## 3 Results  
### Overall Representation of Mutational Signatures  
This study first examined the prevalence of mutational signatures and cell subtype abundances in 25 TCGA tumor types using deconstructSigs and EPIC, respectively. Table 2 shows the average occurrence of mutational signatures across 25 tumor types, and Figure 2 presents the tumor type-specific profiles. Mutation signatures 16 and 1 were predominantly represented, as shown in Table 2, with mean values of 0.1335 and 0.1250, respectively. Next, tumor type-specific over- and underrepresented mutational signatures were investigated, and the representatives were substantially different. Mutational signatures 16 and 1 were widely represented in many tumor types, with values greater than 0.1 for 17 (BLCA, BRCA,ESCA, GBM, HNSC, KIRC, KIRP, LGG, LIHC, LUSC, PAAD, PCPG, PRAD, SARC, TGCT, THCA, THYM) and 12 tumor types (BRCA, CESC, COAD, ESCA, GBM, HNSC, LGG, PAAD, PRAD, READ, STAD, UCEC), respectively. Furthermore, the number of tumor types with maximal values for mutational signatures 16 or 1 was eight (ESCA, HNSC, KIRC, KIRP, LIHC, PCPG, THCA, THYM for signature 16; COAD, GBM, LGG, PAAD, PRAD, READ, STAD, UCEC for signature 1). However, signature 3 was the best for BRCA, OV, SARC, and TGCT, and signature 4 was the best for LUAD and LUSC. Signature 3 is related to BRCA1 and BRCA2 mutations, which are generally observed in breast and ovarian tumors [42; 43], whereas signature 4 is related to tobacco smoking [44]. Moreover, BLCA, CESC, and SKCM showed the best occurrence of signatures 13, 2, and 7, respectively, in contrast to other tumor types. Signatures 13 and 2 are known as APOBEC mutation signatures, whereas signature 7 is known as a UV signature.  
Next, the study investigated which genes were commonly mutated and which sequence alteration was mainly observed. Supplementary Figure S1 shows PCCs between the mutational signatures and the highly mutated top 20 genes, and Supplementary Figure S2 represents the correlation between the mutational signatures and the sequence alteration. As expected, tumor-related genes such as TP53, PIK3 CA, and KRAS were highly mutated in each tumor type, and the genes were positively correlated with certain mutational signatures. For example, in SKCM, signature 7 (UV signature) was the most representative (Figure 2), and the signature was positively correlated with most of the top 20 genes. However, this property was not observed in any of the tumor types. For instance, although GBM was overrepresented in signature 1 (aging signature), positively correlated genes among the top 20 genes were detected in signatures 10 and 14. When the genomic modifications  
\begin{table}
\begin{tabular}{c c} \hline \hline
**Mutational Signature** & **Average** \\ \hline Signature 1 & 0.1250 \\ Signature 2 & 0.0605 \\ Signature 3 & 0.0801 \\ Signature 4 & 0.0392 \\ Signature 5 & 0.0472 \\ Signature 6 & 0.0174 \\ Signature 7 & 0.0458 \\ Signature 8 & 0.0403 \\ Signature 9 & 0.0218 \\ Signature 10 & 0.0106 \\ Signature 11 & 0.0120 \\ Signature 12 & 0.0203 \\ Signature 13 & 0.0519 \\ Signature 14 & 0.0083 \\ Signature 15 & 0.0102 \\ Signature 16 & 0.1335 \\ Signature 17 & 0.0135 \\ Signature 18 & 0.0169 \\ Signature 19 & 0.0176 \\ Signature 20 & 0.0167 \\ Signature 21 & 0.0146 \\ Signature 22 & 0.0069 \\ Signature 23 & 0.0050 \\ Signature 24 & 0.0095 \\ Signature 25 & 0.0134 \\ Signature 26 & 0.0175 \\ Signature 27 & 0.0042 \\ Signature 28 & 0.0136 \\ Signature 29 & 0.0125 \\ Signature 30 & 0.0282 \\ \hline \hline \end{tabular}
\end{table}
Table 2: Average occurrence of mutational signatures across 25 tumor types.  
were examined, the amount of PCC was not identical to the representative signatures (Supplementary Figure S2).