## 2 Materials and Methods
### Histone Modification Profile Preprocessing  
To apply the proposed method to histone modification profiles, individual histone modification profiles must share region index \(i\). Therefore, the amount of histone modification is averaged within shared regions that are generated by dividing the whole human or \begin{table}
\begin{tabular}{l} \hline \hline
**GEO IDs and descriptions** \\ \hline
**GSE24850** \\ \hline This study contained 11 H3K9 me3 ChIP-seq mouse nucleus accumbens experiments comprising six controls, three saline-treated samples, and two cocaine samples [16]. Among them, five controls and five treated samples were employed. Ten bed files that were provided as a Supplementary File in GEO were downloaded. One control sample with a GEO identification (ID) of GSM612984 was discarded, and the other ten samples were used. \\
**GSE159075** \\ \hline This study contained various histone modification ChIP-seq experiments using human umbilical vein endothelial cell lines [17]. Among them, three H3K4 me3 ChIP-seq, three H3K27 me3 ChIP, and three H3K27 ac ChIP-seq, as well as one input ChIP-seq profile, were employed. The corresponding 10 bigWig files were downloaded from the GEO Supplementary File. \\
**GSE74055** \\ \hline This study contained various histone modification ChIP-seq experiments using mouse E14 or DKO cell lines [18]. Among them, 16 H3K4 me1 ChIP-seq profiles and the corresponding 16 input profiles (32 profiles in total) were downloaded in the bigWig format provided in the GEO Supplementary File. \\
**GSE124690** \\ \hline This study comprised various histone modification CUT&Tag experiments using human H1 or K562 cell lines [19]. Among them, six bulk H3K4 me1 profiles (GSM3536499_H1_K4 me1_Rep1.bed.gz, GSM3536499_H1_K4 me1_Rep2.bed.gz, GSM3536516_K562_K4 me1_Rep2.bed.gz, GSM3680223_K562_H3K4 me1_Abcam_895.bed.gz, GSM3680224_K562_H3K4 me1_ActMot_39113.bed.gz), four bulk H3K3 me3 profiles (GSM3536501_H1_K4 me3_Rep1.bed.gz, GSM3536518_K562_K4 me3_Rep1.bed.gz, GSM3536518_K562_K4 me3_Rep2.bed.gz), and four bulk H3K27 ac profiles (GSM3536497_H1_K27 ac_Rep1.bed.gz, GSM3536497_H1_K27 ac_Rep2.bed.gz, GSM3536514_K562_K27 ac_Rep1.bed.gz, GSM3536514_K562_K27 ac_Rep2.bed.gz) were downloaded from the GEO Supplementary File. \\
**GSE188173** \\ \hline This study contained nine ChIP-seq H3K27 ac profiles (with one control and one treated with SPT) using patient–derived xenografts of human castration-resistant prostate cancer (18 profiles in total). The corresponding 18 bigWig files were extracted from the file GSE188173_RAW.tar retrieved from GEO Supplementary File. \\
**GSE159022** \\ \hline This study comprised four H3K4 me3 ChIP-seq profiles, four H3K27 me3 ChIP-seq profiles, and four H4K16 ac ChIP-seq profiles using mouse progenitor cells (two wild type (WT) and two neurofibromin knockouts) [20]. Among them, four H3K27 me3 profiles were used and four bigWig files were downloaded from the GEO Supplementary File. \\
**GSE168971** \\ \hline This study contained H3K27 ac and H3K9 ac ChIP-seq profiles taken from various experimental conditions [21], six H3K9 ac profiles using C3H-WT mouse liver, and two corresponding inputs were used. The corresponding eight bigWig files were downloaded from the GEO Supplementary File. \\
**GSE159411** \\ \hline This study comprised various ChIP-seq profiles [22]. Among them, four H3K36 me3 ChIP-seq profiles (two hiPSC cardiomyocytes and two WT hiPSCs) were used. The four corresponding bigWig files were downloaded from the GEO Supplementary File. \\
**GSE181596** \\ \hline This study consisted of four H3K27 me3 ChIP-seq profiles (two controls and two treatments) and four H3K4 me3 ChIP-seq profiles (two controls and two treatments) in addition to two input profiles that used cells as odontoblasts (treatment was siRNA: si-IKBz) [23]. Among them, four H3K27 me3 ChIP-seq profiles were downloaded from the GEO Supplementary File. \\ \hline \hline \end{tabular}
\end{table} 
Table 1: The list of histone modification profiles analyzed in this study.