Aberrant patterns in the epigenomic landscape have been closely associated with cancer.
Deregulation of histone modifications silences tumor-suppressor genes, triggers genetic
changes via aberrant DNA repair/replication, and contributes to tumor heterogeneity. Chromatin
immunoprecipitation (ChIP) assay is the technique of choice for examining epigenetic
mechanisms in vivo such as histone modifications. However, the technique in its conventional
form suffers from serious limitations. The prevailing ChIP-seq protocol requires 107 cells per
test, involves extensive manual handling of the samples, and takes 3-4 days to generate a
sequencing library. The requirement of a large sample amount practically prevents the use of
ChIP-seq on samples from scarce sources such as animal models and patients. We recently
demonstrated a microfluidic technology (microfluidic-oscillatory-washing-based ChIP-seq or
MOWChIP-seq) for profiling genome-wide histone modifications using as few as 100 cells. In
this R33 project, we will develop the next-generation MOWChIP-seq technology by facilitating
high throughput, improving the level of integration, and further validating the technology via
testing mouse and human samples. The development will fully validate the use of MOWChIP-
seq for high-throughput epigenomic profiling of a large number of samples in clinical research
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