EP 228: What genomes reveal about Epstein–Barr virus and human disease with Ryan Dhindsa and Caleb Lareau

Feb 26, 2026

Caleb Lareau, computational genomics PI studying the human virome and sequencing methods, and Ryan Dhindsa, population geneticist focused on rare variants and disease mechanisms, discuss extracting Epstein–Barr virus signals from human genomes. They cover rescuing viral reads from WGS, validating EBV persistence in UK Biobank, links to autoimmune conditions, extending methods to the broader virome, and design needs for diverse population genomics.

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ANECDOTE

Twitter DM Sparked Major EBV Collaboration

Caleb Lareau initiated a collaboration with Ryan Dhindsa after a Twitter DM about related single-cell and population genetics observations.
Their informal DM blossomed into a multi-year partnership that produced the EBV persistence study using biobank data.

INSIGHT

Rescuing Viral Signal From Unmapped Reads

Unmapped reads from human whole-genome sequencing can be remapped to viral genomes to create molecular traits like EBV latency.
Caleb and Ryan validated their pipeline by correlating EBV-mapped reads with UK Biobank serology and other omics to confirm a true latent signal.

INSIGHT

Mapping Quality Hid The True EBV Signal

Naive counting of EBV-aligned reads gave a null correlation with serology due to repetitive elements and mapping artifacts.
Cleaning repetitive 'junk' alignments and improving mapping quality revealed the true EBV persistence signal.

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This week on The Genetics Podcast, Patrick is joined by Dr. Ryan Dhindsa, Assistant Professor at the Baylor College of Medicine and PI at Texas Children’s Hospital, and Dr. Caleb Lareau, PI at Memorial Sloan Kettering Cancer Center and Assistant Professor of Computational Biology and Medicine at Weill Cornell Medicine. They discuss how a Twitter DM sparked a multi-year collaboration to extract Epstein–Barr virus signals from large-scale human genomic datasets, how measuring viral persistence in UK Biobank data reveals insights into autoimmune disease risk and host genetic control, and what this work means for understanding the long-term impact of chronic viral infections on human health.

Show Notes:

0:00 Intro to The Genetics Podcast

00:59 Welcome to Ryan and Caleb

01:58 How a Twitter DM led to a long-term collaboration

03:10 Rescuing Epstein–Barr virus (EBV) sequences from human whole genome data

04:45 Quantifying EBV persistence in UK Biobank, validating the signal, and uncovering links to autoimmune disease

12:00 Computational virology, chronic viral effects on human disease, and extending the approach to the broader human virome

16:59 Design considerations for population genomics programs to better capture chronic viral effects on human disease

21:30 Genetic, viral strain, and environmental factors that shape EBV persistence and immune control

26:09 Future directions for EBV research and expanding beyond European ancestry cohorts

29:46 Focus areas of Ryan’s research including rare variant genetics, neurological disease mechanisms, and pediatric population genomics

33:49 Focus areas of Caleb’s research including the human virome and expanding sequencing technologies to detect uncharacterized nucleic acids

37:03 Where genomic “dark matter” may underlie unexplained cancer and severe disease

38:46 Gaps in non-coding variant interpretation and incomplete penetrance in unsolved genetic disease

42:01 Closing remarks

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