Chromatin structure can introduce systematic biases in genome-wide analyses of Plasmodium falciparum

Background: The maintenance, regulation, and dynamics of heterochromatin in the human malaria parasite, Plasmodium falciparum, has drawn increasing attention due to its regulatory role mutually exclusive virulence gene expression silencing key developmental regulators. The advent genome-wide analyses such as chromatin-immunoprecipitation followed by sequencing (ChIP-seq) been instrumental understanding chromatin composition; however, even model organisms, ChIP-seq experiments are susceptible intrinsic experimental biases arising from underlying structure. Methods: We performed a control experiment, re-analyzed previously published datasets compared different analysis approaches characterize P. falciparum. Results: We found that heterochromatic regions input samples used for normalization systematically underrepresented regard coverage across falciparum genome. This underrepresentation, combination with non-specific or inefficient immunoprecipitation, can lead identification false enrichment peaks these regions. observed also be seen at background levels specific efficient experiments. further report on how read mapping skew within highly similar subtelomeric families. To ameliorate issues, we discuss orthogonal methods bona fide chromatin-associated proteins. Conclusions: Our results highlight impact structure parasite need caution when characterizing chromatin-associated proteins features.