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Abstract:
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Assays capable of detecting genome-wide chromatin interactions have produced massive amount of data and led to great understanding of the chromosomal three-dimensional (3D) structure. As technology becomes more sophisticated, higher resolution data are being produced, going from the initial 1 Mb to the current 10 Kb resolution. The availability of genome-wide data necessitates development of analytical methods to recover the underlying 3D structure, but challenges abound. Most methods were proposed for analyzing data at low resolution; their behaviors are thus unknown for higher resolution data, which has the ubiquitous feature of excess of zeros. To this end, we propose a truncated Random effect EXpression (tREX) method that can handle data at various resolutions. To assess the performance of tREX and a number of leading existing methods for recovering the underlying chromatin structure, we created in-silico data to mimic multiple levels of resolution and submit the methods to the "stress test". We also applied tREX and the comparison methods to a Hi-C dataset, for which Fluorescence In Situ Hybridization (FISH) measurements are available, to substantiate estimation accuracy.
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