The Gymrek Lab is located at the University of California San Diego. We are part of the Department of Pediatric's Division of Genetics and are also affiliated with the Department of Medicine and Department of Computer Science and Engineering. We are a member of the Bioinformatics and Systems Biology and Biomedical Sciences graduate programs at UCSD.

What do we do?

Our overall goal is to understand genetic variants that underlie human disease and how their effects vary across different populations. We are a multidisciplinary lab and include both computational and wet lab biologists. We are particularly interested in repetitive DNA variants known as tandem repeats (TRs). Major research areas include (1) developing computational tools for analyzing TR variation in biobank-scale genomic datasets, (2) identifying TRs contributing to both rare and complex traits, (3) studying mutation and selection processes at TRs within and across species, (4) understanding how the effects of TRs and other genetic variants differ across human populations, and (5) using high-throughput experimental techniques to study the impacts of TR and other variants on molecular and cellcular phenotypes in healthy and disease states. Read more about our work on our research page!.

Featured publications

Polymorphic short tandem repeats make widespread contributions to blood and serum traits. Jonathan Margoliash, Shai Fuchs, Yang Li, Xuan Zhang, Arya Massarat, Alon Goren, Melissa Gymrek. (Cell Genomics 2023) [DOI] [Accompanying perspective]

We performed the first genome-wide association study (GWAS) based on STRs. This study analyzed the contribution of STRs to 44 blood and serum biomarkers in the UK Biobank. Using two fine-mapping methods, we identified 119 candidate causal STR-trait associations and estimate that STRs account for 5.2%–7.6% of causal variants identifiable from GWASs for these traits. Summary statistics are available here.

In this study, we develop an ensemble-based genotyping method (EnsembleTR) and characterize ~1.7 million tandem repeats across 3,550 samples from 1000 Genomes and H3Africa projects.

A deep population reference panel of tandem repeat variation. Helyaneh Ziaei Jam, Yang Li, Ross DeVito, Nima Mousavi, Nichole Ma, Ibra Lujumba, Yagoub Adam, Mikhail Maksimov, Bonnie Huang, Egor Dolzhenko, Yunjiang Qiu, Fredrick Elishama Kakembo, Habi Joseph, Blessing Onyido, Jumoke Adeyemi, Mehrdad Bakhtiari, Jonghun Park, Sara Javadzadeh, Daudi Jjingo, Ezekiel Adebiyi, Vineet Bafna & Melissa Gymrek. (Nature Communications 2023). [DOI]

Patterns of de novo tandem repeat mutations and their role in autism. Ileena Mitra, Bonnie Huang, Nima Mousavi, Nichole Ma, Michael Lamkin, Richard Yanicky, Sharona Shleizer-Burko, Kirk E. Lohmueller, Melissa Gymrek. (Nature 2021). [pubmed]

In this study we develop methods to identify (MonSTR) and prioritize (SISTR) de novo mutations at tandem repeats in WGS data, and then characterize patterns of TR mutations in the general healthy population, as well as, in individuals affected by autism. This work was a fun collaboration with the Lohmueller Lab from UCLA!

We designed a machine learning framework, AgentBind, to identify and interpret sequence features that are most important for transcription factor (TF) binding. Unlike most previous works studying binding motifs, our work focuses on the sequence context in the vicinity of motifs and studies its role in TF binding.

Deep neural networks identify sequence context features predictive of transcription factor binding. An Zheng, Michael Lamkin, Hanqing Zhao, Cynthia Wu, Hao Su & Melissa Gymrek (Nature Machine Intelligence 2021). [DOI]

TRTools: a toolkit for genome-wide analysis of tandem repeats. Nima Mousavi, Jonathan Margoliash, Neha Pusarla, Shubham Saini, Richard Yanicky, Melissa Gymrek (Bioinformatics 2020). [pubmed]

This manuscript describes TRTools, a suite of tools for analysis of tandem repeat variation. It offers command-line tools for filtering, merging, and performing QC on VCFs containing tandem repeat genotypes. TRTools can also be imported as a Python library into custom scripts.

In this study we demonstrate that variation at thousands of tandem repeats across the genome have an impact on expression of nearby genes across many human tissue types. Effects are strongest for GC-rich STRs near transcription start sites. This work was a fun collaboration with the Goren Lab next door!

The impact of short tandem repeat variation on gene expression. Stephanie Feupe Fotsing, Jonathan Margoliash, Catherine Wang, Shubham Saini, Sharona Shleizer-Burko, Alon Goren, Melissa Gymrek (Nature Genetics 2019). [pubmed]

Profiling the genome-wide landscape of tandem repeat expansions. Nima Mousavi, Sharona Shleizer-Burko, Richard Yanicky, Melissa Gymrek (Nucleic Acids Research 2019). [pubmed]

GangSTR is a tool for profiling tandem repeat variation from next-generation sequencing datasets. It takes as input aligned reads (BAMs) for one or more samples and outputs VCF files with estimated repeated lengths at a reference set of TRs. GangSTR can capture variation both at short and expanded TRs.

In this study we generate a SNP-STR haplotype panel by phasing STRs onto SNP haplotypes. This panel can be used to impute STR genotypes into datasets for which they cannot be directly genotyped (e.g. SNP genotyping array data commonly used for GWAS studies). We found that the majority of STRs can be accurately imputed, with a mean genome-wide imputation accuracy 97% for European samples.

A reference haplotype panel for genome-wide imputation of short tandem repeats. Shubham Saini, Ileena Mitra, Nima Mousavi, Stephanie Feupe Fotsing, Melissa Gymrek (Nature Communications 2018). [pubmed]