Diego School of Medicine previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice.

Now, a new study published in this week’s online issue of Molecular Autism, suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice. … Read the full story from the UC San Diego Newsroom


Chief investigator of the study is Robert Naviaux, MD, PhD, professor of medicine in the Division of Medical Genetics and professor in the departments of pediatrics and pathology.

Dr. Naviaux is co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego.

Read the abstract of the article in Molecular Autism

More about research in the Naviaux laboratory

Grant Gives New Breath to Patients Suffering from Severe Pulmonary Hypertension

Nearly $8 million grant helps launch a nationwide patient registry to improve CTEPH practices

Imagine trying to take a deep breath, but feeling like you’re sucking air through a straw. That’s how some patients with chronic thromboembolic pulmonary hypertension (CTEPH) describe living with the condition, which is estimated to affect several thousand Americans yearly but is commonly misdiagnosed. UC San Diego Health System is a world leader in CTEPH, and now with a $7.6 million grant, has helped launch the first national CTEPH registry to improve best practices and patient care. … Read the full story from the UC San Diego Newsroom


Dr. Kim KerrPrincipal Investigator of the project is Kim Kerr, MD, professor of clinical medicine in the Division of Pulmonary and Critical Care Medicine. She directs the Medical Intensive Care Unit at UC San Diego Health System’s Thornton Hospital in La Jolla.

Dr. Michael MadaniCardiac surgeon Michael Madani, MD, co-investigator, is chief of cardiothoracic surgery and director of UC San Diego Sulpizio Cardiovascular Center – Surgery.

Big Data Sharing for Better Health

Researchers at University of California, San Diego School of Medicine have been awarded a $9.2 million grant to help modernize and transform how researchers share, use, find and cite biomedical datasets.

The 3-year project, in collaboration with The University of Texas Health Science Center at Houston, is part of a federal initiative to increase the utility of biomedical research data, launched this week by the National Institutes of Health (NIH) through its Big Data to Knowledge (BD2K) program. … Read the full story from the UC San Diego Newsroom


Dr. Lucila Ohno-MachadoLucila Ohno-Machado, MD, PhD, is lead investigator on the Biomedical and healthCAre Data Discovery and Indexing Ecosystem (BioCADDIE) project.

Dr. Ohno-Machado, professor of medicine, is founding chief of the Division of Biomedical Informatics.

Read the BioCADDIE project description on the NIH RePORTER

Tumor Suppressor Mutations Alone Don’t Explain Deadly Cancer

Biomarker for head and neck cancers identified

Although mutations in a gene dubbed “the guardian of the genome” are widely recognized as being associated with more aggressive forms of cancer, researchers at the University of California, San Diego School of Medicine have found evidence suggesting that the deleterious health effects of the mutated gene may in large part be due to other genetic abnormalities, at least in squamous cell head and neck cancers. … Read the full story from the UCSD Newsroom


Trey Ideker, PhD

Trey Ideker, PhD, professor and chief in the Division of Medical Genetics and professor of bioengineering, is one of the study’s co-senior authors.

Other Department of Medicine faculty authors include Hannah Carter, PhD, assistant professor; and Scott M. Lippman, MD, professor of medicine and director of the UC San Diego Moores Cancer Center.

Hannah Carter, PhD Dr. Scott M. Lippman