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Fig. 1 | Genome Biology

Fig. 1

From: BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes

Fig. 1

Description of BaalChIP model. a The basic inputs for Baal are the ChIP-seq raw read counts in a standard BAM alignment format, a BED file with the genomic regions of interest (such as ChIP-seq peaks), and a set of heterozygous SNPs in a tab-delimited text file. Optionally, genomic DNA BAM files can be specified for RAF computation. Alternatively, the user can specify the pre-computed RAF scores for each variant. b The first module of BaalChIP consists of (1) computing allelic read counts for each heterozygous SNP in peak regions and (2) a round of filters to exclude heterozygous SNPs that are susceptible to generating artifactual ASB effects. (3) The reference mapping (RM) bias and the reference-allele frequency (RAF) are computed internally and the output consists of a data matrix where RM and RAF scores are included alongside information about allele counts for each heterozygous SNP. The column Peak contains binary data to indicate the called peaks. c The second module of BaalChIP consists of calling ASB binding events. (4) BaalChIP uses a beta-binomial Bayesian model to consider RM and RAF bias when detecting ASB events. d The output from BaalChIP is a posterior distribution for each SNP. A threshold to identify SNPs with allelic bias is specified by the user (default value is a 95% interval). (5) The output of BaalChIP is a credible interval (lower and upper) calculated based on the posterior distribution. This interval corresponds to the true AR in read counts (i.e., after correcting for RM and RAF biases). An ASB event is called if the lower and upper limits of the interval are outside the 0.4–0.6 interval. Alt alternative, AR allelic ratio, ASB allelic-specific binding, gDNA genomic DNA, Het. heterozygous, MAPQ, mapping quality, NA not applicable, RAF reference-allele frequency, Ref reference, Rep repeat, RM reference mapping, SNP single-nucleotide polymorphism, TF transcription factor

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