Table 1.
Details of sequence, epigenetic and structural features that can be included in the MutSpot model.
| Feature | Feature detail | Rationale | Source |
|---|---|---|---|
| Sequence context (SNVs) | Identity of mutated base (A/T or C/G). Trinucleotide and penta-nucleotide contexts centered at the mutated base, and 1 bp and 2 bp left and right flanks of the mutated base. | Sequence context is a major covariate of mutation probability. Although previous studies typically considered trinucleotide contexts, mutation rates could be affected by wider sequence contexts25. | Computed from mutation data |
| Sequence context (indels) | Presence of poly-A/T or poly-C/G sequences longer than 5 bp at the indel site. | Long mononucleotide repeats could lead to artifacts in indel calling. | Computed from mutation data |
| TF-binding profiles | ChIP-Seq peak profiles of 132 TFs and 1 meta profile including peaks of all TFs from ENCODE cell lines. | TF-binding sites have elevated mutation rates in certain cancers due to impaired nucleotide excision repair. | Zerbino et al. 26 |
| Replication timing | Mean replication timing profile of 13 ENCODE cell lines. | Replication timing is inversely correlated with mutation probability. | Hansen et al. 27 |
| APOBEC editing sites | Predicted APOBEC editing sites. | Elevated mutation rates at APOBEC editing sites could lead to the formation of passenger hotspots. | Buisson et al.28 Table S2. |
| Local mutation rate | Mutation rate of 100 kb nonoverlapping genomic bins. | To correct for additional unexplained regional variation in mutation rates. | Computed from mutation data |
| Individual mutation count | Mutation burden of individual tumors. | To account for intertumor heterogeneity. | Computed from mutation data |
| Tissue-specific epigenetic profile | Chromatin accessibility and modification profiles from matched tissue/cell type. | Epigenetic profiles from the cell of origin better predict the mutational landscape of tumors13. | Supplied by the user |
| COSMIC mutation signatures | Proportion of mutations contributed by a specific mutation signature for each tumor. | To further correct for specific mutational processes in the tumor cohort. | Supplied by the user |