Methods for ChIP-seq Normalization and Their Application for the Analysis of Regulatory Elements in Brain Cells

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has become one of the major tools to elucidate gene-expression regulation. Similar to other molecular profiling methods, ChIP-seq is sensitive to several technical biases which affect downstream results, especially in cases when material quality is difficult to control, for example, frozen post-mortem human tissue. However, methods for bioinformatics analysis improve every year and allow the mitigation of these effects after sequencing by adjusting for both technical ChIP-seq biases and more general biological biases like postmortem interval or cell heterogenity of the sample. Here we review a wide selection of ChIP-seq normalization methods with a focus on application in specific experimental settings, in particular when brain tissue is investigated.