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Abstract:
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The cell is the basic unit of life. In 1855, Rudolf Virchow offered "chromatin" as a name for the material that allows cells to produce other cells. Pathology of the organism, he wrote, arose from pathology of the cells; as evidence, Virchow presented misshapen chromosomes in cells from leukemia patients. A century passed before Nowell, Hungerford, and Rowley demonstrated how pathology of the chromosomes led to life-threatening disease. Soon after, Don and Ada Olins revealed how chromatin winds and unwinds to expose DNA for transcription.
More recently, a flood of single-cell methods has characterized cells in unprecedented scope, via both imaging and sequencing. Adrift in a sea of single-cell data, Virchow's generative model provides a useful anchor.
Our group has developed an empirical Bayes method to recover chromatin structure from DNA, RNA, and protein abundance, allowing comparison of results from single-cell, bulk, and cell-free assays. Using single-cell multi-omic results, we show that the "surprise" value of an assay (the information yielded beyond that predicted from structure) is often context-dependent. The lens of chromatin structure thus focuses experimental design.
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