MAnorm: ChIP-Seq data quantitative comparison

ChIP-Seq is widely used to characterize genome-wide binding patterns of transcription factors and other chromatin-associated proteins. Although comparison of ChIP-Seq data sets is critical for understanding cell type-dependent and cell state-specific binding, and thus the study of cell-specific gene regulation, few quantitative approaches have been developed. Here, we present a simple and effective method, MAnorm, for quantitative comparison of ChIP-Seq data sets describing transcription factor binding sites and epigenetic modifications. The quantitative binding differences inferred by MAnorm showed strong correlation with both the changes in expression of target genes and the binding of cell type-specific regulators.

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Motif-Scan: scan genomic regions for target of given motifs and perform enrichment analysis

(Under Constuction. Please Ignore) With the accumulation of ChIP-seq data across different cell types, an effective and accurate method are essential to unravel the relationship between regulator binding and epigenetic modifications in different cell types. We present an integrative computational toolkit, MAmotif, to infer cell type specific regulators. Based on a hypotheses that the regions with higher epigenetic changes are more likely to be directly targeted by key cell type specific regulators, we combine MAnorm’s quantitative comparison information of 2 cell types and transcription factor binding sites information to infer cell type specific regulators. Here MAnorm is a model for quantitative comparison of ChIP-seq data between 2 cell types. While TFBS are detected from the epigenetic change regions by our newly developed motif scanning package. Our motif scan algorithm is a probabilistic model based on position weight matrix (PWM): the score of motif A is calculated as the ratio of A’s probability of occurrence on the target sequence and its probability of occurrence on the genome background. The target sequence can finally be defined as the motif A target sequence when the score is beyond the score threshold, which is from the distribution of motif A scores calculated on the whole genome sequence. When the epigenetic modification changes and TFBS information are prepared, several statistical tests and clustering methods are applied to determine the linkage between epigenetic modification changes and the motif binding affinity in specific cell type. To validate the effectiveness of MAmotif, the toolkit are performed on the two cell lines —— H1ESC vs K562, two transcription factor: SOX2 and POU5f1 are detected as the H1ESC-specific regulators, which is consistent with previous report.

MAmotif: an integrative toolkit for searching cell type-specific co-factors associated with differential binding

(Under Constuction. Please Ignore) With the accumulation of ChIP-seq data across different cell types, an effective and accurate method are essential to unravel the relationship between regulator binding and epigenetic modifications in different cell types. We present an integrative computational toolkit, MAmotif, to infer cell type specific regulators. Based on a hypotheses that the regions with higher epigenetic changes are more likely to be directly targeted by key cell type specific regulators, we combine MAnorm’s quantitative comparison information of 2 cell types and transcription factor binding sites information to infer cell type specific regulators. Here MAnorm is a model for quantitative comparison of ChIP-seq data between 2 cell types. While TFBS are detected from the epigenetic change regions by our newly developed motif scanning package. Our motif scan algorithm is a probabilistic model based on position weight matrix (PWM): the score of motif A is calculated as the ratio of A’s probability of occurrence on the target sequence and its probability of occurrence on the genome background. The target sequence can finally be defined as the motif A target sequence when the score is beyond the score threshold, which is from the distribution of motif A scores calculated on the whole genome sequence. When the epigenetic modification changes and TFBS information are prepared, several statistical tests and clustering methods are applied to determine the linkage between epigenetic modification changes and the motif binding affinity in specific cell type. To validate the effectiveness of MAmotif, the toolkit are performed on the two cell lines —— H1ESC vs K562, two transcription factor: SOX2 and POU5f1 are detected as the H1ESC-specific regulators, which is consistent with previous report.