Next generation sequencing (NGS) technologies have been used in diverse ways to investigate facets of chromatin biology by identifying genomic loci that are bound by transcription factors, occupied by nucleosomes, accessible to nuclease cleavage, or physically interact with remote genomic loci. Reaching sound biological conclusions from such NGS enrichment profiles, however, requires that many potential biases be taken into account. In this Review we discuss common ways in which bias may be introduced into NGS chromatin profiling data, ways in which these biases can be diagnosed, and analytical techniques to mitigate their effect.
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