Research in the Sheffield lab

Nathan Sheffield, PhD
We develop and apply computational methods
to organize, analyze, and understand large epigenomic data.



Gene regulation


High-performance computing
Machine learning
Data science

Biological motivation

Every cell in your body has the same genome*...

Yet your cells are diverse

Biological motivation

How can a single set of instructions
give rise to such a complex multicellular being?

Biological motivation

Through the process of differentiation,
cells assume individual functions and roles

Biological motivation

But when differentiation goes awry, disease may result

Biological motivation

Each cell-type folds DNA differently,
thereby using a different subset and
providing a molecular signature of its behavior

DNA folding can be measured by sequencing DNA

But huge, diverse datasets lead to computational challenges.

Research highlights

Defining cell type from chromatin accessibility

Sheffield et al. (2013). Genome Research.

Epigenetic heterogeneity in pediatric cancer

Sheffield et al. (2017). Nature Medicine.

Inferring regulatory activity from DNA methylation

Lawson et al. (2018). Bioinformatics.

Future projects

  • Connecting the genome to the epigenome
  • Acute Myeloid Leukemia epigenomics
  • Neuro-immuno-epigenomics
  • Standardizing metadata for big biomedical data analysis
Thanks for listening!

nsheff · ·
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